[Effects of recipes for replenishing qi and activating blood on senescence related gene expressions in the liver of aging rats].

OBJECTIVE: To observe the effects of recipes for replenishing qi and activating blood on p16, p21, proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E gene expressions in the liver of aging rats. METHODS: A recipe for replenishing qi and a recipe for activating blood were administered to aging rats respectively, and the effects of the above recipes on the expressions of senescence related genes (p16, p21, PCNA, cyclin D1 and cyclin E) were examined by RT-PCR and Western blotting methods. RESULTS: The expressions of p16, p21 and cyclin D1 mRNAs and proteins in the liver of the untreated aging rats were up-regulated, while the expressions of PCNA and cyclin E mRNAs and proteins decreased. As compared with the untreated aging rats, both recipes could down-regulate the expressions of cyclin D1 mRNA and protein and up-regulate the expressions of cyclin E mRNA and protein, but had no obvious effects on the expressions of mRNAs and proteins of p16, p21 and PCNA. CONCLUSION: Recipes for replenishing qi and activating blood can improve the liver cell proliferation of aging rats via down-regulating the expressions of cyclin D1 mRNA and protein and up-regulating the expressions of cyclin E mRNA and protein.

HSF1 blockade-induced tumor thermotolerance abolishment is mediated by JNK-dependent caspase-3 activation.

We previously blocked the heat shock transcription factor 1 function with a dominant-negative mutant (mHSF1) in breast cancer cell line Bcap37, and found that mHSF1 sensitizes Bcap37 cells to hyperthermia by promoting the apoptotic process. Here we studied the mechanism of this abolishing process and how thermotolerance develops in Bcap37 cells. The results indicated that mHSF1 abolished acquired or intrinsic thermotolerance in Bcap37 cells by enhancing JNK and caspase-3 pathways, two stress-induced apoptotic pathways, after hyperthermia, and interference with either one of them attenuated hyperthermia-induced apoptosis. Furthermore, epistasis assay of these two pathways suggested that JNK was upstream of the caspase-3 pathway. Conversely, other hyperthermia-induced kinases implicated in cell survival and death, Akt, ERK or p38, did not influence the effect of mHSF1, indicating that these kinases were not implicated in this abolishing process. In addition, we found that the development of acquired thermotolerance of Bcap37 cells was associated with the suppression of JNK activation after mild preheat treatment and was not reduced by Akt, ERK or p38 inhibition. In contrast, the intrinsic thermotolerance of Bcap37 cells was due to the intrinsic high levels of Akt and ERK activities since Akt or ERK inhibition resulted in increased thermosensitivity of Bcap37 cells. Our results suggest that mHSF1 plays a valuable role in the thermotolerance abolishment of Bcap37 cells, which likely contributes to tumor therapy in combination with hyperthermia.

Relationship between apolipoprotein E and apolipoprotein B polymorphisms in youths with coronary heart disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate hereditary susceptibility to coronary heart disease (CHD) in apolipoprotein E(apo E) and apo B polymorphisms of youths.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze apoE, apoB Xba I, apoB 3' variable number of tandem repeat (VNTR) genotypes for 244 healthy Han students (among them were 109 students with positive CHD family history).</p><p><b>RESULTS</b>The allele frequencies of apo e4, XbaI x(+), 3'VNTR-B(hypervariable element, HVE>38) in the positive group were obviously higher than those in the negative group(P<0.05), and were significantly correlated with the increase in TC, LDL-C, apoB100 levels (P<0.05).</p><p><b>CONCLUSION</b>The alleles for apo e4, XbaI x(+), 3'VNTR-B may be the important genetic markers of Han CHD.</p>

Interleukin-2 gene has superior antinociceptive effects when delivered intrathecally.

The antinociceptive effect of interleukin-2 gene on rat carrageenan-induced pain was explored using different delivery methods. Intrathecal (i.t.) or plantar s.c. delivery of plasmid harbouring the interleukin-2 gene produced a marked antinociceptive effect, which was maintained up to 6 days; the administration of recombinant human interleukin-2 only had a transitory effect. The antinociceptive effect lasted longer and was more potent when the interleukin-2 gene was administered i.t. than when delivered s.c. The effect of the interleukin-2 gene was related to its protein expression, was dose dependent, and could be potentiated by liposome. The results suggest that the interleukin-2 gene has a good prospect for clinical use.

Blocking HSF1 by dominant-negative mutant to sensitize tumor cells to hyperthermia.

Heat shock protein 70 (HSP70), an antiapoptotic chaperon protein, is highly expressed in human breast tumors and renders them resistant to such therapy as hyperthermia. In the present study, we inhibited the expression of HSP70 by blocking the heat shock transcription factor 1 (HSF1) function with its dominant-negative mutant (mHSF1) in Bcap37 cells, a thermotolerant breast cancer cell line. Here we report that retrovirus-mediated transfer of mHSF1 led to massive cell death of Bcap37 after hyperthermia. mHSF1 sensitized Bcap37 cells to hyperthermia by promoting apoptosis induced by heat shock. We also examined the efficacy of mHSF1 gene therapy in the nude mouse. mHSF1 transfection led to diminution of tumor growth with hyperthermia therapy. Thus, disrupting HSF1 in combination with hyperthermia may open new possibilities for treatment of cancers that have acquired resistance to heat treatment.