Depletion of vesicular zinc in dorsal horn of spinal cord causes increased neuropathic pain in mice

Zinc enriched (ZEN) neurons and terminals are abundant in the rodent spinal cord. Zinc ions have been suggested to modulate the excitability of primary afferent fibers believed to be important in nociceptive transmission. To test the hypothesis that vesicular zinc concentration is related to neuropathic pain we applied Chung’s rodent pain model on BALB/c mice, and traced zinc transporter 3 (ZnT3) proteins and zinc ions with immunohistochemistry and autometallography (AMG), respectively. Under anesthesia the left fifth lumbar spinal nerve was ligated in male mice in order to produced neuropathic pain. The animals were then sacrificed 5 days later. The ZnT3 immunoreactivity was found to have decreased significantly in dorsal horn of fourth, fifth, and sixth lumbar segments. In parallel with the depressed ZnT3 immunoreactivity the amount of vesicular zinc decreased perceptibly in superficial gray matters of especially layer I-IV of the same segments. The transection-induced reduction of vesicular zinc in ZEN terminals of the dorsal horn was synchronic to reduced pain threshold, as measured by von Frey method. In a separate study, we observed intensive zinc selenite precipitation in somata of the smaller spinal ganglion cell, but 5 days after spinal nerve transection zinc precipitation was also found in the lager ganglion cells. The present results indicate that zinc may be involved in pain mechanism in the spinal ganglion level. These results support the hypothesis that vesicular zinc might have a modulatory role for neuropathic pain. Thus, increased pain sensitivity might be related to reduce vesicular zinc level in the dorsal spinal gray matter.     

Heparin-binding epidermal growth factor-like growth factor inhibits adipocyte differentiation at commitment and early induction stages

Abstract Adipocytokines, bioactive molecules secreted from adipose tissues, play important roles in physiology, development, and disease. Recently, heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified as an adipocytokine whose expression correlates with obesity. However, the biological role of fat-secreted HB-EGF is still unclear. In this study, we investigated the effects of HB-EGF on the adipocyte differentiation of C3H10T1/2 pluripotent mesenchymal cells. Upon adipogenic conversion of C3H10T1/2 cells, HB-EGF displayed dynamic changes in expression where an initial decrease was followed by increased levels of expression at later stages. HB-EGF treatment during adipogenic induction inhibited lipid accumulation and decreased the expression of adipocyte molecular markers (fatty acid-binding protein, peroxisome proliferator-activated receptor γ, and CAAT enhancer-binding protein α) and lipogenic genes (glucose transporter, fatty acid synthetase, and lipoprotein lipase). Therefore, HB-EGF has an inhibitory effect on adipocyte differentiation. Administration of HB-EGF at various intervals during adipocyte differentiation revealed that HB-EGF acts during the early stages of adipocyte differentiation, but not at the later stages of differentiation. Furthermore, HB-EGF was able to block the commitment of pluripotent mesenchymal cells to the adipocyte lineage triggered by bone morphogenic protein 4 treatment. These data suggest that HB-EGF acts as a negative regulator of adipogenesis by inhibiting the commitment and early differentiation of the adipose lineage. The inhibitory role of HB-EGF on adipocyte differentiation of pluripotent mesenchymal cells sheds light on potential mechanisms that control adipose tissue homeostasis.     

Innate immune stimulation of exo-polymers prepared from <Emphasis Type="Italic">Cordyceps sinensis</Emphasis> by submerged culture

After we prepared exo-polymers (EPS) from Cordyceps sinensis by submerged culture, prophylactic intravenous administration (i.v.) of EPS significantly inhibited metastasis in experimental lung metastasis of colon 26-M3.1 carcinoma. Cytotoxicity against Yac-1 tumor cells of natural killer (NK) cell, which was prepared by i.v. of EPS (100 μg/mouse), significantly augmented 2 days after EPS treatment. When NK cells were depleted by rabbit anti-asialo GM1 serum, even the EPS group totally abolished the inhibitory effect on lung metastasis of colon 26-M3.1 cells. EPS can stimulate innate immune system to inhibit tumor metastasis, and its anti-tumor metastasis is associated with macrophage and NK cell activation.     

Potent, low-calcemic, selective inhibitors of CYP24 hydroxylase: 24-sulfone analogs of the hormone 1alpha,25-dihydroxyvitamin D3

The new 24-phenylsulfone 4a, a low-calcemic analog of the natural hormone 1alpha,25-dihydroxyvitamin D(3), is a potent (IC(50) = 28nM) and highly selective inhibitor of the human 24-hydroxylase enzyme CYP24.     

Cloning of the fibroin gene from the oak silkworm, Antheraea yamamai and its complete sequence

The nucleotide sequences containing an entire genomic region and 5 upstream region of Antheraea yamamai fibroin gene have been determined. The gene consists of an initial exon encoding 14 amino acids, an intron (150 bp), and a long second exon coding for 2641 amino acids. The fibroin coding sequence shows a specialized organization with a highly repetitive region flanked by non repetitive 5 and 3 ends. Northern blot analyses confirmed that fibroin gene is actively expressed in the posterior silk gland of the final instar larvae of Antheraea yamamai.     

Biphasic poroviscoelastic simulation of the unconfined compression of articular cartilage: II--Effect of variable strain rates

This study investigated the abilities of the linear biphasic poroviscoelastic (BPVE) model and the linear biphasic poroelastic (BPE) model to simulate the effect of variable ramp strain rates on the unconfined compression stress relaxation response of articular cartilage. Curve fitting of experimental data showed that the BPVE model was able to successfully account for the ramp strain rate-dependent viscoelastic behavior of articular cartilage under unconfined compression, while the BPE model was able to account for the complete viscoelastic response at a slow strain rate, but only the long-term viscoelastic response at faster strain rates. We concluded that the short-term viscoelastic behavior of articular cartilage, when subjected to a fast ramp strain rate, is primarily governed by a fluid flow-independent (intrinsic) viscoelastic mechanism, whereas the long-term viscoelastic behavior is governed by a fluid flow-dependent (biphasic) viscoelastic mechanism. Furthermore, a linear viscoelastic representation of the solid stress was found to be a valid model assumption for the simulation of ramp strain rate-dependent relaxation behaviors of articular cartilage within the range of ramp strain rates investigated.     

Cultivation of a cyanobacterium in an internally radiating air-lift photobioreactor

This study proposes a new design of the internally radiatingphotobioreactor, which combines the advantages of an air-lift bioreactorand an internally radiating system, and an efficient way of supplying lightenergy into the photobioreactor during cell cultivation. For a modelphotosynthetic microorganism, Synechococcus PCC 6301 wascultivated in an internally radiating air-lift photobioreactor. The lightcondition inside the photobioreactor was characterized by the average lightintensity which was calculated from the light distribution model. Sinceexcessive light energy induced photoinhibition at the early growth stage, thestrategy of lumostatic operation was developed in order to maintain thelight condition at an appropriate level during cell cultivation. Based on thecalculation results of the light distribution model, the average light intensitywas regulated at 30, 60, or 90 mol m^-2 s^-1 byincreasing the number of light radiators. The model-based control ofirradiating level enabled us to harvest a larger amount of cells withoutshowing the photoinhibited growth. Other favorable results included thereduction of cultivation time and lower consumption of irradiating power.     

Synthesis and antiviral activity of novel D- and L-2'-azido-2',3'-dideoxyribofuranosyl-4'-thiopyrimidines and purines

Novel D- and L-2'-azido-2',3'-dideoxyribofuranosyl-4'-thiopyrimidines and purines have been synthesized starting from L-xylose and D-xylose, respectively. Among synthesized compounds tested against several viruses such as HIV-1, HSV-1, HSV-2, and HCMV, D-beta-N6-methyladenine (ent-22a) and D-alpha-N6-methyladenine (ent-22b) analogues were found to exhibit significant anti-HCMV activity.     

Synthesis of pyridino[2,3-f]indole-4,9-dione and 6,7-disubstituted quinoline-5,8-dione derivatives and evaluation on their cytotoxic activity

We report upon the synthesis of the following derivatives: N-substituted-pyridino[2,3-f]indole-4,9-dione, and 6-(alpha-diethoxycarbonyl-methyl)-7-substituted-amino-quinoline-5,8-dione, which contain the active quinoline-5,8-dione (VII) moiety. The cytotoxic activities of these compounds have been tested in SRB (SulfoRhodamine B) assays against the cancer cell lines of A-549 (human lung cancer), SK-MEL-2 (human melanoma cancer), SK-OV-3 (human ovarian cancer), XF-498 (human brain cancer) and HCT 15 (human colon cancer). The compound, N-benzyl-3-ethoxycarbonyl-2-hydroxy-pyridino[2,3-f]indole-4,9-dione (A-9), also showed higher activity than cis-platin. The highest level of cytotoxic activity in these human tumor cell lines was observed in the compound 6-(alpha-diethoxycarbonyl-methyl)-7-(2-methyl-phenylamino)-quinoline-5,8-dione (B-3).