JKAP serves as a potential biomarker for the evaluation of inflammatory condition, disease activity, and treatment response to TNF inhibitor in ankylosing spondylitis patients.

OBJECTIVE: This study aimed to evaluate the value of JKAP as a biomarker in estimating treatment response to TNF inhibitor in AS patients. METHODS: Totally, 63 AS patents who planned to receive adalimumab (TNF inhibitor) treatment were enrolled. Baseline JKAP level was determined in serum samples. All patients received 40 mg adalimumab every two weeks for 12 weeks. At W2, W4, W8, and W12, ASAS40 response rates were evaluated. RESULTS: JKAP was negatively correlated with CRP (P = 0.032), BASDAI score (P = 0.021), BASFI score (P = 0.045), ASDASCRP score (P = 0.038), TNF-α (P = 0.031), IL-6 (P = 0.025) and IL-17A (P = 0.022). The ASAS40 response rates were 17.5%, 31.7%, 44.4% and 55.5% at W2, W4, W8 and W12, respectively. Baseline JKAP level was lower in patients with ASAS40 response than those without ASAS40 response (25.8 (13.2-42.7) pg/mL vs. 47.3 (26.7-71.2) pg/mL, P = 0.003). Multivariate logistic regression disclosed that JKAP level (P = 0.049) and CRP level (P = 0.014) independently correlated with ASAS40 response; further analyses disclosed that they exhibited acceptable to good ability in distinguishing patients with ASAS40 response from those without ASAS40 response. CONCLUSION: JKAP serves as a potential biomarker for evaluation of inflammatory condition, disease activity, especially for assessing treatment response to TNF inhibitor in AS patients.

Long noncoding RNA intersectin 1-2 gradually declines during adalimumab treatment, and its reduction correlates with treatment efficacy in patients with ankylosing spondylitis.

Previous studies show that long noncoding RNA intersectin 1-2 (lnc-ITSN1-2) promotes the inflammation process and serves as a potential biomarker in autoimmune diseases, except for ankylosing spondylitis (AS). Therefore, this study aimed to explore the correlation of baseline lnc-ITSN1-2 expression with disease risk and activity of AS, and to investigate its longitudinal change with treatment response to a tumour necrosis factor alpha (TNFα) inhibitor in patients with AS. In total, 63 patients with AS receiving 12-week adalimumab treatment were included and their baseline clinical features were collected. Lnc-ITSN1-2 expression in peripheral blood mononuclear cells (PBMC) of patients with AS was detected by reverse transcription quantitative polymerase chain reaction. Meanwhile, Assessment in Spondyloarthritis International Society (ASAS) 40 response was evaluated at week 2 (W2), W4, W8, and W12. According to the ASAS40 response status at W12, patients with AS were classified into responders and non-responders. PBMC lnc-ITSN1-2 expression was also determined in healthy controls (N = 60). Lnc-ITSN1-2 expression was elevated in patients with AS compared to controls (P < 0.001). Baseline lnc-ITSN1-2 expression was positively associated with C-reaction protein (CRP) (P = 0.021), interleukin (IL)-1ß (P = 0.020), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score (P = 0.040), and Ankylosing Spondylitis Disease Activity score with C-reactive protein (ASDASCRP) (P = 0.045) in patients with AS. Furthermore, lnc-ITSN1-2 expression declined during the treatment with adalimumab (P < 0.001). Notably, this reduction was more obvious in responders than non-responders. In conclusion, declined lnc-ITSN1-2 expression during the TNFα inhibitor treatment correlates with good treatment efficacy in patients with AS, suggesting its clinical value for AS management.

Oral Nickel Changes of Intestinal Microflora in Mice.

Nickel, a silver-colored metal found in nature, is a common cause of allergic contact dermatitis. Nevertheless, the existence of inflammatory reaction to oral nickel exposure remains controversial. The following study investigates whether oral nickel can change the intestinal microflora in mice. A total of 20 female ICR mice were randomly divided into two groups: the oral nickel group (Group O) and the control group (Group C). Group O received water containing 400 µM NiSO4·6H2O, while group C was given pure water for 21 days. The content of nickel in the kidneys was determined by atomic absorption spectrophotometry, while the composition of bacterial community in the cecum was detected by 16S rDNA sequencing. The results were subsequently validated by real-time quantitative PCR with genus and species specific primers. Compared to Group C, significantly higher nickel levels were observed in Group O (P = 0.016); however, our data suggested that oral administration of 400 µM NiSO4·6H2O was nontoxic to the animals. (No statistical difference in body animal weight was found between Group O and Group C, before and after oral administration of nickel.) At the genus level, significantly higher relative abundance of Bacteroides (P = 0.016) and Intestinimonas (P = 0.018), and significantly lower relative abundance of Lachnospiraceae_NK4A136_group (P = 0.002) and Lachnospiraceae_UCG-001_group (P = 0.042) were observed in the oral nickel group compared to the control group. In addition, Group O had significantly lower ratio of Firmicutes/Bacteroides (P = 0.008). The results of real-time quantitative PCR further confirmed that the amplicon mass of Bacteroides and B. fragilis in the Group O was significantly higher compared to C group (P = 0.034 and P = 0.02). Oral nickel could change the intestinal microflora in mice, thus suggesting that oral nickel alters the interaction between the host and the intestinal flora.

Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury.

Spinal cord injury (SCI) is a severe central nervous system disease, which may cause serious locomotor deficit. Acacetin is a flavone that possesses antioxidant and anti-inflammatory effects in different human diseases. The main purpose of this study was to explore whether acacetin ameliorates SCI in mice. A model of SCI was established in C57BL/6 mice. The Basso Mouse Scale (BMS) score, BMS subscore, mechanical hypersensitivity, and thermal hypersensitivity of mice were tested for determining the motor function. Immunofluorescence staining was utilized to detect NeuN, GFAP, and Iba-1 levels in spinal cord tissues. ELISA was utilized to assess the contents of proinflammatory factors such as interleukin (IL)-1ß, IL-18, and tumor necrosis factor-alpha (TNF-α) in spinal cord tissues. The levels of oxidative stress markers, reactive oxygen species, thiobarbituric acid-reactive substances, superoxide dismutase, catalase, glutathione peroxidase, and glutathione were detected using their corresponding kits. Western blot was employed for estimating the levels of heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap-1). In this study, acacetin treatment recovered the motor function in SCI mice. Acacetin improved neuron integrity and repressed glial cell activation in the spinal cord tissues of SCI mice. Furthermore, acacetin administration reduced the SCI-induced high concentrations of IL-1ß, IL-18, and TNF-α, as well as inhibited oxidative stress in SCI mice. Moreover, acacetin activated HO-1/Nrf2 pathway in SCI mice. The neuroprotective effects of acacetin against SCI were reversed by Nrf2 inhibitor. Overall, acacetin alleviated neuroinflammation and oxidative stress injury by activating the Nrf2/HO-1 signaling pathway in the mouse models of SCI.

Systemic Contact Dermatitis: The Routes of Allergen Entry.

Systemic contact dermatitis (SCD) is a generalized reactivation of type IV hypersensitivity skin diseases in individuals with previous sensitization after a contact allergen is administered systemically. Patients with SCD may consider their dermatitis unpredictable and recalcitrant since the causative allergens are difficult to find. If a patient has a pattern of dermatitis suggestive of SCD but fails to improve with conventional treatment, SCD should be taken into consideration. If doctors are not familiar with the presentations of SCD and the possible routes of allergen sensitization and exposure, the diagnosis of SCD may be delayed. In this work, we summarized all of the routes through which allergens can enter the body and cause SCD, including oral intake, local contact (through skin, inhalation, nasal spray and anal application), implants, and other iatrogenic or invasive routes (intravenous, intramuscular, intraarticular, and intravesicular). This will provide a comprehensive reference for the clinicians to identify the culprit of SCD.

Efficacy of Artesunate against Pseudomonas aeruginosa Biofilm Mediated by Iron.

Pseudomonas aeruginosa is capable of causing a variety of chronic infections due to the formation of biofilms. Iron is essential for growth of Pseudomonas aeruginosa, and therapies that interfere with iron may help treat P. aeruginosa infections. Herein, we investigated whether artesunate, which is a type of iron-dependent drug, could influence Pseudomonas aeruginosa biofilm formation and structure, including the underlying mechanisms. Artesunate could enhance twitching motility significantly and decrease the proportion of surviving cells in Pseudomonas aeruginosa biofilms in a dose-dependent manner. Artesunate treatment also reduced biofilm thickness, diffusion in the biomass, and the content of Fe(II). However, changes in biofilm structure and ion concentration were very similar following treatment with 512 µg/ml and 1024 µg/ml artesunate. Interestingly, both biofilm structure and surviving cell fraction were recovered after iron supplementation. These results suggest that artesunate interferes with Pseudomonas aeruginosa biofilms by decreasing bacterial viability and enhancing twitching motility in an iron-independent manner.

Analysis of nickel distribution by synchrotron radiation X-ray fluorescence in nickel-induced early- and late-phase allergic contact dermatitis in Hartley guinea pigs.

BACKGROUND: Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy. METHODS: Forty Hartley guinea pigs were divided into four groups according to the NiSO4 sensitizing concentration and the NiSO4 challenged concentration: the 5% NiSO4-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO4-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-µ-XRF) and micro X-ray absorption near-edge spectroscopy (µ-XANES). RESULTS: In each section, the nickel element concentration in both the 5% NiSO4-group and 10% NiSO4-group was significantly higher than that in the negative control group. In the upper 300-µm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (>200 µm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-µ-XRF. According to the XANES data for the 10% NiSO4 metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni aqueous ionic state but in the nickel-binding protein. CONCLUSIONS: This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.

[A Method Research on Environmental Damage Assessment of a Truck Rollover Pollution Incident].

With high occurrence of sudden water pollution incident, China faces an increasingly severe situation of water environment. In order to deter the acts of environmental pollution, ensure the damaged resources of environment can be restored and compensated, it is very critical to quantify the economic losses caused by the sudden water pollution incident. This paper took truck rollover pollution incidents in Chongqing for an example, established a set of evaluation method for quantifying the environmental damage, and then assessed the environmental damage by the method from four aspects, including the property damage, ecological environment and resources damages, the costs of administrative affairs in emergency disposal, and the costs of investigation and evaluation.