6-Bromo-2-naphthol from Silene armeria extract sensitizes Acinetobacter baumannii strains to polymyxin.

The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which are resistant to various antibiotics. Combination therapies using natural compounds with antibiotics have been found to have synergistic effects against several pathogens. Synergistic natural compounds can potentiate the effects of polymyxins for the treatment of Acinetobacter baumannii infection. Out of 120 types of plant extracts, only Silene armeria extract (SAE) showed a synergistic effect with polymyxin B (PMB) in our fractional inhibitory concentration and time-kill analyses. The survival rate of G. mellonella infected with A. baumannii ATCC 17978 increased following the synergistic treatment. Interestingly, the addition of osmolytes, such as trehalose, canceled the synergistic effect of SAE with PMB; however, the underlying mechanism remains unclear. Quadrupole time-of-flight liquid chromatography-mass spectrometry revealed 6-bromo-2-naphthol (6B2N) to be a major active compound that exhibited synergistic effects with PMB. Pretreatment with 6B2N made A. baumannii cells more susceptible to PMB exposure in a time- and concentration-dependent manner, indicating that 6B2N exhibits consequential synergistic action with PMB. Moreover, the exposure of 6B2N-treated cells to PMB led to higher membrane leakage and permeability. The present findings provide a promising approach for utilizing plant extracts as adjuvants to reduce the toxicity of PMB in A. baumannii infection.

Effect of nifedipine on the differentiation of human dental pulp cells cultured with mineral trioxide aggregate.

INTRODUCTION: Mineral trioxide aggregate (MTA) can induce differentiation of the dental pulp cells into odontoblast-like cells and generate a dentin-like mineral structure. The mechanisms underlying MTA-induced odontoblastic differentiation in human dental pulp cells (HDPCs) are not completely understood. The purpose of this study was to evaluate the effect of nifedipine as calcium channel blocker on MTA-induced odontoblastic differentiation in HDPCs. METHODS: HDPCs extracted from maxillary supernumerary incisors and third molars were directly cultured on MTA with or without nifedipine in the culture medium. Cell growth and expression of odontoblastic differentiation markers were determined by using methyl-thiazol-diphenyl-tetrazolium assay and reverse transcription-polymerase chain reaction analysis, respectively. Phosphorylation of mitogen-activated protein kinase was measured by Western blotting, and calcium deposition was assessed by using alizarin red S staining. RESULTS: MTA at a concentration of 1 mg/mL significantly up-regulated the expression of dentin sialophosphoprotein and dentin matrix protein-1 and enhanced mineralized nodule formation. However, nifedipine attenuated the MTA-induced odontoblastic differentiation in HDPCs. In addition, MTA-induced mineralization was blocked by inhibition of extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal kinase (JNK) by using U0126, SB203580, and SP600125, respectively. Furthermore, phosphorylation of ERK and JNK in response to MTA was inhibited when the medium was supplemented with nifedipine. CONCLUSIONS: This study showed that calcium ions released from MTA play an important role in odontoblastic differentiation of HDPCs via modulation of ERK and JNK activation.

Effects of acupuncture on c-Fos expression in brain after noxious tooth stimulation of the rat.

Clinically, acupuncture therapy is useful for the control of acute or chronic pain. This study was designed to elucidate the antinociceptive mechanism of acupuncture and the mechanisms underlying cardiovascular reflex elicited by toothache. Expression of c-Fos, a neuronal activation marker, and the phenylethanalamine-N-methyltransferase (PNMT) were examined 1.5 hours after noxious intrapulpal tooth stimulation. Manual acupuncture was performed 20 min before noxious intrapulpal stimulation by 2 M KCl injection into upper or lower anterior tooth pulp. The acupuncture points were Li4 (Hegu) between the 1st and 2nd metacarpal bones or St36 (Zusanli) between the anterior crest of the tibial tuberosity and the fibula head below the patella. After noxious intrapulpal tooth stimulation, Fos-immunoreactive (IR) neurons were identified in the trigeminal subnucleus caudalis (Vc) and the transitional region between the subnucleus caudalis and the subnucleus interpolaris (Vi), in the inferior olivory nucleus (IO) connecting the cerebellum and other brain regions, and also the thalamic ventral posteromedial (VPM) nucleus and centrolateral (CL) nucleus, respectively. In addition, Fos-IR neurons were found in the central cardiovasuclar regulation centers, such as the hypothalamus supraoptic nucleus (SON) and paraventricular nucleus (PVN), and nucleus tractus solitarius (NTS) and rostral ventromedulla (RVLM). All acupuncture at St36 or Li4 significantly suppressed Fos-IR neurons in all Fos-expressed brain areas except the IO nucleus and attenuated the increases in arterial blood pressure (BP) and heart rate (HR) after noxious intrapulpal stimulation. Its Fos-suppressive effects were mostly blocked by naloxone, an opioid antagonist. In addition, acupuncture at St36 or Li4 significantly decreased Fos-containing PNMT, and this effect was also reversed by naloxone. These results suggest that: 1) tooth pulpal noxious signals transmit to the Vc and Vc/Vi transitional region and the 2nd afferent neuron synapse in the thalamic VPM and CL, 2) tooth pulpal pain elicits cardiovascular reflex mediated by NTS, VLM, hypothalamic SON and PVN, and 3) acupuncture reduces cardiovascular reflex elicited by toothache, is associated with the adrenergic system.