Clopidogrel (INN), an oral antiplatelet drug, has been revealed to have a number of biological properties, for instance, anti-inflammation and antioxidation. Oxidative stress plays an imperative role in inflammation, diabetes mellitus, atherosclerosis, and cancer. In the present study, human aortic endothelial cells (HAECs) were employed to explore the anti-inflammatory activity of INN. INN reduced TNFα-induced reactive oxygen species (ROS) generation and time-dependently prompted the expression and activity of heme oxygenase 1 (HO-1). Cellular glutathione (GSH) levels were augmented by INN. shHO-1 blocked the INN suppression of TNFα-induced HL-60 cell adhesion. The CaMKKβ/AMPK pathway and Nrf2 transcriptional factor were implicated in the induction of HO-1 by INN. Additionally, TNFαdramatically augmented VCAM-1 expression at protein and mRNA levels. INN treatment strikingly repressed TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Compound C, an AMPK inhibitor, and shNrf2 abolished TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Our data suggest that INN diminishes TNFα-stimulated VCAM-1 expression at least in part via HO-1 induction, which is CaMKKβ/AMPK pathway-dependent.

Background: Over the past decade, many studies in the field of transcranial direct current stimulation (tDCS) in stroke have been published in scholarly journals. However, a scientometric analysis focusing on tDCS after stroke is still missing. The purpose of this study is to deliver a bibliometric analysis to investigate the global hotspots and frontiers in the domain of tDCS in stroke from 2012 to 2021. Methods: Articles and reviews related to tDCS in stroke were retrieved and obtained from the Web of Science core collection database from 2012 to 2021. Data visualization and analysis were conducted by using CiteSpace, VOSviewer, and Microsoft Excel 2019. Results: Finally, 371 publications were included in the scientometric analysis, including 288 articles and 83 reviews. The results showed that the number of publications per year increased from 15 to 68 in the last 10 years. Neurosciences was the main research hotspot category (n = 201). Frontiers in Human Neuroscience was the most published journal with 14 papers. The most productive author, institution, and country were Fregni F (n = 13), the League of European Research Universities (n = 37), and the United States of America (n = 98), respectively. A burstness analysis of keywords and the literature indicated that current studies in the field of tDCS in stroke focused on poststroke aphasia, tDCS combined with robotic therapy, and anatomical parameters. Conclusion: The research of tDCS in stroke is predicted to remain a research hotspot in the future. We recommend investigating the curative effect of other different tDCS closed-loop rehabilitation methods for different stroke dysfunctions. In conclusion, this bibliometric study presented the hotspots and trends of tDCS in stroke over the last decade, which may help researchers manage their further studies.

Transcranial magnetic stimulation, as a relatively new type of treatment, is a safe and non-invasive method for pain therapy. Here, we used CiteSpace software to visually analyze 440 studies concerning transcranial magnetic stimulation in pain research from 2010 to 2021, indexed by Web of Science, to clarify the research hotspots in different periods and characterize the process of discovery in this field. The United States ranked first in this field. Lefaucheur JP, Fregni F, and Andrade ACD made great contributions to this field of study. The most prolific institution was University of São Paulo. The four main hot keywords were neuropathic pain, motor cortex, connectivity, and non-invasive brain stimulation. There were three main points that were generally accepted: (1) definite analgesic effect of high-frequency rTMS of M1 contralateral to pain side in neuropathic pain; (2) there are inconclusive recommendations regarding rTMS of the dorsolateral prefrontal cortex (DLPFC) in fibromyalgia and neuropathic pain; (3) there is low-quality evidence that single doses of high-frequency rTMS of the motor cortex may have short-term effects on chronic pain. This bibliometric analysis indicated that prospective, multi-center, large-sample, randomized controlled trials are still needed to further verify the effectiveness of various transcranial magnetic stimulation parameters in pain research.

Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to evaluate the efficacy of diaporine alone and in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin for the treatment of liver cancer. We demonstrated that diaporine, oxaliplatin, and doxorubicin triggered a concentration- and time-dependent decrease in the number of HepG2 cells. Diaporine at a concentration of 2.5 μM showed almost 100% inhibition of cell counts at 72 h. Similar effects were observed only with much higher concentrations (100 μM) of oxaliplatin or doxorubicin. Decreases in cell numbers after 48 h treatment with diaporine, oxaliplatin, and doxorubicin were also demonstrated in two additional hepatoma cell lines, Hep3B and Huh7. The combination of these drugs at low concentration for 48 h in vitro noticeably showed that diaporine improved the inhibitory effect on the number of cancer cells induced by oxaliplatin or doxorubicin. Additionally, this combination effectively inhibited colony growth in vitro. We found that inhibition of phosphorylation of ERK1/2 significantly increased when diaporine was used in combination with other agents. In addition, we also found that when diaporine was used in combination with doxorubicin or oxaliplatin, their proapoptotic effect greatly increased. We further revealed that the induction of apoptosis in hepatoma cells after treatment is due, at least in part, to the inhibition of phosphorylation of AKT, leading to the activation of caspase-3, inactivation of poly (ADP-ribose) polymerase (PARP), and subsequently to DNA damage, as indicated by the increased level of H2AX. Based on these findings, we suggest that diaporine in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin may play a role in the treatment of liver cancer.

This Purpose: This study investigates the energy metabolism characteristics of sprinters during speed endurance training with different rest intervals (1-min vs. 2-min). Twelve male sprinters (mean age: 19.85 ± 1.93 years, height: 182.75 ± 5.21 cm, weight: 66.08 ± 2.60 kg, training duration: 5.50 ± 1.12 years, personal best 200 m time: 22.88 ± 0.53 s) participated in the study. They underwent speed endurance training with 1-min and 2-min rest intervals. Blood lactate levels, oxygen consumption, and energy metabolism characteristics were recorded. Energy metabolism was assessed using a rapid calculation method based on “V”O₂, blood lactate (BLA), and excess post-exercise oxygen consumption (EPOC). Phosphagen energy supply during speed endurance training with 1-min rest intervals was 109.03 ± 12.34 kJ, while with 2-min rest intervals it was 82.33 ± 18.04 kJ. Glycolytic energy supply for the two modes was 189.79 ± 43.48 kJ and 167.45 ± 47.14 kJ, respectively. Aerobic metabolism energy supply was measured at 162.02 ± 10.71 kJ and 162.82 ± 13.33 kJ for the 1-min and 2-min rest intervals, respectively. Shorter rest intervals induce quicker physiological responses during interval training at a fixed intensity. Specifically, the 1-min rest interval is more effective in enhancing the phosphagen system. Male sprinters are advised to incorporate 1-min rest interval speed endurance training into their routines to improve cardiovascular function and anaerobic metabolism capacity, thereby enhancing overall speed endurance levels.