Exploring Pharmacological Mechanisms of Xuefu Zhuyu Decoction in the Treatment of Traumatic Brain Injury via a Network Pharmacology Approach

Objectives. Xuefu Zhuyu decoction (XFZYD), a traditional Chinese medicine (TCM) formula, has been demonstrated to be effective for the treatment of traumatic brain injury (TBI). However, the underlying pharmacological mechanisms remain unclear. This study aims to explore the potential action mechanisms of XFZYD in the treatment of TBI and to elucidate the combination principle of this herbal formula. Methods. A network pharmacology approach including ADME (absorption, distribution, metabolism, and excretion) evaluation, target prediction, known therapeutic targets collection, network construction, and molecule docking was used in this study. Results. A total of 119 bioactive ingredients from XFZYD were predicted to act on 47 TBI associated specific proteins which intervened in several crucial pathological processes including apoptosis, inflammation, antioxidant, and axon genesis. Almost each of the bioactive ingredients targeted more than one protein. The molecular docking simulation showed that 91 pairs of chemical components and candidate targets had strong binding efficiencies. The “Jun”, “Chen”, and “Zuo-Shi” herbs from XFZYD triggered their specific targets regulation, respectively. Conclusion. Our work successfully illuminates the “multicompounds, multitargets” therapeutic action of XFZYD in the treatment of TBI by network pharmacology with molecule docking method. The present work may provide valuable evidence for further clinical application of XFZYD as therapeutic strategy for TBI treatment

Cordyceps cicadae Prevents Renal Tubular Epithelial Cell Apoptosis by Regulating the SIRT1/p53 Pathway in Hypertensive Renal Injury

Hypertensive renal injury is a primary etiology of end-stage renal disease, and satisfactory therapeutic strategies are urgently required. Cordyceps cicadae, a traditional Chinese herb, has potential renoprotective benefits and is widely used in the treatment of many kidney diseases. To investigate the mechanisms underlying the renoprotective effect of C. cicadae on hypertensive renal injury, we studied the effect of C. cicadae on tubular epithelial cells (TECs) in a spontaneously hypertensive rat (SHR) model and angiotensin II- (AngII-) cultured primary TECs. Our study showed that C. cicadae treatment could decrease 24-hour urine albumin, albumin-to-creatinine ratio (ACR), β2-MG level, and kidney injury molecule-1 (kim-1) level in SHR urine, alleviate interstitial fibrosis, and reduce α-smooth muscle actin (α-SMA) expression in SHR kidney. In primary TECs, medicated serum containing C. cicadae (CSM) might significantly reduce the AngII-induced production of kim-1 and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, C. cicadae treatment could decrease TEC apoptosis in SHRs as assessed by the terminal transferase-mediated biotin dUTP nick-end labeling (TUNEL) assay. CSM could inhibit caspase-3 activity and enhance cellular viability as measured by methyl thiazolyl tetrazolium in AngII-cultured TECs, suggesting that CSM might reduce the apoptosis level in TECs induced by AngII. We found that the SIRT1 expression level was markedly lowered, while the protein level of acetylated-p53 was elevated in the TECs of patients with hypertensive renal injury and SHRs. C. cicadae presented the effect of regulating the SIRT1/p53 pathway. Further SIRT1 inhibition with EX527 reversed the effect of C. cicadae on AngII-induced apoptosis. Taken together, our results indicate that C. cicadae offers a protective effect on TECs under hypertensive conditions, which may be related to its antiapoptotic effect through regulation of the SIRT1/p53 pathway

Correction: Systematic Review and Meta-Analysis of Detecting Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosing Invasive Aspergillosis.

[This corrects the article DOI: 10.1371/journal.pone.0043347.]

Efficacy of Intermittent or Continuous Very Low-Energy Diets in Overweight and Obese Individuals with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analyses

Objective. This study is aimed at investigating the efficacy of a very low-energy diet (VLED) in overweight and obese individuals with type 2 diabetes mellitus (T2DM). Methods. We thoroughly searched eight electronic resource databases of controlled studies concerning the efficacy and acceptability of intermittent or continuous VLEDs in patients with T2DM compared with other energy restriction interventions. Results. Eighteen studies (11 randomized and seven nonrandomized controlled trials) with 911 participants were included. The meta-analyses showed that compared with a low-energy diet (LED) and mild energy restriction (MER), VLED is superior in the reduction of body weight (mean difference (MD) MDLED=−2.77, 95% confidence interval (CI) CILED=−4.81 to−0.72, PLED=0.008; MDMER=−6.72, 95%CIMER=−10.05 to−3.39, PMER<0.0001), blood glucose (MDLED=−1.18, 95%CILED=−2.05 to−0.30, PLED=0.008; MDMER=−6.72, 95%CIMER=−10.05 to−3.39, PMER<0.0001), and triglyceride (TG) (MDLED=−0.35, 95%CILED=−0.58 to−0.12, PLED=0.002; MDMER=−0.55, 95%CIMER=−0.93 to−0.17, PMER=0.005) levels at the end of the intervention. After the follow-up (1–5 years), no obvious difference in weight loss (MD=−0.84, 95%CI=−3.01 to 1.32, P=0.45, I2=0%) and TG level (MD=−0.25, 95%CI=−0.55 to 0.06, P=0.12, I2=0%) between VLEDs and LEDs was evident, but VLED is more effective in glycemic control (MD=−1.43, 95%CI=−2.65 to−0.20, P=0.02). Compared to bariatric surgery, VLEDs offered comparable effects on weight loss (MD=2.51, 95%CI=−9.52 to 14.54, P=0.37), glycemic control (MD=0.37, 95%CI=−0.22 to 0.96, P=0.22), TG (MD=−0.3, 95%CI=−0.74 to 0.17, P=0.7), and insulin resistance improvement (MD=−1, 95%CI=−2.7 to 0.7, P=0.25). Conclusion. Dietary intervention through VLEDs is an effective therapy for rapid weight loss, glycemic control, and improved lipid metabolism in overweight and obese individuals with T2DM. Thus, VLEDs should be encouraged in overweight and obese individuals with T2DM who urgently need weight loss and are unsuitable or unwilling to undergo surgery. As all outcome indicators have low or extremely low quality after GRADE evaluation, further clinical trials that focus on the remission effect of VLEDs on T2DM are needed

9‑Ethynylfluoroenyl Radicals: Regioselective Dimerization and Post Ring-Cyclization Reactions

9-Ethynylfluorenyl radical derivatives were readily prepared in situ and underwent simultaneous intermolecular coupling reactions. Interestingly, the dimerization process took place in either a head-to-tail or a head-to-head mode between the acetylenic or the allenic resonance forms dependent on the terminal substituents, which could be well explained by their different spin distribution and steric hindrance effects. The structures of the products were confirmed by X-ray crystallographic and other spectroscopic analyses. It was also found that the newly generated dipropinyl dimers underwent a rearrangement and ring-cyclization reaction at room temperature, eventually giving unique difluorenylidene cyclobutene derivatives

Systematic Review and Meta-Analysis of Detecting Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosing Invasive <em>Aspergillosis</em>

<div><h3>Background</h3><p>Bronchoalveolar lavage (BAL) galactomannan (GM) assay has been used for diagnosing invasive <em>aspergillosis</em> (IA). We aimed to derive a definitive estimate of the overall accuracy of BAL-GM for diagnosing IA.</p> <h3>Methods and Results</h3><p>We undertook a systematic review of thirty diagnostic studies that evaluated the BAL-GM assay for diagnosing IA. PubMed and CBM (China Biological Medicine Database) databasees were searched for relevant studies published in all languages up until Feb 2012. The pooled diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) were constructed for each cutoff value. Additionally, pooled sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) were calculated for summarizing overall test performance. Thirty studies were included in this meta-analysis. The summary estimates of pooled DOR, SEN, SPE, PLR, and NLR of the BAL-GM assay (cutoff value 0.5) for proven or probable IA were 52.7 (95% confidence interval (CI) 31.8–87.3), 0.87 (95% CI 0.79–0.92), 0.89 (95% CI 0.85–0.92), 8.0 (95% CI 5.7–11.1) and 0.15 (95% CI 0.10–0.23) respectively. The SROC was 0.94 (95% CI 0.92–0.96). Compared with cutoff value of 0.5, it has higher DOR, SPE and PLR, and similar SEN and NLR with cutoff value of 1.0, which indicated the optimal cutoff value might be 1.0. Compared with BAL-GM, serum GM has a lower SEN and higher SPE, while PCR displays a lower SEN and a similar SPE.</p> <h3>Conclusion</h3><p>With the optimal cutoff value of 1.0, the BAL-GM assay has higher SEN compared to PCR and serum GM test. It is a useful adjunct in the diagnosis of proven and probable IA.</p> </div

para-Quinodimethane- Bridged Perylene Dimers and Pericondensed Quaterrylenes: The Effect of the Fusion Mode on the Ground States and Physical Properties

Polycyclic hydrocarbon compounds with a singlet biradical ground state show unique physical properties and promising material applications; therefore, it is important to understand the fundamental structure/biradical character/physical properties relationships. In this study, para-quinodimethane (p-QDM)-bridged quinoidal perylene dimers 4 and 5 with different fusion modes and their corresponding aromatic counterparts, the pericondensed quaterrylenes 6 and 7, were synthesized. Their ground-state electronic structures and physical properties were studied by using various experiments assisted with DFT calculations. The proaromatic p-QDM-bridged perylene monoimide dimer 4 has a singlet biradical ground state with a small singlet/triplet energy gap (-2.97 kcal mol(-1)), whereas the antiaromatic s-indacene-bridged N-annulated perylene dimer 5 exists as a closed-shell quinoid with an obvious intramolecular charge-transfer character. Both of these dimers showed shorter singlet excited-state lifetimes, larger two-photon-absorption cross sections, and smaller energy gaps than the corresponding aromatic quaterrylene derivatives 6 and 7, respectively. Our studies revealed how the fusion mode and aromaticity affect the ground state and, consequently, the photophysical properties and electronic properties of a series of extended polycyclic hydrocarbon compounds