1,25-hydroxyvitamin D relieves colitis in rats via downregulation of toll-like receptor 9 expression

Aim To investigate the therapeutic and immunoregulatory effects of 1,25-dihydroxyvitamin D (1,25(OH)D3) on 2,4,6- trinitrobenzenesulfonic acid (TNBS) -induced colitis in rats. Methods Experimental colitis induced by enema administration of TNBS plus ethanol was treated with 5-aminosalicylic acid (5-ASA) and/or 1,25(OH)D3. Disease activity was measured using the disease activation index (DAI), colon macroscopic damage index (CMDI), histological colonic damage score, and myeloperoxidase (MPO) activity. The expression of toll-like receptor 9 (TLR9) in the colon was determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Results Rats with TNBS-induced colitis had significantly elevated DAI, CMDI, histological colonic damage score, and MPO activity (all P < 0.001) compared to rats without colitis. Treatment with 5-ASA or 1,25(OH)D3 ameliorated colitis by lowering CMDI (P = 0.049, P = 0.040, respectively), histological colonic damage score (P = 0.010, P = 0.005, respectively), and MPO activity (P = 0.0003, P = 0.0013, respectively) compared with the TNBS group. Combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased MPO activity (P = 0.003). 1,25(OH)D3 attenuated colitis without causing hypercalcemia or renal insufficiency. TNBS significantly increased the number of TLR9 positive cells compared to control (P < 0.010), while 5-ASA, 1,25(OH)D3, and combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased it compared to TNBS group (all P < 0.010). In TNBS group a moderate correlation was observed between MPO activity and the number of TLR9-positive cells (r = 0.654, P < 0.001). Conclusion TLR9 expression correlates with the extent of inflammation in TNBS-induced colitis. 1,25(OH)D3 relieves this inflammation possibly by decreasing TLR9 expression

Terazosin Analogs Targeting Pgk1 as Neuroprotective Agents: Design, Synthesis, and Evaluation

Nitrogen-containing heterocyclic compounds have shown promising therapeutic effects in a variety of inflammatory and neurodegenerative diseases. Recently, terazosin (TZ), a heterocyclic compound with a quinazoline core, was found to combine with phosphoglycerol kinase 1 (Pgk1) and protect neurons by enhancing Pgk1 activity and promoting glycolysis, thereby slowing, or preventing the neurodegeneration of PD. These findings indicated that terazosin analogs have bright prospects for the development of PD therapeutics. In this study, a series of terazosin analogs were designed and synthesized for neuroprotective effects by targeting Pgk1. Among them, compound 12b was obtained with the best Pgk1 agonistic activity and neuroprotective activity. Further study indicates that it can increase intracellular ATP content and reduce ROS levels by stimulating the activity of Pgk1, thereby playing a role in protecting nerve cells. In conclusion, this study provides a new strategy and reference for the development of neuroprotective drugs

Auto-diagnosis of time-of-flight for ultrasonic signal based on defect peaks tracking model

With the popularization of humans working in tandem with robots and artificial intelligence (AI) by Industry 5.0, ultrasonic non-destructive testing (NDT)) technology has been increasingly used in quality inspections in the industry. As a crucial part of handling ultrasonic testing results–signal processing, the current approach focuses on professional training to perform signal discrimination but automatic and intelligent signal optimization and estimation lack systematic research. Though the automated and intelligent framework for ultrasonic echo signal processing has already exhibited essential research significance for diagnosing defect locations, the real-time applicability of the algorithm for the time-of-flight (ToF) estimation is rarely considered, which is a very important indicator for intelligent detection. This paper conducts a systematic comparison among different ToF algorithms for the first time and presents the auto-diagnosis of the ToF approach based on the Defect Peaks Tracking Model (DPTM). The proposed DPTM is used for ultrasonic echo signal processing and recognition for the first time. The DPTM using the Hilbert transform was verified to locate the defect with the size of 2–10 mm, in which the wavelet denoising method was adopted. With the designed mechanical fixture through 3D printing technology on the pipeline to inspect defects, the difficulty of collecting sufficient data could be conquered. The maximum auto-diagnosis error could be reduced to 0.25% and 1.25% for steel plate and pipeline under constant pressure, respectively, which were much smaller than those with the DPTM adopting the cross-correlation. The real-time auto-diagnosis identification feature of DPTM has the potential to be combined with AI in future work, such as machine learning and deep learning, to achieve more intelligent approaches for industrial health inspection

Biological N fixation but not mineral N fertilization enhances the accumulation of N in peanut soil in maize/peanut intercropping system

Legume/cereal intercropping has the potential to maximize the use of resources to raise yields due to enhanced nitrogen (N) fixation by legume root nodules, while high N fertilization may inhibit the nodulation of legume. However, whether legume/cereal intercropping can promote the accumulation of soil N storage with N fertilization and its underlying mechanism are less clear. Here, we evaluated the long-term (5 years) effects of maize/peanut intercropping and mineral N fertilization on peanut soil total N content and soil N cycling functional genes. The experiment includes two planting patterns (peanut maize intercropping and peanut monocropping) with three N fertilization rates (0, 150, and 300 kg N ha−1). Intercropping increased soil total N content (STN) by average 18.2%, and the positive effect of intercropping on STN decreased with N application rate. Highest N application decreased the nodule fresh weight (NFW) by 64.3% and 46.0% in intercropping and monocropping system, respectively. However, intercropping has no effect on NFW. Intercropping increased the nifH gene abundance by average 26.5%. SEM analysis indicated that NFW and nifH gene abundance combined can explain 46% of the variance of STN. Our results indicate that biological N fixation but not mineral N fertilization enhances the accumulation of N in soil planted with peanut in maize/peanut intercropping system.info:eu-repo/semantics/publishedVersio

Incidence of suboptimal response to tumor necrosis factor antagonist therapy in inflammatory bowel disease in newly industrialised countries: The EXPLORE study

Abstract Background Incidence of inflammatory bowel disease (IBD) is increasing in newly industrialised countries (NICs); however, data on suboptimal response to anti-tumor necrosis factor (anti-TNF) agents are limited. Objectives To assess incidence and indicators of suboptimal response to first anti-TNF therapy in IBD patients in NICs. Methods A chart review was conducted in ten countries from Asia-Pacific (APAC), Latin America (LatAm), and Russia and the Middle East (RME) regions among patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD), initiating anti-TNF therapy in 2010–2015. The cumulative incidence of suboptimal response to anti-TNF therapy was assessed using the following indicators: dose escalation or discontinuation, augmentation with non-biologic therapy, IBD-related hospitalization, or surgery. Results The study included 1,674 patients (570 UC; 1,104 CD). At 24 months, 32.9% of UC (APAC: 45.1%; LatAm: 38.2%; RME: 23.8%) and 41.2% of CD patients (APAC: 54.1%; LatAm: 42.5%; RME: 29.5%) had experienced suboptimal response. The most frequent first indicator was non-biologic therapy augmentation in LatAm (41.7%), IBD-related hospitalization in RME (UC: 50.7%; CD:37.3%) and in APAC for CD (39.1%), and anti-TNF discontinuation in APAC for UC (38.3%). Conclusion Suboptimal response to anti-TNF agents is common in IBD patients in NICs. Observed regional differences in the incidence and indicators may reflect local practice and anti-TNF restrictions in IBD management. NCT Registration Number NCT03090139

Resveratrol regulates insulin resistance to improve the glycolytic pathway by activating SIRT2 in PCOS granulosa cells

ScopeInsulin resistance (IR) has a close relationship with the main clinical manifestations of patients with PCOS; hence, the research and development of new drugs to treat PCOS by improving IR is a desiderate task at present. Resveratrol (RES) possesses a variety of beneficial pharmacological functions, such as antioxidation, anti-inflammatory, regulating glucose, and lipid metabolism. However, whether RES could improve IR and the underlying mechanisms remained unclear in PCOS.Methods and resultsSD rats received a high-fat diet and letrozole for 30 days to establish the PCOS model and then intervened with RES for 30 days. The results demonstrated that RES played a protective role on the IR in PCOS rats, which significantly decreased the levels of blood glucose and serum insulin, up regulated the expression of IGF1R, and down regulated the expression of IGF1. In vitro, KGN cells were treated with insulin, RES, and AGK2, respectively. We found that a high dose of insulin (4μg/mL) significantly inhibited KGN cell viability, decreased the level of lactic acid, and increased the level of pyruvate, while RES (25μM) attenuated the growth-inhibitory effect, as well as increased the level of lactic acid and decreased the level of pyruvate after high levels of insulin treatment. Simultaneously, RES up regulated the expression level of the crucial rate-limiting enzymes relating to glycolytic pathways, such as LDHA, HK2, and PKM2. Furthermore, AGK2 remarkably inhibited the expression level of SIRT2, which was similar to the same negative effects processed by insulin. Meanwhile, RES overtly repaired the glycolysis process by reversing the levels of lactic acid and pyruvate, together with up regulating the expression level of LDHA, HK2, and PKM2, after AGK2 treatment.ConclusionRES could effectively improve insulin resistance and restore the glycolysis pathway by regulating SIRT2, which may contribute to attenuating the ovarian damage of PCOS rats and provide a potential treatment for patients with PCOS