High-throughput RNA-sequencing reveals novel targets of tofacitinib in the treatment of rheumatoid arthritis.

OBJECTIVES: Although tofacitinib has been confirmed to have good efficacy and safety in the treatment of rheumatoid arthritis (RA), the relevant mechanism at the whole transcriptome level has not yet been revealed. In this study, peripheral blood mononuclear cells (PBMCs) from patients with active RA before and after tofacitinib treatment were analysed using whole transcriptome sequencing technology. METHODS: Fourteen patients with active RA were selected to detect the alterations of mRNAs, lncRNAs, circRNAs, and miRNAs in PBMCs before and after tofacitinib treatment using whole transcriptome sequencing. Through bioinformatics analysis, differentially expressed RNAs and their functions were identified. Then the competitive endogenous RNA (ceRNA) network and the protein interaction network were constructed. And qRT-PCR validation was performed for RNAs in the ceRNA network. RESULTS: Based on 69 DEmRNAs, 1743 DElncRNAs, 41 DEcircRNAs, and 4 DEmiRNAs obtained from whole transcriptome sequencing, an RNA interaction network including mRNA DEPDC1, lncRNA ENSG00000272574, circRNA hsa_circ_0034415, miR-190a-5p, and miR-1298-5p was constructed according to ceRNA theory. The qRT-PCR validation results of DEPDC1, hsa_circ_0034415 and miR-1298-5p involved in the network were consistent with the sequencing results, which provided important research evidence for further study of these RNAs. CONCLUSIONS: The new discovered circRNA/lncRNA-miRNA-mRNA network in RA patients relevant to tofacitinib therapy will provide new enlightenment for the role of tofacitinib in the treatment of RA and shed light on a new direction for further exploring the deep-seated mechanism of this drug.

Revealing the changes in signaling pathways caused by tofacitinib in patients with rheumatoid arthritis through RNA sequencing and the correlation with clinical parameters.

OBJECTIVES: The current study is to accelerate the understanding of how tofacitinib works in patients with rheumatoid arthritis (RA) due to the lack of relevant information. METHOD: We selected ten patients with active RA and obtained the expression profile for their peripheral blood mononuclear cells before and after the tofacitinib treatment by RNA sequencing. The gene set enrichment analysis was conducted, and the significantly enriched gene sets were identified. The hub gene highly correlated with clinical parameters in the gene set was selected. We constructed the weighted gene co-expression network, linked modules with clinical indicators, and screened hub genes. The expression of representative hub genes was validated by real-time quantitative PCR (qPCR). RESULTS: Gene set interferon (IFN) α and IFN ß signaling was the most significantly down-regulated after tofacitinib treatment. In this gene set, genes Oas2 and Oasl showed a significant positive correlation with morning stiffness. In co-expression network, gene Vgll3 from the violet module with the highest correlation coefficient, was positively correlated with morning stiffness. Among them, Oasl and Vgll3 have shown significant down-regulation in qPCR validation. CONCLUSIONS: Our results highlighted the role of type I IFN, mainly including IFN α and IFN ß, in the pathogenesis of RA and action for tofacitinib, and provided a new entry point for further elucidating the mechanism of morning stiffness. Key Points • Gene set IFN α and IFN ß signaling was the most significantly down-regulated after tofacitinib treatment in RA patients. • Gene Oasl and Vgll3 were correlated with morning stiffness and significantly down-regulated due to the action of tofacitinib. • Type I IFN system was highlighted in the action of tofacitinib.

Effects of different drying methods on chemical compositions, antioxidant activity and anti-α-glucosidase activity of Coreopsis tinctoria flower tea.

Coreopsis tinctoria (CT) flower is widely consumed as flower tea with many good healthcare benefits in China, and room drying is the most common drying method of CT, while many rapid and controllable modern instrument drying methods have been used for the drying of flowers teas. In the present study, effects of drying methods on chemical components, antioxidant activity and anti-α-glucosidase activity of CT have been compared to search for proper drying methods. In the results, drying methods have significant effects on the chemical composition, antioxidant activity and anti-α-glucosidase activity of CT. Vacuum drying at 50 °C, hot air drying at 30 °C and hot air drying at 50 °C are the top three drying methods to produce dried CT of high quality, and hot air drying at 30 °C is more energy-efficient and time-saving. Our results provide some new choices for CT in the future.

Effects of acupuncture treatment on posttraumatic headache after traumatic brain injury in patients: A protocol for systematic review.

BACKGROUND: Posttraumatic headache (PTH) after traumatic brain injury (TBI) is a common clinical symptom, which refers to a headache that occurs after TBI. Acupuncture is often used for the treatment of such patients in China, and significant clinical effects have been achieved. However, to date, its efficacy has not been methodically evaluated. The purpose of this systematic review is to provide evidence to prove the effectiveness of acupuncture in the treatment of PTH in patients with TBI. METHODS: This systematic review will be conducted in accordance with the preferred reporting items for systematic review and meta-analysis protocols. The following electronic databases will be searched from their inception to February 2022: PubMed, Web of Science, Embase, PsycINFO, the Cochrane Library, and Chinese databases such as Chinese Biomedical Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database, and China National Knowledge Infrastructure (CNKI). No language restrictions will be applied to the search strategy. Randomized controlled trials and cohort and case-control studies that met the inclusion and exclusion criteria will be included in this study. The meta-analysis will be performed using RevMan 5.3 software. Each session of this systematic review will be conducted independently by 2 members. RESULTS: This review evaluates the efficacy of acupuncture in the treatment of PTH after TBI. CONCLUSION: This review provides substantial evidence for the clinical application of acupuncture in PTH treatment after TBI. ETHICS AND DISSEMINATION: Since the data in this study will be retrieved from published trials, therefore the Patient Consent Statement and Ethical Approval are not required. We will disseminate our results by publishing the research in a peer-reviewed journal. TRAIL REGISTRATION NUMBER: The protocol was registered in INPLASY (INPLASY 202220073).

[Hierarchical structure of Five-shu points and Source-point of Triple Energizer Meridian in rabbits].

OBJECTIVE: To study the position and hierarchical structure of Five-shu points, i．e., "Guanchong" (TE1), "Yemen" (TE2), "Zhongzhu" (TE3), "Yangchi" (TE4) and "Zhigou" (TE6), and the Source-point "Tianjing" (TE10) of the Triple Energizer (TE) Meridian in the rabbit. METHODS: Based on WHO Standard Acupuncture Point Locations in the Western Pacific Region (WHO Standard) and National Standard (GB/T 22103-2008) for Acupuncture Point Locations in human body, and combined with X-ray images, the hierarchical structure of Five-shu points and Source-point of the TE Meridian were observed in ten New Zealand rabbits. The acupoint locations were determined by comparing the same name tissues of the rabbits and human body after dissecting the above-mentioned acupoints. After inserting acupuncture needles into the aforementioned acupoints, the relationship between the acupuncture needle and adjacent structure were dissected and measured. RESULTS: "Guanchong" (TE1) was located on the lateral side of the 4th terminal phalanx, and behind the corner of the onyx root. When needled, the penetrated tissues of the acupuncture needle are skin, superficial fascia, deep fascia, and the root region of the 4th phalanx, respectively. "Yemen" (TE2) was located between the 4th and 5th onyxes, at the depression of intersection of coat hair superior to the fingerweb edge. When needled, the penetrated tissues of the acupuncture needle are the superficial fascia, deep fascia and lumbrical muscles of the forepaw, respectively. "Zhongzhu" (TE3) was located between the 4th and 5th metacarpal bones, at the depression proximal to the 4th metacarpophalangeal joint. When needled, the penetrated tissues are skin, superficial fascia, deep fascia, and lumbrical muscle, respectively. "Yangchi" (TE4) was positioned at the dorsal side of the forepaw, and the surface connection line between the accessory and radial bones intersected with the depression of the extensor digitorum communis on the ulnar side. When needled, the penetrated tissues are skin, superficial fascia, deep fascia, and the ulnar side of the common extensor tendon, respectively. "Zhigou" (TE6) was positioned between the radius and ulna, on the posterior aspect of the forelimb and 3 Bone-cun proximal to the distal dorsal forepaw crease. When needled, the penetrated tissues are skin, superficial fascia, deep fascia, and the extensor digitorum, respectively. "Tianjing" (TE10) was located at the junction of the body of humerus and the lateral condyle of humerus, on the posterior aspect of the elbow and proximal to the prominence of the olecranon. When needled, the penetrated tissues are skin, superficial fascia, deep fascia, and triceps brachii muscle, respectively. CONCLUSION: The Five-shu points and Source-point of the TE Meridian on the forelimb in rabbits are innervated by the cutaneous branches of the ulnar radial nerve and the medial brachial cutaneous nerve at the superficial layer, and by the branches of the ulnar nerve and radial nerve in the deep layer, accompanied with cephalic vein and forearm blood vessels and their branches.

Bioavailability of cadmium to celery (Apium graveolens L.) grown in acidic and Cd-contaminated greenhouse soil as affected by the application of hydroxyapatite with different particle sizes.

Cadmium contamination in greenhouse vegetable fields greatly limited the sustainable production especially of leafy vegetables. Hydroxyapatite (HAP), as a common soil amendment, has been widely used in the remediation of Cd-contaminated soils, while its remediation efficiency greatly depends on its particle sizes. In this study, a rhizobag pot experiment was conducted to investigate the effects of HAP (<60 nm, <12 µm and <80 µm) on bioavailability of Cd to celery grown in acidic and slightly Cd-contaminated greenhouse soil. The results suggested that HAP with the largest particle size (<80 µm) had the best effectiveness in reducing Cd uptake especially by the edible part of celery. Specifically, the increase in HAP (<80 µm) addition from 0.5% to 3% prominently reduced Cd concentrations in celery shoot by 19.6%-76.8% as compared with the untreated group. Also, adding HAP (<80 µm) especially at 3% significantly decreased translocation factor (TF) of Cd from celery root to shoot by 30.6% and reduced bioconcentration factor (BCF) of Cd from rhizosphere soil to celery shoot by 76.4%. These were predominantly associated with the significantly increased soil pH and the subsequently decreased soil CaCl2-Cd concentration after adding HAP (<80 µm). Overall, although rhizosphere soil pH was the key factor in controlling Cd uptake by edible celery and regulating BCF and TF of Cd, insignificant root-induced acidification had limited effect on the immobilization efficiency of Cd by HAP (<80 µm). In conclusion, HAP (<80 µm) has good potential for the remediation of Cd-contaminated greenhouse soils.

Using pXRF to assess the accumulation, sources, and potential ecological risk of potentially toxic elements in soil under two greenhouse vegetable production systems in North China.

Intensive greenhouse vegetable production (GVP) has increased the pollution risk of potentially toxic elements (PTEs) in soils. This study examined the accumulation, sources, and potential ecological risk of six PTEs (Cu, Zn, As, Ni, Pb, and Cr) in soil under two GVP (solar greenhouse (SG) and round-arched plastic greenhouse (RAPG)) systems by portable X-ray fluorescence spectroscopy (pXRF) and conventional laboratory analysis. The results indicated that all PTE concentrations were lower than their corresponding thresholds in GVP soils, presenting a low potential ecological risk in both GVP soils according to risk indices (RI ≤ 40.67). As, Ni, Pb, and Cr were not significantly accumulated in both GVP soils. Although Cu and Zn accumulated in both GVP soils, their accumulation extents in SG soil were both greater than that in RAPG soil. Cu and Zn were mainly originated from anthropogenic activities based on multivariate statistical analysis, which were greatly associated with excessive manure application. Overall, pXRF can identify the accumulation difference of PTEs between the two GVP soils, which is generally consistent with conventional laboratory analysis. Hence, pXRF can be a promising alternative to conventional laboratory analysis for rapid assessment of PTEs accumulation, sources, and the potential ecological risk in the two GVP soils. Although PTEs had a low ecological risk, Cu and Zn accumulation in SG soil was increased with the planting years. Therefore, rational application of livestock manure containing high levels of Cu and Zn should inspire strategies to mitigate the environmental risk in GVP soils, especially in SG soil.