SDS对SB3-12胶束表面电荷密度的调控作用及对药物增溶的影响

两性离子甜菜碱表面活性剂(SB3-12)胶束具有较好的生物相容性,由于相反电荷的极性头之间具有静电中和作用,胶束表面具有小的负电荷密度。当加入阴离子的十二烷基硫酸钠(SDS)以后,负离子SD-与SB3-12胶束极性区内层季铵正电荷的静电中和作用,能连续地调节胶束表面磺酸基的负电荷密度,这有利于对药物分子的选择性增溶和调节在生理条件下的药物的输送。等温滴定量热(ITC)研究发现SB3-12和SDS有强的协同效应,混合临界胶束浓度(CMC)和胶束化焓明显降低,并得到两者协同效应的弱静电作用机理。当模型药物分子芦丁(Rutin)与SB3-12/SDS混合胶束作用时,芦丁7位羟基的氢解离后的阴离子与SDS共同作用于SB3-12形成混合胶束。UV-Vis吸收光谱和~1H NMR谱研究发现,在SB3-12胶束中,芦丁分子的A环位于季铵阳离子附近,B环位于两个相反电荷之间的弱极性区域。在SDS胶束中,B环位于栅栏层,而A环和二糖暴露于水相侧。在混合胶束中,随着SDS摩尔分数增加,对A环的静电吸引变弱。离子表面活性剂对两性离子表面活性剂胶束表面电荷密度的调节作用,本质上是对胶束极性区域的物理及化学性质的微调,进而实现对药物的可控增溶。

Correlation between the cumulative analgesic effect of electroacupuncture intervention and synaptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica

In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanfi （ST36） and Yanglingquan （GB34）. In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold （paw withdrawal latency） was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanfi and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus.

The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region

In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanfi （ST36） and Yanglingquan （GB34） once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold （paw withdrawal latency） was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptJc cleft width and thinning of the postsynaptJc density, and it significantly suppressed the down-regulation of intracellular calcium/ calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kJnase II expression in the hippocampal CA3 region.

Retrospective analysis of patients with rare-site and metastatic giant cell tumor

A giant cell tumor occurs mainly in the proximal tibia,humerus,distal radius bone and the pelvic bone.It is rarely observed in such sites as the ribs and the temporal bone.The condition is primarily treated with surgical excision and functional reconstruction.The effect of chemotherapy on lung metastases and locally advanced giant cell tumors has remained unknown.We collected and analyzed the data of six patients with rare giant cell tumors located in the head and neck patients.After an average follow-up of 42.6 months after surgery （14 to 90 months）,no local recurrence or metastasis was observed.We also collected and analyzed the data of five patients with metastatic giant cell tumors who were undergoing surgery for the primary tumor before; of three patients who had experienced multiple chemotherapy cycles,one had spontaneous regression,and one survived for long timer despite progression.The other two patients had their major metastatic lesions resected by surgery,and presented long-term survival during the follow up.In addition,this study reports one patient with locally advanced giant cell tumor of the rib,who has undergone successful surgical resection following two cycles of chemotherapy with ifosfamide and liposomal doxorubicin.Complete resection of the lesion at the head and neck is the key to relapse-free survival.The prognosis of lung metastases in patients with giant cell tumors is relatively satisfying.Neoadjuvant chemotherapy is also conducive to the surgery for locally advanced lesions and improvement of the quality of life.

Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

Objective In this study, we evaluated the difference of progression-free survival(PFS) and overall survival(OS) between extensive-stage small-cell lung cancer(ES-SCLC) patients who acquired partial response(PR) or complete remission(CR) after two cycles of first-line chemotherapy with the etoposide plus cisplatin(EP) regimen and those who acquired PR or CR after four or six cycles.Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region(China) between November 2004 and May 2011, were enrolled in this study. RECIST version 1.1 was used for the evaluation of chemotherapy efficiency. We followed up all eligible patients every 4 weeks. All statistical data were analyzed by using SPSS 21.0 statistical package for Windows.Results After a median follow-up of 293 days(range, 62–1531 days), all patients had died by the cutoff date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months(95% CI, 5.1–6.9), and the median OS was 10.5 months(95% CI, 8.6–12.4). Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months(95% CI, 4.4–5.2), and the median OS was 7.5 months(95% CI, 6.8–8.2). Both PFS and OS showed a statistical difference between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.

Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation

Many G protein-coupled receptors （GPCRs） are reported to be involved in the pathogenesis of multiple sclerosis （MS）, and -40% of all identified GPCRs rely on the Gaq/11 G protein family to stimulate inositol lipid signaling. However, the function of Ga subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gaq in the pathogenesis of experimental autoimmune encephalomyelitis （EAE）, a well-known mouse model of MS. We discovered that compared with wild-type mice, Gaq-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination. Moreover, a significantly lower percentage of Th17 cells, one of the key players in MS pathogenesis, was observed in Gaq-knockout EAE mice. Studies in vitro demonstrated that deficiency of Gaq in CD4＋ T cells directly impaired Th17 differentiation. In addition, deficiency of Gaq significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the Gaq-PLCβ-PKC and Gaq-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of Gaq in regulating Th17 differentiation and MS oathogenesis.

Seasonal variations of tris (2-chloroethyl) phosphate and cytotoxicity of organic extracts in water samples from Wuhan, China

Tris(2-chloroethyl) phosphate(TCEP) is a typical phosphate flame retardant. Its potential adverse health effects have recently aroused concern. We investigated the seasonal variations of TCEP concentrations in the raw, finished and tap water samples from two drinking water treatment plants(DWTPs) in China, and evaluated the cytotoxicity and apoptosis/necrosis of organic extracts(OEs) in water samples. We enriched TCEP and OEs in water samples by solid-phase extraction method. The TCEP concentrations in water samples were determined by gas chromatography–mass spectrometry. Normal human liver cell line L02 was treated with OEs in the water samples, and then the cytotoxicity and apoptosis/necrosis were measured by 3-(4, 5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and flow cytometry, respectively. The results showed that cytotoxicities of OEs in raw water samples from both DWTPs in summer and winter were stronger than those in spring and autumn, cytotoxicity of OEs in finished and tap water samples from both DWTPs in summer and autumn were stronger than those in spring and winter. In all seasons, the maximal concentrations(100 mL water/mL cell culture) of OEs in the raw water samples from both DWTPs induced late apoptosis/necrosis. The reasons for seasonal variations of TCEP in water samples and potential toxic effects of other pollutants in the water samples need to be further investigated.