The Efficacy of V. odorata Extract in the Treatment of Insomnia: A Systematic Review and Meta-Analysis.

Aim: This systematic review and meta-analysis was performed to assess the effect of Viola odorata (V. odorata) extract in the treatment of insomnia. Methods: PubMed, EMBASE, and Cochrane Library databases, as well as references of related articles, were searched. Finally, four articles with five clinical trials including 224 patients were included in the analysis. Results: The obtained results indicated a greater improvement in total PSQI scores (MD,-4.67; P = 0.0002), subjective sleep quality score (MD,-0.91; P = 0.003), sleep duration score (MD,-0.77; P < 0.00001), and ISI score (MD,-6.30; P = 0.009) in the Viola extract group compared with the placebo group. However, the Viola extract group did not significantly differ in sleep latency (MD,-0.85; P = 0.08), habitual sleep efficiency (MD,-0.61; P = 0.21), sleep disturbances (MD,-0.36; P = 0.11), and daytime dysfunction (MD,-0.94; P = 0.12) from the placebo group. Conclusions: Viola extract supplement led to a greater improvement in total PSQI scores, subjective sleep quality score, sleep duration score, and ISI score compared with the placebo group of patients with chronic insomnia.

Specific structuro-metabolic pattern of thalamic subnuclei in fatal familial insomnia: A PET/MRI imaging study.

BACKGROUND: Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations. MATERIALS AND METHODS: Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel-based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features. RESULTS: The whole-brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios. CONCLUSIONS: Our study revealed specific structuro-metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.

Charge-reversal nanomedicine based on black phosphorus for the development of A Novel photothermal therapy of oral cancer.

Driven by the lifestyle habits of modern people, such as excessive smoking, drinking, and chewing betel nut and other cancer-causing foods, the incidence of oral cancer has increased sharply and has a trend of becoming younger. Given the current mainstream treatment means of surgical resection will cause serious damage to many oral organs, so that patients lose the ability to chew, speak, and so on, it is urgent to develop new oral cancer treatment methods. Based on the strong killing effect of photothermal therapy on exposed superficial tumors, we developed a pH-responsive charge reversal nanomedicine system for oral cancer which is a kind of classic superficial tumor. With excellent photothermal properties of polydopamine (PDA) modified black phosphorus nanosheets (BP NSs) as basal material, then used polyacrylamide hydrochloride-dimethylmaleic acid (PAH-DMMA) charge reversal system for further surface modification, which can be negatively charged at blood circulation, and become a positive surface charge in the tumor site weakly acidic conditions due to the breaking of dimethylmaleic amide. Therefore, the uptake of oral cancer cells was enhanced and the therapeutic effect was improved. It can be proved that this nanomedicine has excellent photothermal properties and tumor enrichment ability, as well as a good killing effect on oral cancer cells through in vitro cytotoxicity test and in vivo photothermal test, which may become a very promising new model of oral cancer treatment.

Tenuigenin protects dopaminergic neurons from inflammation via suppressing NLRP3 inflammasome activation in microglia.

BACKGROUND: Emerging evidence indicates that nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of PD. Tenuigenin, a major active component of Polygala tenuifolia, has been shown to have potential anti-inflammatory activity, but the underlying mechanisms remain obscure. METHODS: In the present study, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was established to explore the effect of tenuigenin on dopaminergic neurons in substantia nigra. We next activated NLRP3 inflammasome in both BV2 microglia cells and adult mice to investigate the mechanisms for the neuroprotective effect of tenuigenin. RESULTS: We demonstrated that treatment with tenuigenin increased striatal dopaminergic levels and improved motor impairment induced by MPTP. Also, tenuigenin significantly ameliorated the degeneration of dopaminergic neurons and inhibited NLRP3 inflammasome activation in substantia nigra of MPTP mouse model. We further found that tenuigenin reduced intracellular reactive oxygen species (ROS) production and suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1ß secretion in BV2 microglia cells. These data indicate that tenuigenin inhibits the activation of NLRP3 inflammasome via downregulating ROS. Correspondingly, in vivo data showed that tenuigenin attenuates microglia activation induced by lipopolysaccharide (LPS) in substantia nigra via suppressing NLRP3 inflammasome. CONCLUSIONS: Our findings reveal that tenuigenin protects dopaminergic neurons from inflammation partly through inhibition of NLRP3 inflammasome activation in microglia, and suggest the promising clinical use of tenuigenin for PD therapy.

Experimental study on ablation of leiomyoma by combination high-intensity focused ultrasound and iodized oil in vitro.

AIM: The aim of the current study was to investigate whether iodized oil (IO) enhances high-intensity focused ultrasound (HIFU) ablation of uterine leiomyoma and to determine the features of hyperechoic changes in the target region. METHODS: Forty samples of uterine leiomyoma were randomly divided into an experimental group and a control group. In the experimental group, the leiomyoma was ablated by HIFU 30 min after 1 mL of iodized oil had been injected into the center of the myoma. The hyperechoic values and areas in the target region were observed by B-modal ultrasound after HIFU ablation. The samples were cut successively into slices and stained by triphenyltetrazolium chloride (TTC) solution within 1 h after HIFU ablation. The diameters of TTC-non-stained areas were measured and tissues in the borderline of the TTC-stained and -non-stained areas were observed pathologically. All procedures in the control group were the same as those in the experimental group except IO was replaced by physiological saline. RESULTS: The hyperechoic value in the target region in the experimental group was higher than that in the control group 4 min after HIFU ablation (P < 0.05). Hyperechoic areas in the target region as well as TTC-non-stained volumes in the experimental group were greater than those in the control group (P < 0.05). Routine pathologic observation showed that coagulation necrosis of leiomyoma occurred in the target region in both groups. CONCLUSION: IO causes coagulation necrosis, enlarges tissue damage, and postpones the attenuation of hyperechoic changes in the target region when HIFU ablation is carried out for leiomyoma in vitro.

Characteristics of blood chemistry, hematology, and lymphocyte subsets in pregnant rhesus monkeys.

The present study was designed to characterize the blood chemistry, hematology, and lymphocyte subsets in pregnant rhesus monkeys and provide baseline parameters for future studies of reproductive and developmental toxicity and developmental immunotoxicity. Harem-mating was used in 96 female and 16 male rhesus monkeys. Pregnancy was confirmed on gestation day (GD)18 by ultrasound. The blood samples of rhesus monkeys were collected at various times (20 days before pregnancy and GD20, 100 and 150). The analyses of blood chemistry, hematology, and lymphocyte subsets were performed. Compared with 20 days before pregnancy, Significant decreases (P < 0.05) were observed in HCT and RBC on GD20, GD150 and in HGB on GD150, Significant increases in NEUT and decreases in LYMPH on GD20 were observed. Significant decreases in ALB from GD20 to GD150 were observed, significant decreases in TP was observed on GD100. Significant increases in mean GLU were observed on GD20 and GD150 during pregnancy. Significant decreases (P < 0.05) in CD20(+) subsets on GD100, GD150 and CD4(+)/CD8(+)ratio on GD150 were observed, The significant changes of MCV, MCHC, RDW-SD, MCV, MONO, ALT, AST, GLB, ALP, TBIL, DBIL, IBIL, GGT, CR-S, URIC, TC, TG and CK were observed during the pregnant period, but no biologic change were observed, There were no significant changes in MCH, RDW-CV, MPV, BUN, CD3(+), CD4(+) and CD8(+) during pregnancy. These data provide a database for preclinical study in rhesus monkeys. Physiological anemia, hyperglycemia, and immune suppression may occur in pregnant rhesus monkey which is similar to that found in human, and it is essential to distinguish the physiological changes from the pharmacological effects in reproductive and developmental toxicity and developmental immunotoxicity studies of pharmaceuticals.

Tenuigenin attenuates α-synuclein-induced cytotoxicity by down-regulating polo-like kinase 3.

BACKGROUND AND AIMS: Tenuigenin (Ten) is a Chinese herbal extract with antioxidative and antiinflammatory effects on toxin-induced cell models of Parkinson's disease (PD); however, its effects on α-synuclein toxicity-based PD models remain unknown. α-synuclein hyperphosphorylation is a key event in PD pathogenesis and potential target of therapeutic interventions. We tested whether Ten alleviates α-synuclein-induced cytotoxicity via reducing kinases that phosphorylate α-synuclein. METHODS: SH-SY5Y cells transiently transfected with wild-type or A53T mutant α-synuclein were used to evaluate the effect of Ten on the levels of α-synuclein phosphorylation-related kinases. Cells treated with 10 µM Ten for 24 h were measured for viability (proliferation and apoptosis assays) and cellular proteins harvested and fractioned. The levels of total and phosphorylated α-synuclein and five associated kinases (polo-like kinase [PLK] 1-3, casein kinase [CK] 1-2) were evaluated by Western blotting. RESULTS: Overexpression of either wild-type or A53T mutant α-synuclein decreased cell viability and increased α-synuclein phosphorylation. Ten treatment-protected cells from this α-synuclein-induced toxicity and dramatically reduced α-synuclein phosphorylation and PLK3 (but not other kinase) levels. CONCLUSION: In α-synuclein cell model of PD, Ten is effective in attenuating α-synuclein-induced toxicity and α-synuclein phosphorylation probably via targeting PLK3, suggesting it could be an efficient therapeutic drug to treat α-synuclein-related neurodegeneration.

Neuroprotective effects of tenuigenin in a SH-SY5Y cell model with 6-OHDA-induced injury.

Tenuigenin, an active component of Polygala tenuifolia root extracts, has been shown to provide antioxidative and anti-aging effects in Alzheimer's disease, as well as to promote proliferation and differentiation of neural progenitor cells. However, the effects of tenuigenin on Parkinson's disease remain unclear. In the present study, SH-SY5Y cells were utilized to determine the effects of tenuigenin on 6-hydroxydopamine (6-OHDA)-induced injury. Results showed that 1.0 × 10⁻¹-10 µM tenuigenin significantly promoted cell viability and reduced cell death. In addition, tenuigenin protected mitochondrial membrane potential (MMP) against 6-OHDA damage and significantly increased glutathione and superoxide dismutase expression. At the mRNA level, tenuigenin resulted in down-regulation of caspase-3, but up-regulation of tyrosine hydroxylase expression in 6-OHDA damaged cells. These results suggested that tenuigenin provides neuroprotection to dopaminergic neurons from 6-OHDA-induced damage. The neuroprotective mechanisms might involve antioxidative effects, maintenance of mitochondrial function, and regulation of caspase-3 and tyrosine hydroxylase expression and activity. Tenuigenin could provide a novel antioxidative strategy for Parkinson's disease.