Intravascular laser irradiation of blood as novel migraine treatment: an observational study.

BACKGROUND: Migraine is one of four major chronic diseases that cause disability. Decreases in regional cerebral blood flow (rCBF) occur during migraine attacks. Laser therapy is extensively employed in treating other vascular diseases; nevertheless, its effectiveness in migraine management remains largely unknown. Therefore, we evaluated the effect of low-level intravascular laser irradiation of blood (ILIB) therapy in patients with migraine. METHODS: We performed an observational case-control study in 24 patients suffering from migraine. Patients were divided into an ILIB treatment group and a traditional rehabilitation group. This study performed clinical assessments and single-photon emission computed tomography (SPECT) prior to and after the treatment and 1 month later. Changes in rCBF-SPECT between groups and between timepoints were compared to clinical outcomes. RESULTS: Nine patients undergoing rehabilitation and fifteen patients undergoing ILIB were studied from baseline to 1 month follow-up. The ILIB group, visual analog scale for pain (P = 0.001), Montreal Cognitive Assessment (P = 0.003), and Athens Insomnia Scale (P < 0.001) symptom scores significantly improved after treatment. SPECT imaging showed a 1.27 ± 0.27 fold increase in rCBF after ILIB treatment, and no significant differences in the rehabilitation group. CONCLUSIONS: Low-level ILIB therapy is associated with better clinical and vascular outcomes, and may be a feasible treatment option for migraine. Although our sample size was small, our data provide a starting point for migraine laser therapy research.

Investigating the effects of Ceylon cinnamon water extract on HepG2 cells for Type 2 diabetes therapy.

Cinnamon and its extracts have been used as herbal remedies for many ailments, including for reducing insulin resistance and diabetes complications. Type 2 diabetes mellitus (T2DM) is a rapidly growing health concern around the world. Although many drugs are available for T2DM treatment, side effects and costs can be considerable, and there is increasing interest in natural products for managing chronic health conditions. Cinnamon may decrease the expression of genes associated with T2DM risk. The purpose of this study was to evaluate the effects of cinnamon water extract (CWE) compared with metformin on T2DM-related gene expression. HepG2 human hepatoma cells, widely used in drug metabolism and hepatotoxicity studies, were treated with different concentrations of metformin or CWE for 24 or 48 h. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and glucose uptake was compared in untreated and CWE- or metformin-treated cells under high-glucose conditions. Finally, total RNA was extracted and analyzed by RNA sequencing (RNA-seq), and bioinformatics analyses were performed to compare the transcriptional effects of CWE and metformin. We found cell viability was better in cells treated with CWE than in metformin-treated cells, demonstrating that CWE was not toxic at tested doses. CWE significantly increased glucose uptake in HepG2 cells, to the same degree as metformin (1.4-fold). RNA-seq data revealed CWE and metformin both induced significantly increased (1.3- to 1.4-fold) glucose uptake gene expression compared with untreated controls. Transcriptional differences between CWE and metformin were not significant. The effects of 0.125 mg mL-1 CWE on gene expression were comparable to 1.5 mg mL-1 (9.5 mM) metformin. In addition, gene expression at 0.125 mg mL-1 CWE was comparable to 1.5 mg mL-1 (9.5 mM) metformin. Our results reveal that CWE's effects on cell viability, glucose uptake, and gene expression in HepG2 cells are comparable to those of metformin, suggesting CWE may be an effective dietary supplement for mitigating T2DM-related metabolic dysfunction.

Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR-92a.

Lung adenocarcinoma (LUAD) is one of the most prevalent malignancies. However, its mechanism and therapeutic strategy remain to be clarified. Mangiferin is a flavonoid derived from the leaves of mango trees of the lacquer family that has many pharmacological and physiological effects. This research aimed to elucidate the biological effect of mangiferin in LUAD cell lines and clarify the in vitro mechanism of mangiferin. Mangiferin was shown to significantly restrain the proliferation of LUAD cells (A549, H1299, and H2030 cells) in a dose- and time-dependent manner. Furthermore, mangiferin was capable of stimulating apoptosis, and more cells were blocked in G1 and S phase in the mangiferin-treated cells than in those not treated with mangiferin. Microarrays and micro-RNA sequencing data suggested that there is a higher level of miR-27b and miR-92a in LUAD tissues than in non-LUAD tissues. Additional experiments indicated that mangiferin may be related to the downregulated levels of miR-92a and miR-27b. In conclusion, mangiferin likely regulates proliferation and apoptosis in LUAD cells by reducing the expression levels of miR-92a and miR-27b.

Incidence and survival impact of pulmonary arterial hypertension among patients with systemic lupus erythematosus: a nationwide cohort study.

BACKGROUND: No population-based study has investigated the cumulative incidence of pulmonary arterial hypertension (PAH) in patients with newly diagnosed systemic lupus erythematosus (SLE) or the survival impact of PAH in this population. METHOD: We used a nationwide database in Taiwan and enrolled incident SLE patients between January 1, 2000, and December 31, 2013. The cumulative incidence of PAH in the SLE patients and the survival of these patients were estimated by the Kaplan-Meier method. Potential predictors of the development of PAH were determined using a Cox proportional hazards regression model. RESULTS: Of 15,783 SLE patients, 336 (2.13%) developed PAH. The average interval from SLE diagnosis to PAH diagnosis was 3.66 years (standard deviation [SD] 3.36, range 0.1 to 13.0 years). Seventy percent of the patients developed PAH within 5 years after SLE onset. The 3- and 5-year cumulative incidence of PAH were 1.2% and 1.8%, respectively. Systemic hypertension was an independent predictor of PAH occurrence among the SLE patients (adjusted hazard ratio 2.27, 95% confidence interval 1.59-2.97). The 1-, 3-, and 5-year survival rates of SLE patients following the diagnosis of PAH were 87.7%, 76.8%, and 70.1%, respectively. CONCLUSIONS: PAH is a rare complication of SLE and the majority of PAH cases occur within the first 5 years following SLE diagnosis. Systemic hypertension may be a risk factor for PAH development in the SLE population. The overall 5-year survival rate after PAH diagnosis was 70.1%.

The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA-10 Mouse Leydig Tumor Cells.

Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS). We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR) subtype agonists were further used to treat MA-10 cells, showing that A(1), A( 2A ), A( 2B ), and A(3), AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

Cordycepin Induced MA-10 Mouse Leydig Tumor Cell Apoptosis through Caspase-9 Pathway.

In the present study, the apoptotic effect of cordycepin on MA-10 cells, a mouse Leydig tumor cell line, was investigated. Results demonstrated that the number of rounding-up cell increased by cordycepin (10 µM to 5 mM for 24 h), and cells with plasma membrane blebbing could be observed by 100 µM cordycepin. In viability test, MA-10 cell surviving rate significantly decreased as the dosage (10 µM to 5 mM) and duration (3-24 h) of cordycepin treatment increased (P < 0.05). Cordycepin at 100 µM and 1 mM for 24 h treatment induced significant DNA fragmentation (P < 0.05). In addition, the percentage of G1 and G2/M phase cell significantly declined by cordycepin (100 µM and 1 mM) for 24 h treatment, while the percentages of subG1 phase cell increased by 100 µM and/or 1 mM cordycepin in 6, 12 and 24 h treatments (P < 0.05), respectively, which highly suggested that cordycepin induced MA-10 cell apoptosis. In mechanism study with the treatments of caspases, c-Jun NH(2) terminal kinase (JNK) or reactive oxygen species (ROS) inhibitors plus cordycepin for 24 h, only caspases inhibitor suppressed subG1 phase in MA-10 cells. Moreover, western blotting results showed that cordycepin induced caspase-9, -3 and -7 protein expressions, but not caspase-8, in time- and dose-dependent manners. In conclusion, cordycepin induced apoptosis in MA-10 mouse Leydig tumor cells through a caspase-9 and -3 and -7 dependent pathway.

Zingiber officinale (ginger) compounds have tetracycline-resistance modifying effects against clinical extensively drug-resistant Acinetobacter baumannii.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) is a growing and serious nosocomial infection worldwide, such that developing new agents against it is critical. The antimicrobial activities of the rhizomes from Zingiber officinale, known as ginger, have not been proven in clinical bacterial isolates with extensive drug-resistance. This study aimed to investigate the effects of four known components of ginger, [6]-dehydrogingerdione, [10]-gingerol, [6]-shogaol and [6]-gingerol, against clinical XDRAB. All these compounds showed antibacterial effects against XDRAB. Combined with tetracycline, they showed good resistance modifying effects to modulate tetracycline resistance. Using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method, these four ginger compounds demonstrated antioxidant properties, which were inhibited by MnO2, an oxidant without antibacterial effects. After the antioxidant property was blocked, their antimicrobial effects were abolished significantly. These results indicate that ginger compounds have antioxidant effects that partially contribute to their antimicrobial activity and are candidates for use in the treatment of infections with XDRAB.

BOLD response to direct thalamic stimulation reveals a functional connection between the medial thalamus and the anterior cingulate cortex in the rat.

Recent functional neuroimaging studies in humans and rodents have shown that the anterior cingulate cortex (ACC) is activated by painful stimuli, and plays an important role in the affective aspect of pain sensation. The aim of the present study was to develop a suitable stimulation method for direct activation of the brain in fMRI studies and to investigate the functional connectivity in the thalamo-cingulate pathway. In the first part of the study, tungsten, stainless steel, or glass-coated carbon fiber microelectrodes were implanted in the left medial thalamus (MT) of anesthetized rats, and T2*-weighted gradient-echo (GE) images were obtained in the sagittal plane on a 4.7 T system (Biospec BMT 47/40). Only the images obtained with the carbon fiber electrode were acceptable without a reduction of the signal-to-noise ratio (SNR) and image distortion. In the second part of the study, a series of two-slice GE images were acquired during electrical stimulation of the MT with the use of a carbon fiber electrode. A cross-correlation analysis showed that the signal intensities of activated areas in the ipsilateral ACC were significantly increased by about 4.5% during MT stimulation. Functional activation, as assessed by the distribution of c-Fos immunoreactivity, showed strong c-Fos expression in neurons in the ipsilateral ACC. The present study shows that glass-coated carbon fiber electrodes are suitable for fMRI studies and can be used to investigate functional thalamocortical activation.

A method for direct thalamic stimulation in fMRI studies using a glass-coated carbon fiber electrode.

Recent fMRI studies are of interest in exploring long-range interactions between different brain structures and the functional activation of specific brain regions by known neuroanatomical pathways. One of the experimental approaches requires the invasive implantation of an intracranial electrode to excite specific brain structures. In the present report, we describe a procedure for the production of a glass-coated carbon fiber electrode and the use of this electrode for direct activation of the brain in fMRI studies. The glass-coated carbon fiber microelectrode was implanted in the medial thalamus of anaesthetized rats and T2*-weighted gradient echo images in the sagittal plane obtained on a 4.7 T system (Biospec BMT 47/40) during electrical stimulation of the medial thalamus. The image quality obtained using this electrode was acceptable without reduction of the signal-to-noise ratio and image distortion. Cross-correlation analysis showed that the signal intensities of activated areas in the ipsilateral anterior cingulate cortex were significantly increased by about 4-5% during medial thalamus stimulation. The present study shows that glass-coated carbon fiber electrodes are suitable for fMRI studies and can be used to investigate functional thalamocingulate activation.

The effect of Gu-Sui-Bu (Drynaria fortunei J. Sm) immobilized modified calcium hydrogenphosphate on bone cell activities.

In our previous study, we have validated the efficacy and the safety of Gu-Sui-Bu [Drynaria fortunei (Kunze) J. Sm.] by the bone cells culture. However, a satisfactory delivery system for Gu-Sui-Bu must be developed before it can be used in clinical medicine. In this study, we try to use modified calcium hydrogenphosphate (MCHP) bioceramic as a carrier to transport Gu-Sui-Bu into the bone cell culture system. Toward this goal, we evaluated the effect of a Gu-Sui-Bu-immobilized modified calcium hydrogenphosphate (GI-MCHP) on the bone cells activities. THE CHINESE MEDICINE: Gu-Sui-Bu [Drynaria fortunei (kunze) J. Sm] was extracted and then immobilized on the surface of MCHP. The rat osteoblasts-osteoclasts co-culture system was used as the experimental model. After the cells grew to 80% confluence, different sizes of GI-MCHP particles were tested. The mitochondria activity of the bone cells after exposure was determined by colorimetric assay. Biochemical markers such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and prostaglandin E(2) titer were analyzed to evaluate the bone cells activities. Histomorphometric study of osteoclasts activities and the phenotype expression of osteoblasts were also evaluated. There is no detectable titer of LDH secretion into the medium and no significant change in the intracellular ALP content. The ALP titer in the culture medium did increase significantly at 3 days' culture, while there is a significant decrease in the intracellular ACP content and significant increase in the ACP titer in the medium. The concentrations of PGE(2) in tested medium are always significantly higher than that of control medium during the 7 days' culture. At the end of 7 days' culture, the PGE(2) concentrations in the tested medium were still 4.74 times that of the control medium. After GI-MCHP treatment on bone cells, the size of the osteoclasts seems decreased and their cell integrity seems lost, while the osteoblasts phenotype expression was relatively preserved. From this study, we demonstrated that Gu-Sui-Bu [Drynaria fortunei (Kunze) J. Sm.] immobilized MCHP has well preserved the potential beneficial effects of Gu-Sui-Bu on the bone cells culture.

The effect of Gu-Sui-Bu (Drynaria fortunei J. Sm) on bone cell activities.

In the traditional Chinese medicine, Gu-Sui-Bu [Drynaria fortunei (kunze) J. Sm] has been reported as a good enhancer for bone healing. In this experiment, we investigate the biochemical effects of this traditional Chinese medicine on the bone cells culture. Different concentrations of crude extract of Gu-Sui-Bu were added to rat bone cells culture. The mitochondria activity of the bone cells after exposure was determined by colorimetric assay. Biochemical markers such as alkaline phosphatase (ALP), acid phosphatase (ACP) titer, prostaglandin E2 (PGE2) titer and the expression of both osteopontin and osteonectin mRNA were evaluated. The effect on the osteoclasts differentiation was evaluated by tartrate-resistant acid phosphatase (TRAP) stain. The most effective concentration of Gu-Sui-Bu on bone cells was 1 mg/ml. The addition of 1 mg/ml Gu-Sui-Bu to bone cells culture for 7 days can statistically increase the intracellular ALP amount; while the ACP and PGE2 amount in culture medium were significantly increased. In Northern blot analysis, the expression of both osteopontin and osteonectin mRNA were down-regulated after adding Gu-Sui-Bu into bone cells culture. The formation of multi-nucleated osteoclasts was more active than that of the control group, but no giant osteoclasts formation was observed. In this study, we demonstrated that Gu-Sui-Bu has potential effects on the bone cells culture. One of the major effects of Gu-Sui-Bu on the bone cells is probably mediated by its effect on the osteclasts activities. Continued and advanced study on the alterations in gene expression of bone cells by Chinese medicines will provide a basis for understanding the observed bone cell responses to various pharmacological interventions.