Impact of drug discovery on stem cell biology

Despite the rapid technical progress in pharmaceutical industry in the past decade, it is still a great challenge to find new drugs and the situation seems more and more serious. However, the history of pharmaceutical industry clearly indicated that the significance of drug discovery went far beyond providing new drugs. For instance, drugs or candidates could be used as selective probes to reveal novel cellular mechanisms, which is a fundamental tenet of chemical biology. More interestingly, accumulating evidence indicates that drugs and candidates can find important use in stem cell biology. Not only approved drugs but also undeveloped pharmacological agents could serve as efficient agents to regulate stem cell fate. Moreover, the target and activity knowledge accumulated during the drug discovery process will help select the stem cell fate modulators in a rational manner. As the progress in stem cell biology will bring positive influence to drug discovery, it can be expected that the current drug discovery efforts will finally bear great fruits in the future.     

Virucidal Nanofiber Textiles Based on Photosensitized Production of Singlet Oxygen

Novel biomaterials based on hydrophilic polycaprolactone and polyurethane (Tecophilic®) nanofibers with an encapsulated 5,10,5,20-tetraphenylporphyrin photosensitizer were prepared by electrospinning. The doped nanofiber textiles efficiently photo-generate O₂(¹Δ_g), which oxidize external chemical and biological substrates/targets. Strong photo-virucidal effects toward non-enveloped polyomaviruses and enveloped baculoviruses were observed on the surface of these textiles. The photo-virucidal effect was confirmed by a decrease in virus infectivity. In contrast, no virucidal effect was detected in the absence of light and/or the encapsulated photosensitizer.     

Genistein Suppresses LPS-Induced Inflammatory Response through Inhibiting NF-κB following AMP Kinase Activation in RAW 264.7 Macrophages

Genistein, the major isoflavone in soybean, was recently reported to exert beneficial effects in metabolic disorders and inflammatory diseases. In the present study, we investigated the effects and mechanisms of a dietary concentration of genistein on the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results demonstrated that genistein effectively inhibited the LPS-induced overproduction of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), as well as LPS-induced nuclear factor kappa B (NF-κB) activation. In addition, the data also showed that genistein prevented LPS-induced decrease in adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. These effects were obviously attenuated by an AMPK inhibitor. Taken together, our results suggest that the dietary concentration of genistein is able to attenuate inflammatory responses via inhibition of NF-κB activation following AMPK stimulation. The data provide direct evidence for the potential application of low concentrations of genistein in the prevention and treatment of inflammatory diseases.     

Reproductive competition between females in the matrilineal Mosuo of southwestern China

The matrilineal Mosuo of southwestern China live in communal households where brothers and sisters of three generations live together (duolocal residence), and men visit their wives, who reside elsewhere, only at night in ‘visiting’ marriages. Here we show that these communally breeding sisters are in reproductive conflict, in the sense that they share the resources needed to reproduce. We analyse determinants of reproductive success in females and males, and show that co-resident female kin are in competition; the more female kin reside in the household, the more reproductive success is reduced. Male reproductive success, however, is not determined by the kin in his natal household; duolocal males are not in reproductive conflict with their siblings. Competition with female cousins can be worse than that between sisters. We also find that female work on the farm (which is the main communal resource) is not equal. We use a ‘tug-of-war’ model of reproductive skew generated by incomplete control, to model the patterns of effort put into competition between sisters and cousins. The model predicts that more dominant (older) sisters will put less effort into reproductive conflict than will less dominant (younger) sisters; but younger sisters will also have lower reproductive success because they are less efficient at gaining access to the shared resource. Both predictions are consistent with our data. Younger sisters work less in the fields than do older sisters, which may represent a form of conflict or may be because their average relatedness to the household is lower than that of their more fertile older sisters.     

α‐ketoglutarate delays age‐related fertility decline in mammals

The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α‐ketoglutarate (α‐KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α‐KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α‐KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α‐KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down‐regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α‐KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.