Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

BACKGROUND: Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. METHODS: We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. RESULTS: At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. CONCLUSIONS: Our results provide direct evidence that tremor in the upper extremity of patients with PD can be inhibited to a large extent with evoked cutaneous reflexes via surface stimulation of the dorsal hand skin area innervated by the superficial radial nerve.

Dihydroartemisinin: a new story of an old drug against Schistosoma mansoni infection.

Currently, praziquantel is the drug of choice for the treatment of human Schistosoma mansoni infections. It has not been proved until now that there is real praziquantel resistance, but there is decreased praziquantel sensitivity. A search for novel antischistosomal agents against the parasite has been given a high priority. Dihydroartemisinin, formerly identified as an antimalarial drug, has been shown to be active against both Schistosoma japonicum and S. mansoni in mice. Interestingly, dihydroartemisinin is found to be highly effective against the 14-28-day schistosomula of S. mansoni, and treatment with multiple low doses of the drug achieves a high efficacy with reduced toxicity to the host. The long time development from juveniles to adults allows adequate timing for treatment of this neglected tropical disease. It is supposed that dihydroartemisinin, a safe orally administered agent, may be used for the prevention and control of human S. mansoni infections, notably in areas with reduced praziquantel sensitivity or praziquantel resistance detected.

A review of dihydroartemisinin as another gift from traditional Chinese medicine not only for malaria control but also for schistosomiasis control.

Artemisinin, also known as qinghaosu, is a sesquiterpene lactone endoperoxide extracted from the plant Artemisia annua L, an herb employed in traditional Chinese medicine. Artemisinin and its two main derivatives artemether and artesunate have been shown to be effective against both malaria and schistosomiasis, and therefore, they were described by Liu et al (Parasitol Res 110:2071-2074, 2012b) as the gifts from traditional Chinese medicine not only for malaria control but also for schistosomiasis control. However, another artemisinin derivative dihydroartemisinin (DHA) cannot be neglected. Dihydroartemisinin, a derivative of artemisinin with the C-10 lactone group replaced by hemiacetal and the active metabolite of all artemisinin compounds, was firstly identified as an antimalarial agent, and the dihydroartemisinin-piperaquine combination has been recommended as a first-line treatment of uncomplicated Plasmodium falciparum malaria by the WHO. It has been recently found that administration of dihydroartemisinin at a single dose of 300 mg/kg 2 h or 3, 5, 7, 10, 14, 18, 21, 28, or 35 days post-infection reduces total worm burdens by 1.1-64.8% and female worm burden reductions by 11.9-90.5%, and the in vivo activity of dihydroartemisinin against S. japonicum is enhanced by the use of multiple doses. However, a combination of praziquantel and dihydroartemisinin appears no more effective against S. japonicum schistosomulum than treatment with dihydroartemisinin alone. In mice experimentally infected with S. mansoni, administration with dihydroartemisinin at a single dose of 300 mg/kg on days 1, 7, 14, 21, 28, 35, 42, 49, or 56 post-infection results in total worm burden reductions of 13.8-82.1% and female worm burden reductions of 13-82.8%, and a clear-cut dose-response relationship of dihydroartemisinin against the schistosomula and adult worms of S. mansoni is observed. In addition, dihydroartemisinin was found to cause damages to the reproductive system of female S. mansoni worms, reduce the oviposition of survival worms, and inhibit the formation of granulomas around tissue-trapped eggs. More interestingly, no reduced sensitivity to dihydroartemisinin is detected in praziquantel non-susceptible S. japonicum, which provides a new option for the treatment of S. japonicum and S. mansoni infections, notably in endemic foci with praziquantel resistance or insensitivity detected. It is therefore considered that dihydroartemisinin is another gift from the traditional Chinese medicine not only for malaria control but also for schistosomiasis control.

Anion Receptor Enhanced Li Ion Transportation for High-Performance Lithium Metal Batteries.

High-potential lithium metal batteries (LMBs) are still facing many challenges, such as the growth of lithium (Li) dendrites and resultant safety hazards, low-rate capabilities, etc. To this end, electrolyte engineering is believed to be a feasible strategy and interests many researchers. In this work, a novel gel polymer electrolyte membrane, which is composed of polyethyleneimine (PEI)/poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) cross-linked membrane and electrolyte (PPCM GPE), is prepared successfully. Due to the fact that the amine groups on PEI molecular chains can provide the rich anion receptors and strongly pin the anions of electrolytes and thus confine the movement of anions, our designed PPCM GPE owns a high Li+ transference number (0.70) and finally contributes to the uniform Li+ deposition and inhibits the growth of Li dendrites. In addition, the cells with PPCM GPE as a separator behave the impressive electrochemical performances, i.e., a low overpotential and an ultralong and stable cycling performance in Li∥Li cells, a low overvoltage of about 34 mV after a stable cycling for 400 h even at a high current density of 5 mA/cm2, and, in Li∥LFP full batteries, a specific capacity of 78 mAh/g after 250 cycles at a 5 C rate. These excellent results suggest a potential application of our PPCM GPE in developing high-energy-density LMBs.

Circulating microRNAs in patients with active pulmonary tuberculosis.

Emerging evidence shows that microRNAs (miRNAs) play an important role in pathogen-host interactions. Circulating miRNAs have been repeatedly and stably detected in blood and hold promise to serve as molecular markers for diverse physiological and pathological conditions. To date, the relationship between circulating miRNAs and active pulmonary tuberculosis (TB) has not been reported. Using microarray-based expression profiling followed by real-time quantitative PCR validation, the levels of circulating miRNAs were compared between patients with active pulmonary tuberculosis and matched healthy controls. The receiver operating characteristic curve was used to evaluate the diagnostic effect of selected miRNA. Bioinformatic analysis was used to explore the potential roles of these circulating miRNAs in active pulmonary tuberculosis infection. Among 92 miRNAs significantly detected, 59 miRNAs were downregulated and 33 miRNAs were upregulated in the TB serum compared to their levels in the control serum. Interestingly, only two differentially expressed miRNAs were increased not only in the serum but also in the sputum of patients with active pulmonary tuberculosis compared to the levels for the healthy controls. Upregulated miR-29a could discriminate TB patients from healthy controls with reasonable sensitivity and specificity. A number of significantly enriched pathways regulated by these circulating miRNAs were predicted, and most of them were involved in acute-phase response, inflammatory response, and the regulation of the cytoskeleton. In all, for the first time our results revealed that a number of miRNAs were differentially expressed during active pulmonary tuberculosis infection, and circulating miR-29a has great potential to serve as a marker for the detection of active pulmonary tuberculosis infection.

LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells.

BACKGROUND AND OBJECTIVE: Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Because transforming growth factor-beta (TGF-ß) could increase survival of ovarian cancer cells in the presence of cisplatin, we conducted a preclinical study of the antitumor effects of the TGF-ß type I (TßRI) and type II (TßRII) kinase inhibitor LY2109761 in combination with cisplatin. METHODS: SKOV3, OV-90 and SKOV3(DDP) cells were treated with LY2109761, and/or cisplatin, and cell viability, apoptosis mRNA and protein expression levels were then evaluated. Furthermore, the efficacy of LY2109761 combined with cisplatin was further examined in established xenograft models. RESULTS: LY2109761 was sufficient to induce spontaneous apoptosis of ovarian cancer cells. Combination with LY2109761 significantly augmented the cytotoxicity of cisplatin in both parental and cisplatin resistant ovarian cancer cells. LY2109761 significantly increased apoptotic cell death in cisplatin-resistant cells. Combination treatment of LY2109761 and cisplatin showed antiproliferative effects and induced a greater rate of apoptosis than the sum of the single-treatment rates and promoted tumor regression in established parental and cisplatin resistant ovarian cancer xenograft models. CONCLUSIONS: Chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients.

[Preparation of polyclonal antibody and prokaryotic expression of recombinant protein RelA from Mycobacterium tuberculosis].

AIM: To prepare polyclonal antibodies against RelA protein of Mycobacterium tuberculosis. METHODS: RelA gene segment was inserted into pET-32a(+) and the recombinant protein RelA was expressed in E.coli under IPTG induction.The protein was purified and identified by SDS-PAGE and Western blot.Polyclonal antibody to RelA was got by immunizing rabbits with the protein. Quality and quantity of the antibody was identified. RESULTS: RelA gene segment was successfully inserted into pET-32a(+) and recombinant protein RelA was obtained.The polyclonal antibody to RelA had a good specificity, and the titer reached more than 1:6 400. CONCLUSION: RelA recombinant protein and rabbit anti-RelA polyclonal antibody with high specificity were obtained, which provided good tools for further studying functional characterization of RelA.