- Prion Protein PRNP: A New Player in Innate Immunity? The Aβ Connection. [Journal Article]
- JAJ Alzheimers Dis Rep 2017 Dec 16; 1(1):263-275
- The prion protein PRNP has been centrally implicated in the transmissible spongiform encephalopathies (TSEs), but its normal physiological role remains obscure. We highlight emerging evidence that PR…
The prion protein PRNP has been centrally implicated in the transmissible spongiform encephalopathies (TSEs), but its normal physiological role remains obscure. We highlight emerging evidence that PRNP displays antimicrobial activity, inhibiting the replication of multiple viruses, and also interacts directly with Alzheimer's disease (AD) amyloid-β (Aβ) peptide whose own antimicrobial role is now increasingly secure. PRNP and Aβ share share membrane-penetrating, nucleic acid binding, and antiviral properties with classical antimicrobial peptides such as LL-37. We discuss findings that binding of abnormal nucleic acids to PRNP leads to oligomerization of the protein, and suggest that this may be an entrapment and sequestration process that contributes to its antimicrobial activity. Some antimicrobial peptides are known to be exploited by infectious agents, and we cover evidence that PRNP is usurped by herpes simplex virus (HSV-1) that has evolved a virus-encoded 'anti-PRNP'.unction. These findings suggest that PRNP, like LL-37 and Aβ, is likely to be a component of the innate immune system, with implications for the pathoetiology of both AD and TSE.
- Calcitonin receptor increases invasion of prostate cancer cells by recruiting zonula occludens-1 and promoting PKA-mediated TJ disassembly. [Journal Article]
- CSCell Signal 2017; 36:1-13
- Almost all primary prostate cancers (PCs) and PC cell lines express calcitonin (CT) and/or its receptor (CTR), and their co-expression positively correlates with their invasiveness. Activation of the…
Almost all primary prostate cancers (PCs) and PC cell lines express calcitonin (CT) and/or its receptor (CTR), and their co-expression positively correlates with their invasiveness. Activation of the CT-CTR axis in non-invasive LNCaP cells induces an invasive phenotype. In contrast, silencing of CT/CTR expression in highly metastatic PC-3M cells markedly reduces their tumorigenicity and abolishes their ability to form distant metastases in nude mice. Our recent studies suggest that CTR interacts with zonula occludens 1 (ZO-1) through PDZ interaction to destabilize tight junctions and increase invasion of PC cells. Our results show that CTR activates AKAP2-anchored cAMP-dependent protein kinase A, which then phosphorylates tight junction proteins ZO-1 and claudin 3. Moreover, PKA-mediated phosphorylation of tight unction proteins required CTR-ZO-1 interaction, suggesting that the interaction may bring CTR-activated PKA in close proximity of tight junction proteins. Furthermore, inhibition of PKA activity attenuated CT-induced loss of TJ functionality and invasion, suggesting that the phosphorylation of TJ proteins is responsible for TJ disassembly. Finally, we show that the prevention of CTR-ZO-1 interaction abolishes CT-induced invasion, and can serve as a novel therapeutic tool to treat aggressive prostate cancers. In brief, the present study identifies the significance of CTR-ZO-1 interaction in progression of prostate cancer to its metastatic form.
- The effects of mirror therapy with tasks on upper extremity function and self-care in stroke patients. [Journal Article]
- JPJ Phys Ther Sci 2015; 27(5):1499-501
- [Purpose] The purpose of this study was to determine the effects of mirror therapy with tasks on upper extremity unction and self-care in stroke patients. [Subjects] Thirty participants were randomly…
[Purpose] The purpose of this study was to determine the effects of mirror therapy with tasks on upper extremity unction and self-care in stroke patients. [Subjects] Thirty participants were randomly assigned to either an experimental group (n=15) or a control group (n=15). [Methods] Subjects in the experimental group received mirror therapy with tasks, and those in the control group received a sham therapy; both therapies were administered, five times per week for six weeks. The main outcome measures were the Manual Function Test for the paralyzed upper limb and the Functional Independence Measure for self-care performance. [Results] The experimental group had more significant gains in change scores compared with the control group after the intervention. [Conclusion] We consider mirror therapy with tasks to be an effective form of intervention for upper extremity function and self-care in stroke patients.
- Serum 25-Hydroxyvitamin D, Plasma Klotho, and Lower-Extremity Physical Performance Among Older Adults: Findings From the InCHIANTI Study. [Journal Article]
- JGJ Gerontol A Biol Sci Med Sci 2015; 70(9):1156-62
- CONCLUSIONS: Plasma klotho and 25(OH)D both positively related to lower-extremity physical performance. However, the findings did not support the hypothesis that klotho mediates the relation of 25(OH)D with physical performance.
- Slow internal protein dynamics in solution. [Review]
- JPJ Phys Condens Matter 2014 Dec 17; 26(50):503103
- Large-scale domain dynamics in proteins are found when flexible linkers or hinges connect domains. The related conformational changes are often related to the function of the protein,for example by a…
Large-scale domain dynamics in proteins are found when flexible linkers or hinges connect domains. The related conformational changes are often related to the function of the protein,for example by arranging the active center after substrate binding or allowing transport and release of products. The adaptation of a specific active structure is referred to as ‘induced fit’ and is challenged by models such as ‘conformational sampling’. Newer models about protein unction include some flexibility within the protein structure or even internal dynamics of the protein. As larger domains contribute to the configurational changes, the timescale of the involved motions is slowed down. The role of slow domain dynamics is being increasingly recognized as essential to understanding the function of proteins. Neutron spin echospectroscopy (NSE) is a technique that is able to access the related timescales from 0.1 up to several hundred nanoseconds and simultaneously covers the length scale relevant for protein domain movements of several nanometers distance between domains. Here we focus on these large-scale domain fluctuations and show how the structure and dynamics of proteins can be assessed by small-angle neutron scattering and NSE.
- The unique case of the Niemann-Pick type C cholesterol storage disorder. [Review]
- PEPediatr Endocrinol Rev 2014; 12 Suppl 1:166-75
- Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal cholesterol storage disorder that arises from loss-of-f unction mutations in either the NPCI or NPC2 genes. Both genes code for proteins…
Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal cholesterol storage disorder that arises from loss-of-f unction mutations in either the NPCI or NPC2 genes. Both genes code for proteins involved in lysosomal cholesterol efflux. NPC is often diagnosed in early childhood, with patients typically displaying cerebellar ataxia, difficulties in Unfortunately, to date, there is no curative treatment for this devastating and fatal disorder, although several symptomatic manifestations of NPC are treatable. In this review, we discuss the cell biology of the disease, clinical aspects, diagnostic approaches, and current and potential therapeutic strategies against NPC.
- MicroRNA-350 induces pathological heart hypertrophy by repressing both p38 and JNK pathways. [Journal Article]
- BBBiochim Biophys Acta 2013; 1832(1):1-10
- Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-350…
Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-350 in the cardiac setting is still unclear. The objective of this study is to determine whether miR-350 alone can induce pathological cardiac hypertrophy by repressing the SAPK pathway in cardiomyocytes. Here we report that miR-350 plays a key role in determining pathological cardiomyocyte hypertrophy and apoptosis. Comprehensive microarray profiling of miRs and qPCR showed that this unique miRNA was significantly up-regulated in rat hearts in response to late-stage transverse aortic constriction. Western blotting and luciferase assays confirmed that the target mRNAs of miR-350 are mitogen activated protein kinase (MAPK) 11/14 and MAPK8/9 gene transcripts. Gain-of-unction and loss-of-function approaches were used to investigate the functional roles of miR-350. The forced over-expression of miR-350 was sufficient to induce hypertrophy of cardiomyocytes through the posttranslational suppression of p38 and JNK protein synthesis. Moreover, miR-350 led to an increase in unphosphorylated NFATc3 and its nuclear translocation, resulting in the over-expression of pathological hypertrophy markers. As predicted, these effects could effectively be imitated by siR-JNK/p38 through the degeneration of p38 and JNK mRNAs. Conversely, antagomir-350 could lower the levels of miR-350, reverse the expression of target proteins and reduce cell size and apoptosis relative to the administration of mutant antagomir-350. Our data provide the first evidence that miR-350 is a critical regulator of pathological cardiac hypertrophy and apoptosis in rats.
- Reproductive system behavior following exposure of sustained delivery of npy antagonist in ovariectomized (ovx) rats. [Journal Article]
- BSBiomed Sci Instrum 2012; 48:65-72
- Several investigations have documented that sustained delivery of estrogen can modulate or sustain normal female reproductive functions. However, the literature is lacking scientific evidence regard…
Several investigations have documented that sustained delivery of estrogen can modulate or sustain normal female reproductive functions. However, the literature is lacking scientific evidence regarding the mechanism of estrogen and neuropeptide Y antagonist (NPY) effect on the hypothalamic-pituitary-gonadal axis. The objective of this study was to explore the role of sustained delivery of estrogen and its effects on reproductive unction compared to an antagonist such as NPY. A total of twenty adult female rats (OVX, n=15; intact control, n=5) were divided into five groups (intact control, OVX, sham, OVX + estrogen, and OVX + NPY). Animals in two groups were surgically implanted with a TCP delivery device loaded with estrogen or NPY. Vaginal smears and body weights (BW) were evaluated at baseline and at two weeks post implantation. At the end of two weeks, all animals were euthanized and vital and reproductive organs were retrieved for histopathological evaluation. The results revealed differences in BW between intact control and OVX animals. Furthermore, there was statistical difference (P<0.05) in BW between OVX and OVX + NPY animals. Vaginal smear evaluation revealed that estrogen exposure induced estrus cyclic activities as compared to OVX and sham animals. The animals exposed to sustained delivery of NPY triggered moderate cyclic activities compared to intact control animals. There were no significant differences (P<0.5) in vital organ wet weights among and between animals in all groups. Overall this study proved the capability of TCP to release estrogen and NPY at sustained levels, which resulted inpathophysiological changes in female reproductive organs.
- Caryodendron orinocense ('nuez de Barinas') oil: tocopherol content and use in cosmetics. [Journal Article]
- IJInt J Cosmet Sci 2000; 22(5):335-40
- Preliminary studies showed the possibility of using the oil extracted from the 'nuez de Barinas' (Caryodendron orinocense Karst.) (also known as 'taque nut'), in cosmetic formulation, due to its UV a…
Preliminary studies showed the possibility of using the oil extracted from the 'nuez de Barinas' (Caryodendron orinocense Karst.) (also known as 'taque nut'), in cosmetic formulation, due to its UV absorbance spectrum as well as other physical, chemical and toxicological characteristics. Some Amerindians have used this oil as unction. The tree, also called in Venezuela 'nueza' or 'nogal de Barquisimeto', and in other countries 'Inchi' or 'taque', belongs to the Euphorbiaceae, and grows wild along the base of the Andes mountains in Venezuela, Ecuador, Peru and Colombia. The oil presented a high polyunsaturated fatty acid content, especially linoleic acid (75.13%), which makes it susceptible to oxidation. alpha, beta, gamma and delta-tocopherols are chemical compounds that have antioxidant and vitamin E activity. Tocopherols are used in cosmetics owing to these two characteristics. These properties vary depending on the isomer, the alpha-tocopherol having higher vitamin activity, while the delta-tocopherol has the highest antioxidant power, acting as free radical scavenger. The objective of this study was to assess the presence of tocopherols in the oil, as well as the emollient efficiency and activity of the oil after incorporation as a base in formulation of cosmetic products. Results showed good emollient efficiency and activity, and the presence of alpha, beta, gamma and delta-tocopherols, which means that the oil will be stable in cosmetic formulations.
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- A randomized, open-label, multicenter trial comparing once-a-day AVINZA (morphine sulfate extended-release capsules) versus twice-a-day OxyContin (oxycodone hydrochloride controlled-release tablets) for the treatment of chronic, moderate to severe low back pain: improved physical functioning in the ACTION trial. [Randomized Controlled Trial]
- JOJ Opioid Manag 2007 Jan-Feb; 3(1):35-43
- This multicenter trial compared the efficacy, safety, and effect on quality of life and work limitation of once-daily extended-release morphine sulfate capsules (AVINZA, A-MQD) and twice-daily contro…
This multicenter trial compared the efficacy, safety, and effect on quality of life and work limitation of once-daily extended-release morphine sulfate capsules (AVINZA, A-MQD) and twice-daily controlled-release oxycodone HCI tablets (OxyContin, O-ER) in subjects with chronic, moderate to severe low back pain. After randomization and a period of opioid dose titration, subjects (n=266) underwent an eight-week evaluation phase and an optionalf our-month extension phase (n=174 in extension phase). Subjects were assessed using the 12-item Short-Form Health Survey (SF-12) and the Work Limitations Questionnaire (WLQ). In both groups, significant improvements were observed in the SF-12 mean scores forp hysicalf unctioning (p < 0.001), role physical (p < 0.0001), bodilyp ain (p < 0.0001), physical summary (p < 0.001), and mental component summary (p < 0.005). At the end of the titration period, greater relative improvements from baseline were seen in the SF-12 section on physical components in the A-MQD group versus the O-ER group, with significant differences observed for physical functioning (p = 0.0374), role physical (p = 0.0341), bodily pain (p = 0.0001), andp hysical summary (p = 0.0022). In both groups, SF-12 mean scores improved significantly for mental health (p < 0.01), role emotional (p < 0.01), socialfunctioning (p < 0.0005), vitality (p < 0.005), and the mental component summary (p < 0.005), but no significant differences were noted between the two groups. Both groups reported improvement from baseline in WLQ physical demands scores, with no significant differences noted between the two groups. At the end of the evaluation phase, fewer subjects were unable to work due to illness or treatment in the A-MQD group than in the O-ER group (8.5 percent versus 19.4 percent, respectively; p = 0.0149). In conclusion, compared to twice-daily OxyContin, once-daily A VINZA resulted in significantly better and earlier improvement ofp hysicalf unction and ability to work.