Several studies have been conducted to elucidate the role of free fatty acids (FFAs) in the pathogenesis of type 2 diabetes, but the exact molecular mechanism by which FFAs alter glucose metabolism in the liver is still not completely understood. 1 – 4 In a recent publication, Ragheb and coworkers have examined the effect of free fatty acid (FFA) treatment on insulin signaling and insulin resistance by using immunoprecipitation and immunoblotting to study the effect of high concentrations of insulin and FFAs on insulin receptor-beta (IR-β) and downstream elements in the PI3K pathway using the fructose-fed hamster model. 5 Their results clearly show that free fatty acids have an insignificant effect on IR-β and supports previous findings that FFAs lead to insulin resistance in the liver via the PKC-NFκB pathway. 2 , 3

Shimoda and coworkers 1 published a paper on the pharmacological properties of glycosides of the peppery compound capsaicin (1) and its derivative 8-nordihydrocapsaicin (2). In their paper they conclude that the β-glucoside and β-maltoside of 1 and the β-glucoside of 2 still have the same potent anti-obese activity but further studies are needed to determine the physiological effect. Shimoda et al. 1 use glycosylation to make a drug candidate more water soluble to promote their research for new drug candidates within the chemical group of capsaicinoids. Their findings support that this is a plausible way to enhance both bioavailability and “drug-likeliness” properties of drug candidates. This is indeed an interesting approach which should be pursued further and by many more.

This study was undertaken to study the renal toxicity of mercuric chloride in rats at different periods of time. The following groups of rats were studied: i) control, ii) placebo, iii) rats injected with a single ip dose of 100 mg/kg body weight of 2, 3 dimercapto-1-propanesulfonic acid, iv) rats injected with a single ip dose of 100 mg/kg body weight of 2, 3 dimercapto-1-propanesulfonic acid (DMPS) followed by a single dose ip of 2.0 mg HgCl2/kg body weight one hour after DMPS injection v) rats injected with a single ip dose of 2.0 mg HgCl2/kg body weight. Results indicate that mercuric chloride was more toxic after 48 hours of its administration when compared to 24 hours. Mercuric chloride administration caused an impairment of renal function which was evident from a significant decrease in urine volume, urinary excretion of urea, creatinine and glomerular filteration rate (P < 0.001) when compared to other treated groups. There was an increased excretion of protein, albumin and γ–-glutamyltransferase in the urine of mercuric chloride treated rats. Administration of 2, 3 dimercapto-1-propanesulfonic acid before mercuric chloride treatment caused the altered indices to return to near normal levels.

In the current study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor-beta subunit (IR-β), as well as the down stream target in PI3K pathway, total PKB/Akt as well as their phosphorylated forms. The assessment of FFAs treatment showed no direct and significant effect on the PI3K stimulation, specifically the IR-β in primary hepatic control cells treated with insulin. Cells treated with either oleate or palmitate (360 μM) showed no statistically significant values following insulin stimulation (P > 0.05). To further investigate the effect of both FFAs and high insulin (1 μg), we examined the effects of oleate and palmitate at 360 μM concentration on IR-β as well as PKB. There was no significant difference in the total protein levels and their phosphorylated forms in cells treated with or without oleate or plamitate. Interestingly, IR-β tyrosine phosphorylation showed a similar insignificant effect in vivo and ex vivo hepatic cells treated with oleate or palmitate in comparison to their controls in the fructose fed hamsters.

Incubation of methyl 2-benzamidomethyl-3-oxobutanoate with cultured plant cells of Parthenocissus tricuspidata for 2 days afforded methyl (2 R,3 S)-2-benzamidomethyl-3-hydroxybutanoate with 100% de and >99% ee in 51% yield. The use of immobilized cells of P. tricuspidata in calcium alginate gel improved the yield of the product (95% yield) with 100% de and >99% ee. The immobilized cells of P. tricuspidata maintained the high potential for the reduction of methyl 2-benzamidomethyl-3-oxobutanoate (85% yield) after 5 times of usage.

Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role of chelating agents against mercury poisoning, which provides a promising research direction for broader application of chelation therapy in prevention and treatment of mercury poisoning.

Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first cytokine to be evaluated for cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene therapy with inducible or tissue-specific promoters, targeted polymer-DNA complexes, tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion proteins, and peptide/TNF-α fusion proteins have all been investigated to combat cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based therapeutics into clinical investigation.

This introductory editorial hopes to convey three points to its audience. First, it provides an overview of the new, peer-reviewed, open access journal Biochemistry Insights published by Libertas Academica. Second, it summarizes the benefits of open access publishing concepts to the biochemistry community. And third, it takes a brief look at the near future of biochemistry as a fundamental molecular science whose continued advances and latest developments will be the focus of the new journal. Biochemistry Insights looks forward to receiving research articles, review papers, commentaries and letters from all disciplines and specialties of the field.

The purpose of this study was to examine the function of metallothioneins (MT) in respect to the mobilization of heavy metals and superoxide anion (O2–) scavenging in aquatic organisms. Using an O2– generating system, liberation of free zinc from native and zinc MT (Zn-MT) was measured in vitro. Addition of the O2– generating system and H2O2 readily increased the di- and trimeric forms of MT as determined by gel electrophoresis analysis. To determine whether the proportion of oxidized MT could change in contaminated environments, metal-contaminated Mya arenaria clams were collected from a harbour in the St. Lawrence Estuary. The levels of labile zinc, superoxide dismutase (O2– scavenging enzyme), lipid peroxidation (LPO) and the oxidized/metallic form of MT were determined in the digestive gland. The results revealed that the induction of total MT levels was the result of increased oxidized MT at the expense of the reduced or metallic form of MT. Both superoxide dismutase (SOD) and labile zinc (Zn) levels were induced and they were significantly correlated with the oxidized form of MT, but not the metallic form, in feral clam populations. We concluded that the level of total MT was related to Zn mobility and the activation of antioxidant mechanisms such as SOD, and corresponded to the levels of oxidized MT. The metallic form of MT was negatively associated with Zn mobility but positively associated with oxidative damage such as LPO. Overall, the oxidized fraction of MT appeared to be more closely related to detoxification, while the metallic form of MT was associated with metal mobility and toxicity via oxidative damage. The protective effect of MT during heavy-metal contamination depends on the availability of metals and on its capacity to sequester reactive oxygen species.

A reliable and sensitive method of genetic analysis is necessary to detect multiple specific nucleic acid sequences from samples containing limited template. The most widely utilized method of specific gene detection, polymerase chain reaction (PCR), imparts inconsistent results when assessing samples with restricted template, especially in a multiplex reaction when copies of target genes are unequal. This study aimed to compare two methods of PCR product analysis, fluorescent detection following agarose gel electrophoresis or dot blot hybridization with chemiluminescent evaluation, in the detection of a single copy gene (SRY) and a multicopy gene (β-actin). Bovine embryo sex determination was employed to exploit the limited DNA template available and the target genes of unequal copies. Primers were used either independently or together in a duplex reaction with purified bovine genomic DNA or DNA isolated from embryos. When used independently, SRY and β-actin products were detected on a gel at the equivalent of 4-cell or 1-cell of DNA, respectively; however, the duplex reaction produced visible SRY bands at the 256 cell DNA equivalent and β-actin products at the 64 cell DNA equivalent. Upon blotting and hybridization of the duplex PCR reaction, product was visible at the 1–4 cell DNA equivalent. Duplex PCR was also conducted on 186 bovine embryos and product was subjected to gel electrophoresis or dot-blot hybridization in duplicate. Using PCR alone, sex determination was not possible for 22.6% of the samples. Using PCR combined with dot blot hybridization, 100.0% of the samples exhibited either both the male specific and β-actin products or the β-actin signal alone, indicating that the reaction worked in all samples. This study demonstrated that PCR amplification followed by dot blot hybridization provided more conclusive results in the evaluation of samples with low DNA concentrations and target genes of unequal copies.