Asymmetric synthesis of cyclopropyl-fused 2'-C-methylcarbanucleosides as potential anti-HCV agents

Novel 2'-C-methyl-cyclopropyl-fused carbocyclic nucleosides as potential anti-HCV agents were stereoselectively synthesized, utilizing regioselective cleavage of the isopropylidene group and cyclic sulfate chemistry as key steps.     

Stereoselective synthesis of homo-apioneplanocin A as potential inhibitor of S-adenosylhomocysteine hydrolase

Homo-apioneplanocin A (1) as a potential inhibitor of S-adenosylhomocysteine hydrolase was synthesized from D-ribose, employing stereoselective hydroxymethylation, regioselective oxidation, and regio- and chemoselective hydroboration as key steps.     

C<Subscript>6</Subscript>-ceramide enhances phagocytic activity of Kupffer cells through the production of endogenous ceramides

Ceramide has been suggested to be not only a tumorsuppressive lipid but also a regulator of phagocytosis. We examined whether exogenous cell-permeable C₆-ceramide enhances the phagocytic activity of Kupffer cells (KCs) and affects the level of cellular ceramides. Rat KCs were isolated by collagenase digestion and differential centrifugation, using Percoll system. Phagocytic activity was measured by FACS analysis after incubating KCs with fluorescence-conjugated latex beads, and the level of cellular ceramide was analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). In this study we found that permeable C₆-ceramide increases the cellular levels of endogenous ceramides via a sphingosine-recycling pathway leading to enhanced phagocytosis by KCs.     

A serum protein profile predictive of the resistance to neoadjuvant chemotherapy in advanced breast cancers

Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies.     

Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function

Systemic transplantation of adipose-derived stem cells (ASCs) is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues. This study investigated the effects of systemic transplantation of human ASCs (hASCs) on bone repair. We found that hASCs secrete various bone cell-activating factors, including hepatocyte growth factor and extracellular matrix proteins. Systemic transplantation of hASCs into ovariectomized mice induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss. We also observed that conditioned medium from hASCs is capable of stimulating proliferation and differentiation of osteoblasts via Smad/extracellular signal-regulated kinase (ERK)/JNK (c-jun NH(2) -terminal kinase) activation as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation in vitro. Overall, our findings suggest that paracrine factors secreted from hASCs improve bone repair and that hASCs can be a valuable tool for use in osteoporosis therapy.     

Potential agents for cancer and obesity treatment with herbal medicines from the green garden

Many classes of bioactive drug-like molecules derived from traditional herbal plants are becoming attractive as alternative medicines for the treatment of severe chronic diseases such as cancer and obesity. A set of chemically synthesized drugs that is capable of both inhibiting cancer growth and reducing body weight for treatment of obesity have severe side effects including nausea, vomiting, diarrhea as well as producing increased blood pressure and headache, respectively. For decades, drug candidates from herbal plants have been considered as potential therapeutic agents because they are generally safer, less toxic, and have fewer lethal side effects than chemically synthesized or semi-synthetic drugs. Understanding the key factors affecting pharmacological effects and clinical outcomes has been a critical theme of natural product research. However, standardized sample preparation methods, well-controlled scientific studies, and validation studies are needed before herbal therapeutics can be introduced into the global market. This review will address the current advances in using traditional herbal plants, including the pharmacological effects and the challenges faced during the development of new drugs. The safety issues associated with toxicity and the effectiveness of the herbs in specific diseases such as cancer and obesity are also discussed.