Preventive and therapeutic role of traditional Chinese herbal medicine in hepatocellular carcinoma

AbstractHepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. The clinical management of HCC remains a substantial challenge. Although surgical resection of tumor tissues seems promising, a high recurrence and/or metastasis rate accounting for disease-related death has led to an urgent need for improved postsurgical preventive/therapeutic clinical intervention. Developing advanced target-therapy agents such as sorafenib appears to be the only effective clinical intervention for patients with HCC to date, but only limited trials have been conducted in this regard. Because of their enhanced preventive/therapeutic effects, traditional Chinese herbal medicine (CHM)-derived compounds are considered suitable agents for HCC treatment. The CHM-derived compounds also possess multilevel, multitarget, and coordinated intervention effects, making them ideal candidates for inhibition of tumor progression and HCC metastasis. This article reviews the anticancer activity of various CHMs with the hope of providing a better understanding of how to best use CHM for HCC treatment

EPG2S: Speech Generation and Speech Enhancement based on Electropalatography and Audio Signals using Multimodal Learning

Speech generation and enhancement based on articulatory movements facilitate communication when the scope of verbal communication is absent, e.g., in patients who have lost the ability to speak. Although various techniques have been proposed to this end, electropalatography (EPG), which is a monitoring technique that records contact between the tongue and hard palate during speech, has not been adequately explored. Herein, we propose a novel multimodal EPG-to-speech (EPG2S) system that utilizes EPG and speech signals for speech generation and enhancement. Different fusion strategies based on multiple combinations of EPG and noisy speech signals are examined, and the viability of the proposed method is investigated. Experimental results indicate that EPG2S achieves desirable speech generation outcomes based solely on EPG signals. Further, the addition of noisy speech signals is observed to improve quality and intelligibility. Additionally, EPG2S is observed to achieve high-quality speech enhancement based solely on audio signals, with the addition of EPG signals further improving the performance. The late fusion strategy is deemed to be the most effective approach for simultaneous speech generation and enhancement.Comment: Accepted By IEEE Signal Processing Lette

Voltage-Induced Ca2+ Release in Postganglionic Sympathetic Neurons in Adult Mice.

Recent studies have provided evidence that depolarization in the absence of extracellular Ca2+ can trigger Ca2+ release from internal stores in a variety of neuron subtypes. Here we examine whether postganglionic sympathetic neurons are able to mobilize Ca2+ from intracellular stores in response to depolarization, independent of Ca2+ influx. We measured changes in cytosolic ΔF/F0 in individual fluo-4 –loaded sympathetic ganglion neurons in response to maintained K+ depolarization in the presence (2 mM) and absence of extracellular Ca2+ ([Ca2+]e). Progressive elevations in extracellular [K+]e caused increasing membrane depolarizations that were of similar magnitude in 0 and 2 mM [Ca2+]e. Peak amplitude of ΔF/F0 transients in 2 mM [Ca2+]e increased in a linear fashion as the membrane become more depolarized. Peak elevations of ΔF/F0 in 0 mM [Ca2+]e were ~5–10% of those evoked at the same membrane potential in 2 mM [Ca2+]e and exhibited an inverse U-shaped dependence on voltage. Both the rise and decay of ΔF/F0 transients in 0 mM [Ca2+]e were slower than those of ΔF/F0 transients evoked in 2 mM [Ca2+]e. Rises in ΔF/F0 evoked by high [K+]e in the absence of extracellular Ca2+ were blocked by thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ ATPase, or the inositol 1,4,5-triphosphate (IP3) receptor antagonists 2-aminoethoxydiphenyl borate and xestospongin C, but not by extracellular Cd2+, the dihydropyridine antagonist nifedipine, or by ryanodine at concentrations that caused depletion of ryanodine-sensitive Ca2+ stores. These results support the notion that postganglionic sympathetic neurons possess the ability to release Ca2+ from IP3-sensitive internal stores in response to membrane depolarization, independent of Ca2+ influx

Developing the Effective Method of Spectral Harmonic Energy Ratio to Analyze the Arterial Pulse Spectrum

In this article, we analyze the arterial pulse in the spectral domain. A parameter, the spectral harmonic energy ratio (SHER), is developed to assess the features of the overly decreased spectral energy in the fourth to sixth harmonic for palpitation patients. Compared with normal subjects, the statistical results reveal that the mean value of SHER in the patient group (57.7 ± 27.9) is significantly higher than that of the normal group (39.7 ± 20.9) (P-value = .0066 < .01). This means that the total energy in the fourth to sixth harmonic of palpitation patients is significantly less than it is in normal subjects. In other words, the spectral distribution of the arterial pulse gradually decreases for normal subjects while it decreases abruptly in higher-order harmonics (the fourth, fifth and sixth harmonics) for palpitation patients. Hence, SHER is an effective method to distinguish the two groups in the spectral domain. Also, we can thus know that a “gradual decrease” might mean a “balanced” state, whereas an “abrupt decrease” might mean an “unbalanced” state in blood circulation and pulse diagnosis. By SHER, we can determine the ratio of energy distribution in different harmonic bands, and this method gives us a novel viewpoint from which to comprehend and quantify the spectral harmonic distribution of circulation information conveyed by the arterial pulse. These concepts can be further applied to improve the clinical diagnosis not only in Western medicine but also in traditional Chinese medicine (TCM)

Universal geometrical factor of protein conformations as a consequence of energy minimization

The biological activity and functional specificity of proteins depend on their native three-dimensional structures determined by inter- and intra-molecular interactions. In this paper, we investigate the geometrical factor of protein conformation as a consequence of energy minimization in protein folding. Folding simulations of 10 polypeptides with chain length ranging from 183 to 548 residues manifest that the dimensionless ratio (V/(A)) of the van der Waals volume V to the surface area A and average atomic radius of the folded structures, calculated with atomic radii setting used in SMMP [Eisenmenger F., et. al., Comput. Phys. Commun., 138 (2001) 192], approach 0.49 quickly during the course of energy minimization. A large scale analysis of protein structures show that the ratio for real and well-designed proteins is universal and equal to 0.491\pm0.005. The fractional composition of hydrophobic and hydrophilic residues does not affect the ratio substantially. The ratio also holds for intrinsically disordered proteins, while it ceases to be universal for polypeptides with bad folding properties.Comment: 6 pages, 1 table, 4 figure

Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan

BACKGROUND: Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. METHODS: Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs). RESULTS: Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the 30 STs suggested the serogroup B isolates be assigned into 5 clonally related groups/ clonal complexes and 7 unique clones. The ST-41/44 complex/Lineage 3, and the ST-3439 and ST-3200 groups represented 79% of the serogroup B meningococci. In contrast, isolates within serogroups A, serogroup W135 (and C), and serogroup Y, respectively, simply belonged to ST-7, ST-11, and ST-23 clones. CONCLUSION: Our data suggested that serogroup B isolates were derived from several distinct lineages, most of which could either be indigenous or were introduced into Taiwan a long time ago. The serogroup A, W135 (and C), and Y isolates, respectively, belonged to the ST-7, ST-11, and ST-23, and the represented clones that are currently the major circulating clones in the world and are introduced into Taiwan more recently. The emergence of serogroup A, C and Y strains contributed partly to the increase in cases of meningococcal disease in 2001–2002