ALKBH5 promotes lung fibroblast activation and silica-induced pulmonary fibrosis through miR-320a-3p and FOXM1.

BACKGROUND: N6-methyladenosine (m6A) is the most common and abundant internal modification of RNA. Its critical functions in multiple physiological and pathological processes have been reported. However, the role of m6A in silica-induced pulmonary fibrosis has not been fully elucidated. AlkB homolog 5 (ALKBH5), a well-known m6A demethylase, is upregulated in the silica-induced mouse pulmonary fibrosis model. Here, we sought to investigate the function of ALKBH5 in pulmonary fibrosis triggered by silica inhalation. METHODS: We performed studies with fibroblast cell lines and silica-induced mouse pulmonary fibrosis models. The expression of ALKBH5, miR-320a-3p, and forkhead box protein M1 (FOXM1) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RNA immunoprecipitation (RIP) assays and m6A RNA immunoprecipitation assays (MeRIP), western bolt, immunofluorescence assays, and 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining were performed to explore the roles of ALKBH5, miR-320a-3p, and FOXM1 in fibroblast activation. RESULTS: ALKBH5 expression was increased in silica-inhaled mouse lung tissues and transforming growth factor (TGF)-ß1-stimulated fibroblasts. Moreover, ALKBH5 knockdown exerted antifibrotic effects in vitro. Simultaneously, downregulation of ALKBH5 elevated miR-320a-3p but decreased pri-miR-320a-3p. Mechanically, ALKBH5 demethylated pri-miR-320a-3p, thus blocking the microprocessor protein DGCR8 from interacting with pri-miR-320a-3p and leading to mature process blockage of pri-miR-320a-3p. We further demonstrated that miR-320a-3p could regulate fibrosis by targeting FOXM1 messenger RNA (mRNA) 3'-untranslated region (UTR). Notably, our study also verified that ALKBH5 could also directly regulate FOXM1 in an m6A-dependent manner. CONCLUSIONS: Our findings suggest that ALKBH5 promotes silica-induced lung fibrosis via the miR-320a-3p/FOXM1 axis or targeting FOXM1 directly. Approaches aimed at ALKBH5 may be efficacious in treating lung fibrosis.

PTX3 alleviates hard metal-induced acute lung injury through potentiating efferocytosis.

Prolonged exposure to hard metal dust results in hard metal lung disease (HMLD) characterized by respiratory symptoms. Understanding the pathogenesis and pathological process of HMLD would be helpful for its early diagnosis and treatment. In this study, we established a mouse model of hard metal-induced acute lung injury through one-time intratracheal instillation of WC-Co dust suspension. We found that WC-Co treatment damaged the lungs of mice, leading to increased production of IL-1ß, TNF-α, IL-6 and IL-18, inflammatory cells infiltration and apoptosis. In vitro, WC-Co induced cytotoxicity, inflammatory response and apoptosis in macrophages (PMA-treated THP-1) and epithelial cells (A549) in a dose-dependent manner. Moreover, RNA-sequence and validation experiments verified that Pentraxin 3 (PTX3), an important mediator in the regulation of inflammation, was elevated both in vivo and in vitro induced by WC-Co. Functional experiments confirmed the PTX3, which was located on the membrane of apoptotic cells, promoted macrophage efferocytosis efficiently. This progress could help block the lung inflammation and contribute to the rapid recovery of WC-Co-induced acute lung injury. These observations provide a further understanding of the molecular mechanism of WC-Co-induced pulmonary injury and disclose PTX3 as a new potential therapeutic approach to relieve WC-Co-induced acute lung injury via efferocytosis.

LncRNA-ATB regulates epithelial-mesenchymal transition progression in pulmonary fibrosis via sponging miR-29b-2-5p and miR-34c-3p.

Dysregulation of non-coding RNAs (ncRNAs) has been proved to play pivotal roles in epithelial-mesenchymal transition (EMT) and fibrosis. We have previously demonstrated the crucial function of long non-coding RNA (lncRNA) ATB in silica-induced pulmonary fibrosis-related EMT progression. However, the underlying molecular mechanism has not been fully elucidated. Here, we verified miR-29b-2-5p and miR-34c-3p as two vital downstream targets of lncRNA-ATB. As opposed to lncRNA-ATB, a significant reduction of both miR-29b-2-5p and miR-34c-3p was observed in lung epithelial cells treated with TGF-ß1 and a murine silicosis model. Overexpression miR-29b-2-5p or miR-34c-3p inhibited EMT process and abrogated the pro-fibrotic effects of lncRNA-ATB in vitro. Further, the ectopic expression of miR-29b-2-5p and miR-34c-3p with chemotherapy attenuated silica-induced pulmonary fibrosis in vivo. Mechanistically, TGF-ß1-induced lncRNA-ATB accelerated EMT as a sponge of miR-29b-2-5p and miR-34c-3p and shared miRNA response elements with MEKK2 and NOTCH2, thus relieving these two molecules from miRNA-mediated translational repression. Interestingly, the co-transfection of miR-29b-2-5p and miR-34c-3p showed a synergistic suppression effect on EMT in vitro. Furthermore, the co-expression of these two miRNAs by using adeno-associated virus (AAV) better alleviated silica-induced fibrogenesis than single miRNA. Approaches aiming at lncRNA-ATB and its downstream effectors may represent new effective therapeutic strategies in pulmonary fibrosis.

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling.

BACKGROUND: Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. METHODS: The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-ß1)-induced differentiated lung fibroblasts were used for in vitro models. RESULTS: At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2-10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-ß1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. CONCLUSIONS: In this study, we identified that metformin might be a potential drug for silicosis treatment.

Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N6-methyladenosine of Notch1.

BACKGROUND: N6-methyladenosine (m6A) emerges as one of the most important modification of RNA. Bladder cancer is a common cancer type in developed countries, and hundreds of thousands of bladder cancer patients die every year. MATERIALS AND METHODS: There are various cells in bladder tumor bulk, and a small population cells defined as tumor initiating cells (TIC) have self-renewal and differentiation capacities. Bladder TICs drive bladder tumorigenesis and metastasis, and their activities are fine regulated. However, the role of N6-methyladenosine in bladder TIC self-renewal is unknown. RESULTS: Here, we found a decrease of N6-methyladenosine in bladder tumors and bladder TICs. N6-methyladenosine levels are related to clinical severity and outcome. Mettl14 is lowly expressed in bladder cancer and bladder TICs. Mettl14 knockout promotes the proliferation, self-renewal, metastasis and tumor initiating capacity of bladder TICs, and Mettl14 overexpression exerts an opposite role. Mettl14 and m6A modification participate in the RNA stability of Notch1 mRNA. Notch1 m6A modification inhibits its RNA stability. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal. CONCLUSION: This work reveals a novel role of Mettl14 and N6-methyladenosine in bladder tumorigenesis and bladder TICs, adding new layers for bladder TIC regulation and N6-methyladenosine function.

Introducing the Quill™ device for modified sleeve circumcision with subcutaneous suture: a retrospective study of 70 cases.

OBJECTIVE: The purpose of the study was to evaluate the safety and feasibility of treatment for male circumcision using modified sleeve circumcision and subcuticular suture with the Quill™ device. METHODS: From May 2011 to March 2012, 70 consecutive cases of male circumcision were performed using an alternative technique with the Quill™ device by a single surgeon in our institution. The inclusion and exclusion criteria for the selection process of this procedure were the same as for conventional circumcision. We evaluated the indications and perioperative outcomes. The circumcisions were performed as day-case procedures under local anesthesia. RESULTS: All patients were followed up for a minimum of 3-6 months. The ages ranged from 8 to 68 (mean = 27.0 years, SD = 10). The indications for surgery were either cosmetic (n = 16, 22.9%) or medical [redundant prepuce (n = 36, 51.4%), phimosis (n = 5, 7.1%), paraphimosis (n = 2, 2.9%), balanoposthitis (n = 9, 12.9%), melanoma (n = 1, 1.4%), and condyloma acuminata (n = 1, 1.4%)] (n = 54, 77.1%). The mean operation time in this group was 29 min (19-38 min) when the Quill™ device was used. In all, 3 cases developed complications (4.3%). The final cosmetic result was satisfactory for both the patients and their spouses or parents. CONCLUSION: This study showed that modified sleeve circumcision and subcuticular suture were safe and reliable surgical methods of circumcision that provide a better cosmetic result.

circPVT1 promotes silica-induced epithelial-mesenchymal transition by modulating the miR-497-5p/TCF3 axis.

Epithelial-mesenchymal transition (EMT) is a vital pathological feature of silica-induced pulmonary fibrosis. However, whether circRNA is involved in the process remains unclear. The present study aimed to investigate the role of circPVT1 in the silica-induced EMT and the underlying mechanisms. We found that an elevated expression of circPVT1 promoted EMT and enhanced the migratory capacity of silica-treated epithelial cells. The isolation of cytoplasmic and nuclear separation assay showed that circPVT1 was predominantly expressed in the cytoplasm. RNA immunoprecipitation assay and RNA pull-down experiment indicated that cytoplasmic-localized circPVT1 was capable of binding to miR-497-5p. Furthermore, we found that miR-497-5p attenuated the silica-induced EMT process by targeting transcription factor 3 (TCF3), an E-cadherin transcriptional repressor, in the silica-treated epithelial cells. Collectively, these results reveal a novel role of the circPVT1/miR-497-5p/TCF3 axis in the silica-induced EMT process in lung epithelial cells. Once validated, this finding may provide a potential theoretical basis for the development of interventions and treatments for pulmonary fibrosis.

Effects of combined physical and cognitive training on executive function of adolescent shooting athletes: A functional near-infrared spectroscopy study.

Individual executive function improvement through physical and cognitive training is a research hotspot in physical education and cognitive science. However, few studies have evaluated whether combined physical and cognitive training (CPCT) has greater benefits for executive function performance and cerebral oxygenation in adolescent athletes than cognitive training alone. This study randomly assigned 33 adolescent shooting athletes to a CPCT (n â€‹= â€‹17) or computerized cognitive training (CCT, n â€‹= â€‹16) group and compared their executive function after six weeks of training. All subjects were assessed using the 2-back, task-switching, and Stroop tests before and after training. The prefrontal cortex oxygenated hemoglobin (Oxy-Hb) activation level was monitored while executing the three tasks using functional near-infrared spectroscopy. Our results showed that the CPCT and CCT groups similarly improved their updating function as indicated by the 2-back task accuracy. The CPCT group significantly improved the switching function in the task-switching test accuracy, while the CCT group did not. However, both groups did not improve in behavioral performance as indicated by the inhibition function in the Stroop task. Cerebral oxygenation, indicated by the oxy-Hb activation level in the frontal pole area of the prefrontal lobe, significantly improved in the CPCT group during the three cognitive tasks, whereas the CCT group showed no change. These findings indicated that CPCT endowed greater advantages in task-switching in the behavioral performance of the executive function than CCT. Moreover, CPCT was superior to CCT in increasing task-efficient cerebral oxygenation during the activation of the prefrontal cortex in adolescent shooting athletes.

Family functioning and mobile phone addiction in university students: Mediating effect of loneliness and moderating effect of capacity to be alone.

Background: With the increasing popularity of smartphones, mobile phone addiction in university students has attracted widespread societal attention. Previous studies showed that family functioning and mobile phone addiction are related. However, the potential mechanisms involved in this relationship are unknown. This study examined the mediating effect of loneliness and the moderating effect of capacity to be alone on the relationship between family functioning and mobile phone addiction. Methods: A total of 1,580 university students were recruited. A cross-sectional study design and online questionnaire survey were employed to measure demographic variables, family functioning, loneliness, capacity to be alone, and mobile phone addiction in university students. Results: Family functioning is a significantly negative predictor of mobile phone addiction in university students, and loneliness has a mediating effect on the relationship between family functioning and mobile phone addiction. The capacity to be alone has moderating effects on the relationship between family functioning and loneliness and between family functioning and mobile phone addiction, and these correlation is stronger in university students with a low capacity to be alone. Conclusion: The moderated mediation model in this study improves understanding of the correlation between family functioning and mobile phone addiction in university students. Education professionals and parents should pay particular attention to family functioning in mobile phone addiction, particularly university students with low capacity to be alone.

Xiaopiyishen Herbal Extract Granule Improves the Quality of Life among People with Fatigue-Predominant Subhealth and Liver-Qi Stagnation and Spleen-Qi Deficiency Syndrome.

To observe the effects of Xiaopiyishen Herbal Extract Granule (XPYS-HEG) on the quality of life in people with fatigue-predominant subhealth (FPSH) and liver-qi stagnation and spleen-qi deficiency syndrome, the participants were allocated randomly to the treatment group (XPYS, n = 100) and the control group (placebo, n = 100) in this study. The study period was 18 weeks (6 weeks for the intervention and 12 weeks for followup). The results show that there were no differences between the two groups for the scores of eight factors on the SF-36 (Chinese version of the SF-36 universal quality-of-life scale) at baseline. Compared with the baseline score, intervention with XPYS-HEG led to a significant increase in scores for the factor of bodily pain at the end of the 6th week. Compared with the score at the end of the 6th week, the score for the factor of mental health in the XPYS group significantly increased at the end of the 18th week. Therefore, XPYS-HEG could partially improve the quality of life for people with FPSH and liver-qi stagnation and spleen-qi deficiency syndrome, which can ease bodily pain, stimulate a positive mood, and ease a negative mood.

Feed-forward offset-free model predictive temperature control for proton exchange membrane fuel cell: An experimental study.

Safe and economic operation of an open-cathode proton exchange membrane fuel cell (PEMFC) requires an efficient thermal management strategy. The stack temperature regulation in PEMFC is, however, challenging due to often stringent set-point tracking tasks, frequent load fluctuations, constrained manipulated variables, and various modeling uncertainties and nonlinearities. To this end, a feed-forward offset-free model predictive control (MPC) approach, aiming at uncertainties resolving and disturbance mitigation, is developed to simultaneously address the above difficulties. In the proposed framework, the information about the measured power load fluctuations is used in the optimization algorithm as feed-forward information to eventually mitigate the influence of load fluctuations on the controlled output and increases the overall control quality. Additionally, the unmodeled dynamics and the other unmeasurable disturbances/uncertainties are collectively considered as an extended state of the system (to achieve zero static errors) and the on-line reconstructed aggregated disturbances is continuously sent to the MPC algorithm to increase its optimization performance and to achieve offset-free control objectives. The obtained results are quantitatively compared with conventional control strategies for PEMFCs, including a model-based PI controller, its modification utilizing disturbance feed-forward, and a standard offset-free MPC (i.e. without feed-forward). Both the simulations, realized in MATLAB/Simulink, and hardware experiments, conducted on a 500 W PEMFC testbed, show excellence of the proposed feed-forward offset-free MPC consisting in faster temperature tracking and higher robustness. The obtained satisfactory results show the introduced control solution to be a promising prospect and help accelerating further applications of PEMFCs.

Liangxue Jiedu Runzhi ointment in the treatment of mild and moderate psoriasis with blood-heat syndrome: A double-blind randomized controlled trial.

INTRODUCTION: Psoriasis is a kind of chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales and keratinocyte hyperproliferation. Psoriasis Vulgaris, the most common kind of psoriasis, severely deteriorates the life quality of patients. Traditional Chinese Medicine (TCM) is a good choice for the treatment of psoriasis, which has been proved to be safe and effective, and may reduce the recurrence rate. In clinical practice, Liangxue Jiedu Runzhi (LJR) ointment can effectively treat mild and moderate psoriasis with blood-heat syndrome, but there is a lack of evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of LJR ointment for the treatment of mild and moderate psoriasis with blood-heat syndrome. METHODS: A multicenter, randomized, double-blind, placebo-controlled, and self-controlled clinical trial was carried out according to this paper. The symmetrical rashes of each subject were regarded as the target lesions and were randomly divided into a treatment group (LJR ointment group) and a control group (placebo group). The LJR ointment or placebo ointment were externally administered on bilateral symmetric rashes, twice a day for eight weeks. The follow-up examination was made for subjects every two weeks. The primary research finding was conveyed by Psoriasis Area and Severity Index (PASI) in 8 weeks. The secondary research finding includes adverse events. RESULTS: 46 subjects undergo this research project. The difference between PASI scores of the target lesions in the treatment group and control group is statistically significant were in 8 weeks (P < .001). The percentage of PASI 75 in treatment group and control group were 48% and 15% in week 8, respectively (x2 = 11.33, P < .05). No severe adverse events were reported. CONCLUSIONS: LJR ointment was proved to have efficacy in the treatment of mild and moderate psoriasis with the blood-heat syndrome.

Caveolin-1 and Its Functional Peptide CSP7 Affect Silica-Induced Pulmonary Fibrosis by Regulating Fibroblast Glutaminolysis.

Exposure to silica is a cause of pulmonary fibrosis disease termed silicosis, which leads to respiratory failure and ultimately death. However, what drives fibrosis is not fully elucidated and therapeutic options remain limited. Our previous RNA-sequencing analysis showed that the expression of caveolin-1 (CAV1) was downregulated in silica-inhaled mouse lung tissues. Here, we not only verified that CAV1 was decreased in silica-induced fibrotic mouse lung tissues in both messenger RNA and protein levels, but also found that CSP7, a functional peptide of CAV1, could attenuate pulmonary fibrosis in vivo. Further in vitro experiments revealed that CAV1 reduced the expression of Yes-associated protein 1(YAP1) and affected its nuclear translocation in fibroblasts. In addition, Glutaminase 1 (GLS1), a key regulator of glutaminolysis, was identified to be a downstream effector of YAP1. CAV1 could suppress the activity of YAP1 to decrease the transcription of GLS1, thereby inhibiting fibroblast activation. Taken together, our results demonstrated that CAV1 and its functional peptide CSP7 may be potential molecules or drugs for the prevention and intervention of silicosis.

UHRF1-mediated ferroptosis promotes pulmonary fibrosis via epigenetic repression of GPX4 and FSP1 genes.

Pulmonary fibrosis (PF), as an end-stage clinical phenotype of interstitial lung diseases (ILDs), is frequently initiated after alveolar injury, in which ferroptosis has been identified as a critical event aggravating the pathophysiological progression of this disease. Here in, a comprehensive analysis of two mouse models of pulmonary fibrosis developed in our lab demonstrated that lung damage-induced ferroptosis of alveolar epithelial Type2 cells (AEC2) significantly accumulates during the development of pulmonary fibrosis while ferroptosis suppressor genes GPX4 and FSP1 are dramatically inactivated. Mechanistically, upregulation of de novo methylation regulator Uhrf1 sensitively elevates CpG site methylation levels in promoters of both GPX4 and FSP1 genes and induces the epigenetic repression of both genes, subsequently leading to ferroptosis in chemically interfered AEC2 cells. Meanwhile, specific inhibition of UHRF1 highly arrests the ferroptosis formation and blocks the progression of pulmonary fibrosis in both of our research models. This study first, to our knowledge, identified the involvement of Uhrf1 in mediating the ferroptosis of chemically injured AEC2s via de novo promoter-specific methylation of both GPX4 and FSP1 genes, which consequently accelerates the process of pulmonary fibrosis. The above findings also strongly suggested Uhrf1 as a novel potential target in the treatment of pulmonary fibrosis.

[Effects of Xiaopi Yishen herbal extract granules in treatment of fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency: a prospective, randomized, placebo-controlled and double-blind clinical trial].

BACKGROUND: The demand for effective intervention for subhealth conditions is growing with increasing numbers of people being in a state of subhealth with a poor quality of life. Future research and evaluation of the treatment methods for subhealth conditions from the perspective of traditional Chinese medicine (TCM) may provide an important direction for developing effective management of these conditions. OBJECTIVE: To evaluate the efficacy and safety of Xiaopi Yishen herbal extract granules (XPYS-HEG), a compound traditional Chinese herbal medicine for relieving fatigue and promoting a cheerful spirit for the treatment of people with fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency. DESIGN, SETTING PARTICIPANTS AND INTERVENTIONS: A multi-center, randomized, double-blinded, placebo-controlled clinical study was undertaken. The study period was 18 weeks, including 6 weeks for intervention and 12 weeks for follow-up. Participants were recruited from medical center and outpatient clinics of three hospitals in China, i.e. Xiaotangshan Hospital of Beijing, the First Affiliated Hospital of Henan University of TCM and the Affiliated Hospital of Liaoning University of TCM. Two hundred participants who met the criteria of fatigue-predominant subhealth and liver-qi stagnation and spleen-qi deficiency in TCM were allocated randomly to the treatment group (XPYS, n=100) and control group (placebo, n=100). MAIN OUTCOME MEASURES: The total score of Fatigue Scale-14 (FS-14) was used to evaluate the fatigue status of subjects and the extent of liver-qi stagnation and spleen-qi deficiency syndrome was also recorded. RESULTS: Three cases in the XPYS group withdrew from the trial. There were 200 subjects who entered to full analysis set (FAS) analysis and 197 subjects fitted in the per-protocol set (PPS) analysis. (1) According to the score changes of FS-14, the effectiveness rates in the XPYS and placebo group were as follows: 14.0% vs 9.0% (FAS) and 14.4% vs 9.0% (PPS) for complete remission, 19.0% vs 15.0% (FAS) and 19.6% vs 15.0% (PPS) for obvious effects, 39.0% vs 26.0% (FAS) and 39.2% vs 26.0% (PPS) for effective, and 72.0% vs 50.0% (FAS) and 73.2% vs 50.0% (PPS) for complete efficacy. The efficacy of XPYS-HEG was superior to the placebo statistically (P<0.05). (2) According to the score changes of TCM syndrome, the effectiveness rates in the XPYS group and placebo group were as follows: 1.0% vs 0.0% (FAS) and 1.0% vs 0.0% (PPS) for complete remission, 20.0% vs 7.0% (FAS) and 19.6% vs 7.0% (PPS) for obvious effects, 29.0% vs 24.0% (FAS) and 29.9% vs 24.0% (PPS) for effective, and 50.0% vs 31.0% (FAS) and 50.5% vs 31.0% (PPS) for complete efficacy. The efficacy of XPYS-HEG was superior to that of placebo statistically (P<0.05). (3) The follow-up results at 12 weeks and 18 weeks showed that the efficacy of XPYS-HEG was superior to that of placebo statistically (P<0.05). (4) No adverse effects were found in the XPYS group. CONCLUSION: It can be concluded that XPYS-HEG is effective and safe for the treatment of people with fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency.

Long noncoding RNA-SNHG20 promotes silica-induced pulmonary fibrosis by miR-490-3p/TGFBR1 axis.

Silicosis is a universal occupational disease, which is caused by long-term crystalline silica exposure. Recent studies have shown that noncoding RNAs participate in diverse pathological cellular pathways. However, the precise regulation mechanism remains limited in silicosis. Here, we established a silica-induced mouse fibrosis model (all mice received a one-time intratracheal instillation with 50 mg/kg of silica in 0.05 mL sterile saline). MiR-490-3p was significantly downregulated in silica-induced fibrotic mouse lung tissues and TGF-ß1 treated fibroblasts. Moreover, overexpressed miR-490-3p could relieve silica-induced lung fibrosis in vivo, and prevent the process of fibroblast-to-myofibroblast transition(FMT)in vitro. Mechanistically, TGFBR1 was one of the major target genes of miR-490-3p, and tightly associated with the process of fibroblasts activation. SNHG20, as opposed to miR-490-3p expression, was elevated in TGF-ß1-treated fibroblast cell lines and contributed to decreased levels of miR-490-3p. Taken together, these data indicated that miR-490-3p plays a key role in silica-induced pulmonary fibrosis. Our results suggested that SNHG20/miR-490-3p/TGFBR1 axis may provide a new treatment target of pulmonary fibrosis.

CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner.

Pulmonary fibrosis develops when myofibroblasts and extracellular matrix excessively accumulate in the injured lung, but what drives fibrosis is not fully understood. Glycolysis has been linked to cell growth and proliferation, and several studies have shown enhanced glycolysis promotes pulmonary fibrosis. However, detailed studies describing this switch remain limited. Here, we identified that TGF-ß1 effectively increased the expression of circHIPK3 in lung fibroblasts, and circHIPK3 inhibition attenuated the activation, proliferation, and glycolysis of fibroblasts in vitro. Dual-luciferase reporter gene assays, RNA immunoprecipitation (RIP), and RNA pull-down assays showed that circHIPK3 could function as a sponge of miR-30a-3p and inhibit its expression. Furthermore, FOXK2, a driver transcription factor of glycolysis, was identified to be a direct target of miR-30a-3p. Mechanistically, circHIPK3 could enhance the expression of FOXK2 via sponging miR-30a-3p, thereby facilitating fibroblast glycolysis and activation. Besides, miR-30a-3p overexpression or FOXK2 knockdown blocked fibroblast activation induced by TGF-ß1 and abrogated the profibrotic effects of circHIPK3. Moreover, circHIPK3 and miR-30a-3p were also dysregulated in fibrotic murine lung tissues induced by silica. Adeno-associated virus (AAV)-mediated circHIPK3 silence or miR-30a-3p overexpression alleviated silica-induced pulmonary fibrosis in vivo. In conclusion, our results identified circHIPK3/miR-30a-3p/FOXK2 regulatory pathway as an important glycolysis cascade in pulmonary fibrosis.

Efficacy of nano-modified Runji ointment in the treatment of mild and moderate psoriasis with blood dryness syndrome: a study protocol for a double-blind randomized controlled trial.

INTRODUCTION: Psoriasis is a common, recurrent, immune skin disease, which seriously affects patients' quality of life. In clinical practice, modified Runji ointment can effectively treat mild-to-moderate psoriasis with blood dryness syndrome, but there is a lack of high-quality evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of nano-modified Runji ointment in the treatment of mild-to-moderate psoriasis with blood dryness syndrome. METHODS/DESIGN: This study will be a randomized double-blind placebo-controlled trial. A total of 80 patients will be recruited and randomly divided into an intervention group (nano-modified Runji ointment group) and a placebo group at a ratio of 1:1. All included patients will receive 8 weeks of nano-modified Runji ointment or placebo ointment respectively, twice a day. The primary outcome will be the change in psoriasis area and disease severity index score at week 8 compared to baseline. The secondary outcomes will be rash area score, pruritus score, Dermatology Life Quality Index score, traditional Chinese medicine symptom score and adverse events. DISCUSSION: This study may provide high-quality evidence for the efficacy of nano-modified Runji ointment in the treatment of mild to moderate psoriasis with blood dryness syndrome. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION: ChiCTR, ChiCTR2000034292. Registered July 1, 2020, https://www.chictr.org.cn/edit.aspx?pid=55884&htm=4.

[Distribution characteristics of traditional Chinese medicine syndromes and their elements in people with subhealth fatigue].

OBJECTIVE: To investigate the characteristics of traditional Chinese medicine (TCM) syndromes and their elements in people with subhealth fatigue. METHODS: The TCM symptoms in line with the diagnostic criteria of subhealth fatigue status were collected by clinical investigations and using information collection form based on TCM four diagnostic methods. Referred to Clinical Guidelines of Chinese Medicine on Subhealth and other related standards, the syndrome type was identified in accordance with clinical symptoms of each patient with subhealth fatigue by two physicians. The data of syndrome differentiation were analyzed by descriptive statistical analysis. RESULTS: There were 81 syndrome types from 495 cases of subhealth fatigue. There were 24 syndrome types after separation, and the top ten were liver stagnation and spleen deficiency, stagnation of liver qi, hyperactivity of liver fire, disharmony between liver and stomach, damp obstruction due to spleen deficiency, deficiency of both heart and spleen, yin deficiency of liver and kidney, yang deficiency of spleen and kidney, stagnation of gallbladder and disturbance of phlegm, and internal disturbance of phlegm-heat. There were 17 syndrome elements, including seven disease location elements and ten disease nature elements. The disease location elements were liver, spleen, kidney, stomach, heart, gallbladder and lung. The disease nature elements were qi stagnation, qi deficiency, exuberance of fire (heat), damp obstruction, phlegm obstruction, yin deficiency, adverse flow of qi, yang deficiency, blood deficiency, and blood stasis. CONCLUSION: Syndrome types of subhealth fatigue involve in deficiency syndrome, excess syndrome, and mixture of deficiency and excess syndromes. The syndrome elements of disease location involve five zang organs and two fu organs, and the liver and spleen were the most frequently involved organs. The syndrome elements of disease nature involve deficiency and excess. Qi stagnation is most frequently involved in the excess syndrome, and qi deficiency is most frequently involved in the deficiency syndrome.