Transcription factor YY1 is essential for iNKT cell development.

Invariant natural killer T (iNKT) cells develop from CD4+CD8+ double-positive (DP) thymocytes and express an invariant Vα14-Jα18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα14-Jα18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage. YY1-deficient thymocytes underwent normal Vα14-Jα18 gene rearrangements, but exhibited impaired cell survival. Deletion of the apoptotic protein BIM failed to rescue the defect in iNKT cell generation. Chromatin immunoprecipitation and deep-sequencing experiments demonstrated that YY1 directly binds and activates the promoter of the Plzf gene. Thus, YY1 plays essential roles in iNKT cell development by coordinately regulating cell survival and PLZF expression.

Ganoderma lucidum Protects Dopaminergic Neuron Degeneration through Inhibition of Microglial Activation.

Abundant evidence has suggested that neuroinflammation participates in the pathogenesis of Parkinson's disease (PD). The emerging evidence has supported that microglia may play key roles in the progressive neurodegeneration in PD and might be a promising therapeutic target. Ganoderma lucidum (GL), a traditional Chinese medicinal herb, has been shown potential neuroprotective effects in our clinical trials that make us to speculate that it might possess potent anti-inflammatory and immunomodulating properties. To test this hypothesis, we investigated the potential neuroprotective effect of GL and possible underlying mechanism of action through protecting microglial activation using co-cultures of dopaminergic neurons and microglia. The microglia is activated by LPS and MPP(+)-treated MES 23.5 cell membranes. Meanwhile, GL extracts significantly prevent the production of microglia-derived proinflammatory and cytotoxic factors [nitric oxide, tumor necrosis factor-α (TNF-α), interlukin 1ß (IL-1ß)] in a dose-dependent manner and down-regulate the TNF-α and IL-1ß expressions on mRNA level as well. In conclusion, our results support that GL may be a promising agent for the treatment of PD through anti-inflammation.

[Ganoderma lucidum extract protects dopaminergic neurons through inhibiting the production of inflammatory mediators by activated microglia].

Abundant evidence has suggested that neuroinflammation participates in the pathogenesis of Parkinson's disease (PD). The emerging evidence has supported that microglia may play key roles in the progressive neurodegeneration in PD and might be a promising therapeutic target. Ganoderma lucidum (GL), a traditional Chinese medicinal herb, has been shown potential neuroprotective effect in our clinical trials that lead us to speculate that it might possess potent anti-inflammatory and immunomodulating properties. To test this hypothesis, the present study investigated the potential neuroprotective effect of GL and underlying mechanism through inhibiting microglial activation using co-cultures of dopaminergic neurons and microglia. The cultures of microglia or MES23.5 cells alone or together were treated for 24 h with lipopolysaccharide (LPS, 0.25 µg/mL) as a positive control, GL extracts (50-400 µg/mL) or MES23.5 cell membrane fragments (150 µg/mL) were used in treatment groups. Microglia activation, microglia-derived harmful factors and [(3)H]dopamine ([(3)H]DA) uptake of MES23.5 cells were analyzed. The results showed that microglia were activated by LPS and MPP(+)-treated MES23.5 cell membrane fragments, respectively. Meanwhile, GL extracts significantly prevented the production of microglia-derived proinflammatory and cytotoxic factors, including nitric oxide, tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß), in a dose-dependent manner and down-regulated the TNF-α and IL-1ß expressions on mRNA level. In addition, GL extracts antagonized the reduction of [(3)H]DA uptake induced by MPP(+) and microglial activation. In conclusion, these results suggest that GL may be a promising agent for the treatment of PD through anti-inflammation.

[In vitro activity of baicalin against non-albicans Candida biofilms].

OBJECTIVE: To investigate the effects of baicalin against Candida glabrata, C. parapsilosis, C. krusei and C. guilliermondii biofilms. METHOD: 96-well microtitre plates were used to set up the biofilms; microdilution method was applied to detect minimal inhibitory concentration (MIC) of baicalin for the four non-albians Candida, and XTT reduction assay was adopted to determine sessile minimal inhibitory concentration (SMIC) of baicalin against the four isolates and to detect the effects on adhesion of the fungal cells. RESULT: MICs of baicalin for the four non-albians Candida cells were 125, 250, 125, 62.5 mg L(-1), respectively. The four non-albians Candida could form mature biofilms on 96-well microtitre plates. SMIC50 of baicalin for the four isolates were > 1000, 500, 125, 250 mg x L(-1), respectively. SMIC80 for the four isolates were greater than or equal to 1000 mg x L(-1). Baicalin showed potent inhibitory effects on adhesion of the four non-albians Candida cells. CONCLUSION: Baicalin displays substantial inhibitory effects on C. parapsilosis, C. krusei and C. guilliermondii biofilm.

Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development.

The ubiquitously expressed transmembrane adaptor Csk-binding protein (Cbp) recruits Csk to lipid rafts, where the latter exerts its negative regulatory effect on the Src family of protein tyrosine kinases. We have inactivated Cbp in the mouse germ line. In contrast to Csk gene inactivation, which leads to embryonic lethality and impaired T-cell development, Cbp-deficient mice were viable and exhibited normal T-cell development but with an increased thymocyte population. In the absence of Cbp, the amount of Csk that localizes to the lipid rafts was greatly reduced. Interestingly, this altered lipid raft localization of Csk did not lead to any detectable biochemical or functional defect in T cells. The T-cell receptor-induced intracellular calcium flux, cell proliferation, and cytokine secretion were not affected by the absence of Cbp. Peripheral T-cell tolerance to superantigen SEB was also largely intact in Cbp-deficient mice. Thus, Cbp is dispensable for T-cell development and activation.

[Transurethral bipolar plasmakinetic prostatectomy for benign prostatic hyperplasia].

OBJECTIVE: To evaluate the effect and complications of transurethral plasmakinetic prostatectomy (TUPKP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: All 313 patients underwent TUPKP, and the operative indexes and perioperative blood indexes were recorded. After operation, 290, 288 and 142 cases of BPH were followed up at 1 month, 3 months and 1 year respectively. Qmax, IPSS and QOL were measured in all the catamneses. RESULTS: The operative time was (51 +/- 22) min; the mount of blood loss was (66 +/- 60) ml; no TURS occurred in any cases. The mean catheterization time was (11 +/- 10) h and the mean postoperative stay was (3.6 +/- 1.3) d. Qmax increased from (9.0 +/- 4.4) ml/s to (20.5 +/- 7.1) ml/s at 1 month, (21.8 +/- 5.4) ml/s at 3 months and (21.4 +/- 6.6) ml/s at 1 year after operation (P < 0.01). Correspondingly, IPSS decreased from (26.2 +/- 5.1) score to (6.0 +/- 9.0) score, (5.6 +/- 0.8) score and (4.4 +/- 2.7) score (P < 0.01), and the QOL of all the catamneses significantly improved. CONCLUSION: TUPKP, a safe and effective method with fewer complications, can be recommended for the treatment of BPH.