Icariside II (ICA II) is used in erectile dysfunction treatment. Adipose tissue-derived stem cells (ADSCs) are efficient at improving erectile function. This study aimed to explore the action ...mechanism of ADSCs in improving erectile function. ADSCs were isolated from the adipose tissues of rats. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. The expressions of mRNA and protein were determined separately through qRT-PCR and western blot. The endogenous expressions of related genes were regulated using recombinant plasmids and cell transfection. A Dual-Luciferase Reporter Assay was performed to determine the interaction between miR-34a and STAT3. Rat models with bilateral cavernous nerve injuries (BCNIs) were used to assess erectile function through the detection of mean arterial pressure (MAP) and intracavernosal pressure (ICP). ICA II promoted ADSCs' proliferation and differentiation to Schwann cells (SCs) through the inhibition of miR-34a. Suppressed miR-34a promoted the differentiation of ADSCs to SCs by upregulating STAT3. ICA II promoted the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway. The combination of ICA II and ADSCs preserved the erectile function of the BCNI model rats. ADSCs treated with ICA II markedly preserved the erectile function of the BCNI model rats, which was reversed through miR-34a overexpression. ICA II promotes the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway, contributing to erectile function preservation after the occurrence of a cavernous nerve injury.
Sleep disorders other than sleep apnea (non-apnea sleep disorder, NSD), esp. insomnia and excessive daytime sleepiness, has been reported to induce higher risk of cognitive decline and dementia in ...previous longitudinal follow-up studies. However, large-scale nationwide populationbased study may further confirm the association between NSD and dementia.
It was a nationwide population-based retrospective study. We used data from Taiwan's National Health Insurance Research Database (NHIRD) between January 2000 and December 2011. The NSD cohort comprised 92,079 patients aged over 20 years with no preexisting dementia. The comparison cohort was propensity-score matched 1:1 with 92079 controls. Incident dementia cases were identified to the end of 2011. The NSD cohort to non-NSD cohort adjusted hazard ratios (aHRs) of dementia were assessed using multivariable Cox proportional hazards regression analysis.
Incidence of dementia was 4.19 and 2.95 per 1,000 person-years in the NSD and non-NSD cohorts, respectively, with an aHR of 1.46 (95% CI=1.38-1.54; p<0.0001). Risk of dementia was higher in both gender and whole age subgroup, with slightly higher in men (aHR: 1.48, 95% CI=1.35-1.62, p<0.0001) and in the younger population (aHR: 2.79, 95% CI=1.63-4.78, p<0.0001). Dementia was most likely to occur in the first year of follow-up (aHR: 1.73, 95% CI=1.49-2.02; p<0.0001), but dementia risk remained high 5 years after NSD diagnosis compared to controls (aHR: 1.44, 95% CI=1.32-1.57; p<0.0001).
NSD may be an early indicator of decline in cognitive functioning and onset of dementia in the short-term period. It also carries a higher risk for dementia in the long run. Patients with NSD should require close monitoring for cognitive decline.
Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric ...oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker has been proven to reduce early brain injury after SAH. This study investigated the effect of memantine on attenuation of vasospasm and restoring eNOS functionality. Male Sprague-Dawley rats weighing 350-450 g were randomly divided into three weight-matched groups, sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the severity of vasospasm and the expression of eNOS. Memantine effectively ameliorated cerebral vasospasm by restoring eNOS functionality. Memantine can prevent vasospasm in experimental SAH. Treatment strategies may help combat SAH-induced vasospasm in the future.
Stroke is a major cause of disability in the elderly and considerably increases the risk of dementia, which is another important source of disability. This population-based study aimed to examine the ...risk of dementia in patients with stroke compared with non-stroke cases with similar comorbidities.
Using the Taiwan National Health Insurance databank covering the period 2001-2007, this retrospective cohort study evaluated the risk of dementia in 10,884 patients with first stroke who had no history of dementia. In this study, we performed a 1:5 case-control matched analysis, in which cases were matched to controls based on their estimated propensity scores, which were estimated with demographics and associated risk factors. This approach reduced selection bias. Cox proportional hazards regression analysis was then used to estimate the risk of dementia in stroke patients.
During the 5-year follow-up period, 1,487 (13.74%) stroke and 1,402 (2.59%) non-stroke patients suffered dementia. Stroke was independently associated with a 6.09 (95% confidence interval CI, 5.66 to 6.55) times greater risk of dementia 5 years after stroke. Older age was associated with a higher incidence of dementia after stroke. Each stroke type had different impacts on the occurrence of dementia. The hazard ratio of dementia among hemorrhagic stroke patients was much higher than those of ischemic stroke and controls.
The findings of this study suggest that stroke confers an increased risk of dementia, especially in the elderly and in patients with hemorrhagic stroke. We advocate the need for close observation and enhanced health education programs to benefit patients with stroke.
Abstract
TAR DNA-binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar ...degeneration-TDP and amyotrophic lateral sclerosis. We found that transthyretin accumulates with TDP-43 cytoplasmic inclusions in frontal temporal lobar degeneration-TDP human patients and transgenic mice, in which transthyretin exhibits dramatic expression decline in elderly mice. The upregulation of transthyretin expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, in which transthyretin induces autophagy upregulation via ATF4. Of interest, transthyretin upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of transthyretin in frontal temporal lobar degeneration-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioural deficits. Thus, transthyretin conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that transthyretin is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy.
Chu et al. report that transthyretin (TTR) co-aggregates with TDP-43 in the brains of FTLD-TDP patients and transgenic mice. TTR potentiates autophagy activity via ATF4 and facilitates the targeting of soluble TDP-43 aggregates into autophagosomes for degradation.
Aim. Autoimmune rheumatic diseases (ARD) are characterized by systemic inflammation and may affect multiple organs and cause vascular events such as ischemic stroke and acute myocardial infarction. ...However, the association between ARD and increased risk of dementia is uncertain. This is a retrospective cohort study to investigate and compare the risk of dementia between patients clinically diagnosed with ARD and non-ARD patients during a 5-year follow-up period. Methods. Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID2000). We included 1221 patients receiving ambulatory or hospitalization care and 6105 non-ARD patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied for 5 years to identify the subsequent manifestation of dementia. The data obtained were analyzed by Cox proportional hazard regression. Results. During the 5-year follow-up period, 30 ARD (2.48%) and 141 non-ARD patients (2.31%) developed dementia. During the 5-year follow-up period, there were no significant differences in the risks of any type of dementia (adjusted hazard ratio (HR), 1.18; 95% CI, 0.79–1.76) in the ARD group after adjusting for demographics and comorbidities. Conclusions. Within the 5-year period, patients with and without ARD were found to have similar risks of developing dementia.
The relationship between traumatic brain injury (TBI) and the risk of dementia remains controversial. This population based study was designed to estimate and compare the risk of dementia in TBI and ...non-TBI individuals during the 5 year period after TBI.
This study was a retrospective cohort study. Data were obtained from the Longitudinal Health Insurance Database 2000. We included 44,925 patients receiving ambulatory or hospital care and 224,625 non-TBI patients; patients were matched for sex, age and year of index use of healthcare. Patients <15 years of age and those admitted to the intensive care unit were excluded. Each individual was studied for 5 years to identify the subsequent development of dementia. Data were analysed by Cox proportional hazard regression.
During the 5 year follow-up period, 1196 TBI (2.66%) and 224,625 non-TBI patients (1.53%) patients developed dementia. During the 5 year follow-up period, TBI was independently associated with a 1.68 (range 1.57-1.80) times greater risk of dementia after adjusting for sociodemographic characteristics and selected comorbidities.
The findings of this study suggest an increased risk of dementia among individuals with TBI. We suggest the need for more intensive medical monitoring and health education in individuals with TBI.
Recent studies reported granulocyte colony-stimulating factor (G-CSF) treatment can improve the cognitive function of Alzheimer’s disease (AD) mice, and the mobilized hematopoietic stem cells (HSCs) ...or bone marrow mesenchymal stem cells (BM-MSCs) are proposed to be involved in this recovery effect. However, the exact role of mobilized HSC/BM-MSC in G-CSF-based therapeutic effects is still unknown. Here, we report that C-X-C chemokine receptor type 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) chemotaxis was a key mediator in G-CSF-based therapeutic effects, which was involved in the recruitment of repair-competent cells. Furthermore, we found both mobilized HSCs and BM-MSCs were able to infiltrate into the brain, but only BM-MSCs replenished the neural lineage cells and contributed to neurogenesis in the brains of AD mice. Together, our data show that mobilized BM-MSCs are involved in the replenishment of neural lineages following G-CSF treatment via CXCR4/SDF-1 chemotaxis and further support the potential use of BM-MSCs for further autogenically therapeutic applications.
Primary Intracranial Melanoma Lee, Po-Hsuan; Wang, Liang Chao; Lee, E-Jian
Journal of cancer research and practice,
March 2017, Letnik:
4, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract Primary intracranial malignant melanomas are rarely reported tumors of the central nervous system that are highly malignant with a poor prognosis, accounting for 0.1% of intracranial ...neoplasms. Given the location of the tumor, preoperative diagnosis by imaging study is difficult. Typically, mainstream therapy involves total excision of the tumor followed by radiation therapy. We present a case of primary intracranial melanoma arising from convexity of the left frontal lobe in a 49-year-old male who presented with headache and progressive mentality change for one month. After total tumor excision and whole brain radiation therapy, the patient has experienced tumor-free survival extending through 47 months of follow-up. Herein we have reported the patient’s MRI findings, pathological examination, treatment and outcome.
Ischemic stroke is the leading cause of disability and death worldwide. An effective therapeutic approach is urgently needed. Stroke-induced angiogenesis and neurogenesis are essential mechanisms in ...the long-term repair. Extracellular matrix proteins are also involved in tissue self-repair. Recently, a PHSRN (Pro-His-Ser-Arg-Asn) peptide from the fibronectin synergistic motif that can promote wound healing in epithelia and induce endothelial proliferation and cancer cell migration was identified. The therapeutic potential of this peptide in stroke is unknown. Here, we examined the potential of PHSRN in stroke therapy using an ischemic rat model of middle cerebral artery occlusion (MCAO). PHSRN reduced the infarct volume in MCAO rats, improved neurological function, and alleviated motor function impairment. PHSRN targeted the damaged brain region and distributed to endothelial cells after intraperitoneal injection. PHSRN significantly promoted angiogenesis and vascular endothelial growth factor secretion through activation of integrin α5β1 and its downstream intracellular signals, e.g., focal adhesion kinase, Ras, cRaf, and extracellular-signal-regulated kinase. PHSRN treatment also stimulated neurogenesis in MCAO rats, and maintained neuronal survival and neuronal morphologic complexity via induction of VEGF secretion. Together, these results provide insights into the role of integrin α5β1 following ischemia and support the feasibility of using PHSRN peptide in stroke therapy.
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