Emerging Role of Interleukin-38 (IL-38) in the Development of Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. METHODS: In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups-low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)-using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1ß, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. RESULTS: At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1ß significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1ß among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1ß exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. CONCLUSION: IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.

Transcriptomic Profiling of Tomato Leaves Identifies Novel Transcription Factors Responding to Dehydration Stress.

Drought is among the most challenging environmental restrictions to tomatoes (Solanum lycopersi-cum), which causes dehydration of the tissues and results in massive loss of yield. Breeding for dehydration-tolerant tomatoes is a pressing issue as a result of global climate change that leads to increased duration and frequency of droughts. However, the key genes involved in dehydration response and tolerance in tomato are not widely known, and genes that can be targeted for dehydration-tolerant tomato breeding remains to be discovered. Here, we compared phenotypes and transcriptomic profiles of tomato leaves between control and dehydration conditions. We show that dehydration decreased the relative water content of tomato leaves after 2 h of dehydration treatment; however, it promoted the malondialdehyde (MDA) content and ion leakage ratio after 4 h and 12 h of dehydration, respectively. Moreover, dehydration stress triggered oxidative stress as we detected significant increases in H2O2 and O2- levels. Simultaneously, dehydration enhanced the activities of antioxidant enzymes including peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and phenylalanine ammonia-lyase (PAL). Genome-wide RNA sequencing of tomato leaves treated with or without dehydration (control) identified 8116 and 5670 differentially expressed genes (DEGs) after 2 h and 4 h of dehydration, respectively. These DEGs included genes involved in translation, photosynthesis, stress response, and cytoplasmic translation. We then focused specifically on DEGs annotated as transcription factors (TFs). RNA-seq analysis identified 742 TFs as DEGs by comparing samples dehydrated for 2 h with 0 h control, while among all the DEGs detected after 4 h of dehydration, only 499 of them were TFs. Furthermore, we performed real-time quantitative PCR analyses and validated expression patterns of 31 differentially expressed TFs of NAC, AP2/ERF, MYB, bHLH, bZIP, WRKY, and HB families. In addition, the transcriptomic data revealed that expression levels of six drought-responsive marker genes were upregulated by de-hydration treatment. Collectively, our findings not only provide a solid foundation for further functional characterization of dehydration-responsive TFs in tomatoes but may also benefit the improvement of dehydration/drought tolerance in tomatoes in the future.

Development of a vibrotactile cueing device that implicitly increases walking speed during gait training in stroke patients: an observational case series study.

One of the main sequelae of stroke is difficulty walking, which is characterised by decreased walking speed and asymmetrical walking patterns. Physical therapists often rely on explicit motor learning strategies, i.e., providing mainly verbal instructions for how movements should be performed. However, the voluntary movement induced by explicit instruction may lead to associated unintended muscle contractions or higher cognitive demand, which could be detrimental. We introduce a vibrotactile cueing device that implicitly improves walking speed. The stroke patient walks while alternating vibrational cues are given to the left and right sides of their waist. At each specified step, cueing frequency increases in the cueing group without the patient's awareness. The four patients in the cueing group did not notice the increase in walking speed during training; however, we observed an improvement in walking speed and cadence in patients using the proposed cueing system, which was maintained during the posttest phase. Additionally, patients using the cueing system were able to suppress excessive compensatory movements during training compared with patients who did not use the system. This case series study indicates that the proposed system for gait rehabilitation of stroke patients can enable an increase in walking speed without excessive effort.

Investigation of optimal gait speed for motor learning of walking using the vibro-tactile biofeedback system.

In stroke patients, sensory loss often reduces the sensation of ground contact, which impairs motor learning during rehabilitation. In our previous study, we proposed a vibro-tactile biofeedback system (which we called the perception-empathy biofeedback system) for gait rehabilitation. The results of our 9-week pilot clinical test suggested that patients who had reached the autonomous phase in gait learning had difficulty noticing the external vibratory feedback provided by the biofeedback system, leading to ineffective intervention. We considered the possibility that slower walking speed might return the patient to the association phase and allow patients to improve their gait according to the sensory feedback provided. Thus, in this research, a method based on reducing walking speed to guide patients' attention was derived. A pilot clinical trial shows that there is a statistically significant increase of ankle dorsiflexion in the initial contact phase and increase of ankle plantarflexion in the push-off phase after vibro-tactile biofeedback system intervention with speed reduction, compared to intervention without speed reduction. The results suggest that, by reducing their walking speed during intervention, patients return to the association phase and recognize external vibratory feedback, which may result in better intervention effects.Clinical Relevance-This study provides knowledge about the optimal walking speed when using vibro-tactile biofeedback for motor learning in stroke patients.

A Haptic-Based Perception-Empathy Biofeedback System with Vibration Transition: Verifying the Attention Amount.

In this paper, a perception-empathy biofeedback (PEBF) system is proposed that supplements the foot pressure status of a paralyzed foot with a wearable vibrotactile biofeedback (BF) vest to the back. Improvements in the ankle dorsiflexion and push-off movement in the swing phase and pre-swing phase, respectively, can be expected after using the proposed system. However, the results of the 3 week pilot clinical tests suggest that significant improvement is only observed for the push-off movement. It is assumed that the attention required to recognize the BF was beyond the ability of the patients. In this paper, a dual task (40 s walking and performing mental arithmetic at the same time) was conducted with the following conditions: no vibrations and providing BF to the lower back and the entire back. According to the results, the ankle joint angle of the paralyzed side at push-off under the entire back condition is statistically significant (p = 0.0780); however, there are no significant changes under the lower back condition (p = 0.4998). Moreover, the ankle joint angle of the paralyzed side at the initial contact is statistically significant with respect to the lower back condition (p = 0.0233) and shows a significant trend for the entire back condition (p = 0.0730). The results suggest that the limited attention capacity of hemiplegic patients fails to improve both dorsiflexion and push-off movements; moreover, ankle motion can be promoted if attention is concentrated on recognizing focalized vibratory feedback patterns.