Deeply involved with dyslipidemia, cardiovascular disease has becoming the leading cause of mortality since the early twentieth century in the modern world. Whose correlation with metabolic syndrome ...(MetS), hypertension and type 2 diabetes mellitus (T2DM) has been well established. We conducted a 9-year longitudinal study to identify the association between easily measured lipid parameters, future MetS, hypertension and T2DM by gender and age distribution. Divided into three groups by age (young age: < 40, middle age: ≥ 40 and < 65 and old age: ≥ 65), 7670 participants, receiving standard medical inspection at Tri-Service General Hospital (TSGH) in Taiwan, had been enrolled in this study. Atherogenic index of plasma (AIP) was a logarithmically transformed ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C). Through multivariate regression analyses, the hazard ratio (HR) of AIP for MetS, hypertension and T2DM were illustrated. AIP revealed significant association with all the aforementioned diseases through the entire three models for both genders. Additionally, AIP revealed significant correlation which remained still after fully adjustment in MetS, hypertension, and T2DM groups for subjects aged 40-64-year-old. Nevertheless, for participants aged above 65-year-old, AIP only demonstrated significant association in MetS group. Our results explore the promising value of AIP to determine the high-risk subjects, especially meddle-aged ones, having MetS, hypertension, and T2DM in the present and the future.
Parkinson's disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present ...before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects.
The neutrophil-to-lymphocyte ratio (NLR) has received much attention in recent decades and has been a novel inflammatory marker. NLR has been applied in predicting the prognosis of malignancies, ...mortality, and chronic diseases. Additionally, hypertension, defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, a previous diagnosis of hypertension, and taking any antihypertensive drug, has been one of the most common chronic diseases in Asia and is currently the most important risk factor for cardiovascular diseases worldwide. Thus, we aimed to investigate the correlation between NLR and prevalent hypertension in the Taiwanese population. From the data of routine health checkups at the General Health Promotion Center in the Tri-Service General Hospital (TSGH), a total of 6278 participants were included. The NLR value was divided into tertiles. The Cox regression model revealed that the highest NLR group tended to be hypertensive (HR = 1.28, 95% CI 1.03-1.59) after adjustment. Individuals were also divided into age-specific, BMI-specific, or sex-specific groups; compared with the lowest NLR group, elderly individuals in the highest tertile of NLR were relatively likely to be hypertensive after covariate adjustment (HR = 1.88, 95% CI 1.19-2.96). Furthermore, a male group aged more than 60 years was reported to have a significant association with hypertension (HR = 1.84, 95% CI 1.06-3.18). However, there was no significant difference in the BMI-based stratified groups, even after adjustment. Our research revealed a significant association between the NLR and incident hypertension, especially in elderly or male Taiwanese individuals.
Transcranial focused ultrasound (tFUS) is a novel neuromodulating technique. It has been demonstrated that the neuromodulatory effects can be induced by weak ultrasound exposure levels (spatial-peak ...temporal average intensity, I
< 10 mW/cm
) in vitro. However, fewer studies have examined the use of weak tFUS to potentially induce long-lasting neuromodulatory responses in vivo. The purpose of this study was to determine the lower-bound threshold of tFUS stimulation for inducing neuromodulation in the motor cortex of rats. A total of 94 Sprague-Dawley rats were used. The sonication region aimed at the motor cortex under weak tFUS exposure (I
of 0.338-12.15 mW/cm
). The neuromodulatory effects of tFUS on the motor cortex were evaluated by the changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). In addition to histology analysis, the in vitro cell culture was used to confirm the neuromodulatory mechanisms following tFUS stimulation. In the results, the dose-dependent inhibitory effects of tFUS were found, showing increased intensities of tFUS suppressed MEPs and lasted for 30 min. Weak tFUS significantly decreased the expression of excitatory neurons and increased the expression of inhibitory GABAergic neurons. The PIEZO-1 proteins of GABAergic neurons were found to involve in the inhibitory neuromodulation. In conclusion, we show the use of weak ultrasound to induce long-lasting neuromodulatory effects and explore the potential use of weak ultrasound for future clinical neuromodulatory applications.
root extract (RCE) has been shown to possess protective activities against hypoxia both in vitro and in vivo. However, the effects of RCE on response to hypoxia in the endothelium remain unclear. In ...this study, we aimed to examine the effects of RCE in endothelial cells challenged with hypoxic exposure and to elucidate the underlying mechanisms. Human umbilical vein endothelial cells were pretreated with or without RCE and then exposed to hypoxia (1% O₂) for 24 h. Cell viability, nitric oxide (NO) production, oxidative stress markers, as well as mechanistic readouts were studied. We found that hypoxia-induced cell death, impaired NO production, and oxidative stress. These responses were significantly attenuated by RCE treatment and were associated with the activation of AMP-activated kinase and extracellular signal-regulated kinase 1/2 signaling pathways. In summary, we showed that RCE protected endothelial cells from hypoxic insult and suggested that
might be useful for the prevention of hypoxia-associated vascular dysfunction.
Colorectal cancer (CRC) is the third most common cancer worldwide with novel therapeutic developmental challenges. Polygonum barbatum has anticancer potential, but its mechanism(s) are unclear. This ...study investigates the inhibitory effect of P. barbatum on human CRC cells. Polygonum barbatum extract (PBE) and quercetin standard HPLC fingerprints were determined using analytical RP-HPLC and evaluations were completed using the human colon cancer cell line HCT-116 (KRASG13D mutation) and HT-29 (BRAF mutation) cells. Post-PBE treatment, cell viability, colony formation, migration, invasion, and apoptosis, as well as changes in the whole-transcriptome of cells were analyzed. PBE significantly reduced CRC cell growth, migration, and invasion, and the genes responsible for extracellular matrix (ECM) organization, cell motility, and cell growth were suppressed by PBE. The differentially expressed genes revealed that PBE treatment exerted a significant effect on the ECM interaction and focal adhesion pathways. Epithelial-to-mesenchymal transition markers, N-cadherin, vimentin, SLUG, and SNAIL, were shown to be regulated by PBE. These effects were associated with blockade of the Yes-associated protein and the GSK3β/β-catenin axis. PBE exerts a significant inhibitory effect on CRC cells and may be applicable in clinical trials.
Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising neuromodulation technique that delivers acoustic energy with high spatial resolution for inducing long-term potentiation ...(LTP)- or depression (LTD)-like plasticity. The variability in the primary effects of tFUS-induced plasticity could be due to different stimulation patterns, such as intermittent versus continuous, and is an aspect that requires further detailed exploration. In this study, we developed a platform to evaluate the neuromodulatory effects of intermittent and continuous tFUS on motor cortical plasticity before and after tFUS application. Three groups of rats were exposed to either intermittent, continuous, or sham tFUS. We analyzed the neuromodulatory effects on motor cortical excitability by examining changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We also investigated the effects of different stimulation patterns on excitatory and inhibitory neural biomarkers, examining c-Fos and glutamic acid decarboxylase (GAD-65) expression using immunohistochemistry staining. Additionally, we evaluated the safety of tFUS by analyzing glial fibrillary acidic protein (GFAP) expression. The current results indicated that intermittent tFUS produced a facilitation effect on motor excitability, while continuous tFUS significantly inhibited motor excitability. Furthermore, neither tFUS approach caused injury to the stimulation sites in rats. Immunohistochemistry staining revealed increased c-Fos and decreased GAD-65 expression following intermittent tFUS. Conversely, continuous tFUS downregulated c-Fos and upregulated GAD-65 expression. In conclusion, our findings demonstrate that both intermittent and continuous tFUS effectively modulate cortical excitability. The neuromodulatory effects may result from the activation or deactivation of cortical neurons following tFUS intervention. These effects are considered safe and well-tolerated, highlighting the potential for using different patterns of tFUS in future clinical neuromodulatory applications.
Acute colonic pseudoobstruction (ACPO) is a medical emergency defined as acute colonic distention without mechanical obstruction or inflammatory status. The initial treatment for ACPO includes ...conservative therapy and gastrointestinal tube decompression. Colonic endoscopic decompression is indicated in patients who fail to respond to conservative treatment. If none of the above treatments are effective, surgeries such as cecostomy must be considered. We report the case of a 77‑year‑old man with a history of Parkinson's disease who was receiving anti‑Parkinson agent therapy. The patient presented with abdominal distention for 1 week, and ACPO was diagnosed. The patient received conservative treatment after admission; however, the symptoms and imaging findings did not improve. Endoscopic decompression was unsuccessful. Subsequently, we successfully treated the patient with a novel technique by placing a decompression tube into the proximal colon under the guidance of a colonoscope.
The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments ...at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar’s test were used for group comparisons, and Kaplan–Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38–7.73 for RFS, HR = 2.35 and 95% CI = 1.17–4.71 for PFS, HR = 4.32 and 95% CI = 1.8–10.5 for OS. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue HR = 2.33, 95% CI = 1.07–5.08 for RFS, HR = 2.42 and 95% CI = 1.19–4.91 for PFS. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.
Parasitic infections may cause significant effects on behavior, learning, and memory of the host. In the brain of mice heavily infected with Angiostrongylus cantonensis, severe damage has been ...observed in the hippocampus. This component has been considered to have associations with spatial learning and memory in humans and vertebrates. This study was designed to determine the impairments in behavior, learning, and memory in BALB/c and C57BL/6 mice heavily infected with the parasite.
Each mouse was inoculated with 50 third-stage larvae of A. cantonensis. After infection, daily changes in weight and dietary consumption, worm recoveries and survival rates were determined. The forced swimming test, open field test, and Morris water maze test were employed to evaluate depression- and anxiety-like behavior as well as impairments in spatial learning and memory, respectively.
The worm recovery rate in the BALB/c mice was significantly lower than that of C57BL/6 mice from day 14 post-infection. The survival rate in infected BALB/c mice decreased to 0% by day 25 whereas those with swim-training survived three more days. On day 42, the C57BL/6 mice had a survival rate of 85.7% in the swimming group and 70% in the non-swimming group. Significant differences were found in weight between infected and non-infected BALB/c and C57BL/6 mice from day 13 and day 12, respectively with corresponding changes in their dietary consumption. Depression-like behavior was found in the infected BALB/c mice but not in C57BL/6 mice. However, anxiety-like behavior was found to occur only in C57BL/6 mice. Impaired spatial learning and memory were also found in the two strains of mice which occurred from day 14 post-infection.
Results of this study indicate that A. cantonensis causes depression, anxiety, and impairments in spatial learning and memory in heavily infected mice. Moreover, significantly higher severity was observed in the Th-2 dominant BALB/c mice.
PDF
