The approval of receptor tyrosine kinase (RTK) targeted agent sorafenib as the first effective drug for the systemic treatment of advanced hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. A better understanding of HCC pathogenesis will lead to development of novel targeted treatments. As a typical member of the RTK family, c-Met represents an intriguing target for cancer therapy. The c-Met signaling pathway has been shown to be deregulated and to correlate with poor prognosis in a number of major human cancers. This review discusses the possibility of c-Met as a target in HCC treatment from the following respects: i) c-Met expression and activation profile in HCC, ii) relationship between c-Met and clinicopathologic state and prognosis of HCC, iii) role of c-Met signaling activity in HCC genesis and progression, and iv) strategy of c-Met pathway targeting therapy in HCC treatment.

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In this study, Sesbania grandiflora, a plant in the Leguminosae family, was investigated for its antibacterial activities. The agar well diffusion assay as well as the agar and broth dilution assays were used for determination of antibacterial activities. The crude ethanolic extracts obtained from different parts of this plant exhibited different potent activities. The stem bark has the most potential to yield an extract with the highest antibacterial action. The fractionation of the stem bark with different solvents indicated that the fractionated extracts obtained from ethyl acetate or butanol possessed the most pronounced antibacterial activity. The kinetic study of bactericidal activities revealed that the butanol fractionated extract of the stem bark was effective against Gram negative bacteria. This study suggests that the stem bark of S. grandiflora contains promising antibacterial substances for clinical purposes.

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A polysaccharide was purified from a hot water extract of green tea leaves by measuring the immunostimulatory activity in silkworm larvae. Nuclear magnetic resonance and chemical analysis of acid hydrolysates revealed that the purified substance possessed a backbone containing polygalacturonic acids with methyl ester residues. Treatment with β-glucanase attenuated the muscle contraction activity of the purified sample, suggesting that the β-glucan structure, probably as a branched form, was required for its activity. The purified fraction stimulated the production of interleukin-6 by mouse peritoneal macrophages. These results suggest that measuring immunostimulation in silkworm larvae is useful for evaluating innate immunostimulants from various sources.

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Many pathogenic viruses, such as the influenza virus and the Human Immunodeficiency Virus (HIV)-1, are a threat to humans, thus leading to thousands of deaths annually. The development of antiviral drugs is urgent, and it is an essential strategy for the suppression of these infectious diseases. However, regardless of the rapid emergence of many infectious diseases, the development of novel antiviral drugs has been slow, except for the case of the AIDS. In addition, several viruses can easily mutate and escape the inhibitory activity of anti-viral drugs. It was already well-established that HIV escapes from anti-viral drug effects because of the lack of proofreading activity in its reverse transcriptase. It is known that the influenza virus, which is resistant to Tamiflu, is already spread all over the world. Viruses utilize the host cell environment and cellular factors to propagate. Therefore, the development of novel drugs which inhibit viral protein-host protein interactions or cellular functions appear to be good candidates. The influenza virus is unique in replicating in host nuclei, and we therefore focused on the nuclear export processes for the development of anti-influenza viral drugs. We previously reported that leptomycin B (LMB), which inhibited the nuclear export processes via the nuclear export signal (NES) inhibited the nuclear export of influenza viral RNP (vRNP), and resulted in the inhibition of influenza viral propagation. We herein examined novel CRM1 inhibitors, valtrate from Valerianae Radix, and 1'-acetoxychavicol acetate (ACA) from Alpinia galanga as potent inhibitors for the influenza virus replication.

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Amino acids exert nephroprotective effects in various forms of acute renal injury depending on their renal hemodynamic effects. The present study was designed to elucidate and compare the role of non hemodynamic mechanisms in protective actions afforded by glycine and L-arginine against cisplatin (CDDP)-induced nephrotoxicity using rat renal cortical slices (RCS). We have investigated the possible modulatory effect of glycine and L-arginine on oxidative stress and necrosis induced by CDDP as well as on CDDP uptake by kidney. After 4 h of incubation with 2 mM CDDP, nephrotoxicity was demonstrated by significant increased lactate dehydrogenase leakage, decreased ability of the slices to reduce 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide, increased lipid peroxides and depleted reduced glutathione. Also, CDDP significantly inhibited pyruvate-stimulated gluconeogenesis. Histopathological examination of RCS confirmed the occurrence of tubular coagulative necrosis in cortex and corticomedullary regions. Preincubation of RCS with 1 mM glycine or L-arginine 1 h before CDDP addition significantly attenuated the oxidative stress and tubular necrotic effects of CDDP. L-Arginine showed greater antioxidant properties while glycine showed a greater antinecrotic effect. Moreover, the nephroprotective effect was mediated through lowering the platinum uptake by RCS. However, they could not counteract the inhibition of gluconeogenesis induced by CDDP. In conclusion, the present study sheds light on the mechanisms involved in glycine and L-arginine nephroprotection.

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Four accurate, precise, rapid, reproducible, and simple spectrophotometric methods were validated for determination of repaglinide (RPG), pioglitazone hydrochloride (PGL) and rosiglitazone maleate (RGL). The first two methods were based on the formation of a charge-transfer purple-colored complex of chloranilic acid with RPG and RGL with a molar absorptivity 1.23 × 10³ and 8.67 × 10² l•mol⁻¹•cm⁻¹ and a Sandell's sensitivity of 0.367 and 0.412 μg•cm⁻², respectively, and an ion-pair yellow-colored complex of bromophenol blue with RPG, PGL and RGL with molar absorptivity 8.86 × 10³, 6.95 × 10³, and 7.06 × 10³ l•mol⁻¹•cm⁻¹, respectively, and a Sandell's sensitivity of 0.051 μg•cm^-2 for all ion-pair complexes. The infl uence of different parameters on color formation was studied to determine optimum conditions for the visible spectrophotometric methods. The other spectrophotometric methods were adopted for demtermination of the studied drugs in the presence of their acid-, alkaline- and oxidativedegradates by computing derivative and pH-induced difference spectrophotometry, as stability-indicating techniques. All the proposed methods were validated according to the International Conference on Harmonization guidelines and successfully applied for determination of the studied drugs in pure form and in pharmaceutical preparations with good extraction recovery ranges between 98.7-101.4%, 98.2-101.3%, and 99.9-101.4% for RPG, PGL, and RGL, respectively. Results of relative standard deviations did not exceed 1.6%, indicating that the proposed methods having good repeatability and reproducibility. All the obtained results were statistically compared to the offi cial method used for RPG analysis and the manufacturers methods used for PGL and RGL analysis, respectively, where no signifi cant differences were found.

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Matrix type transdermal therapeutic systems (TTS) of glibenclamide were formulated using polymers Eudragit RL 100, ethyl cellulose, PVP K-30, and polyvinyl acetate, and citral was used as the penetration enhancer. The polymer fi lms were formulated with Eudragit RL 100 and PVP K-30 in different ratios and subsequently subjected to ex vivo studies (drug permeation through rat skin) followed by interaction studies, skin irritation studies, accelerated stability analysis, and in vivo studies (determination of blood glucose level in rabbits). The drug content of the formulations was found to be 99.1-99.2%. The cumulative percentages of drug permeated through rat skin from the three selected formulations in 48 h were 95.3%, 98.8%, and 99%, respectively. A plot between cumulative percent of drug permeated and square root of time exhibited linear curves, which suggests the Higuchian matrix mechanism of drug release. The formulation containing Eudragit RL 100 and PVP K-30 showed better improvement in hypoglycemic activity in rabbits (56.2-60.8% reduction in blood glucose level, p < 0.05). There were fewer fluctuations in blood glucose level as compared to oral therapy due to controlled release of the active pharmaceutical ingredient, and no interaction was found between the drug and excipients of the formulation. Accelerated stability analysis showed that the formulation was stable up to 5.5 years, with negligible skin irritation. The formulation precluded severe hypoglycemic reactions (side effect of sulfonylureas) and was effective for management of diabetes mellitus up to 48 h, with a single TTS.

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