Adipose-derived human mesenchymal stem cells seeded on denuded or stromal sides of the amniotic membrane improve angiogenesis and collagen remodeling and accelerate healing of the full-thickness wound.

Several strategies have been proposed to enhance wound healing results. Along with other forms of wound dressing, the human amniotic membrane (HAM) has long been regarded as a biological wound dressing that decreases infection and enhances healing. This study investigates the feasibility and effectiveness of wound healing using decellularized HAM (dAM) and stromal HAM (sAM) in combination with adipose-derived human mesenchymal stem cells (AdMSCs). The dAM and sAM sides of HAM were employed as wound dressing scaffolds, and AdMSCs were seeded on top of either dAM or sAM. Sixty healthy Wistar rats were randomly divided into three groups: untreated wound, dAM/AdMSCs group, and sAM/AdMSCs group. The gene expression of VEGF and COL-I was measured in vitro. Wound healing was examined after wounding on days 3, 7, 14, and 21. The expression level of VEGF was significantly higher in sAM/AdMSCs than dAM/AdMSCs (P ≤ 0.05), but there was no significant difference in COL-I expression (P ≥ 0.05). In vivo research revealed that on day 14, wounds treated with sAM/AdMSCs had more vascularization than wounds treated with dAM/AdMSCs (P ≤ 0.01) and untreated wound groups on days 7 (P ≤ 0.05) and 14 (P ≤ 0.0001), respectively. On days 14 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), and 21 (P < 0.05 for sAM/AdMSCs, P < 0.01 for dAM/AdMSCs), the collagen deposition in the wound bed was significantly thicker in the sAM/AdMSCs and dAM/AdMSCs groups compared to untreated wounds. The study demonstrated that the combination of sAM and AdMSCs promotes wound healing by enhancing angiogenesis and collagen remodeling.

Positive anxiety or depression screen despite ongoing antidepressant prescription in people with epilepsy: A large cross-sectional analysis.

Purpose: While antidepressants are recommended to manage anxiety or depression in epilepsy, limited effectiveness data exist in real-world epilepsy samples, and prior work indicated frequent positive screens despite antidepressant prescription. In response, this study evaluates factors associated with positive anxiety or depression screen during ongoing antidepressant prescription. Methods: Clinical and sociodemographic characteristics were collected among consecutive adult epilepsy clinic patients completing validated anxiety and depression instruments. The sample was divided by presence vs absence of existing antidepressant prescription at time of screening. Among those on an antidepressant, multivariable logistic regression was performed on pre-selected characteristics to evaluate for association with positive anxiety and/or depression screen. Pre-selected characteristics included: antidepressant dose, antidepressant prescriber specialty, antiseizure medications (number, potential psychotropic effects), seizure frequency, employment, visit no-shows, and medical insurance. Results: Of 563 people with epilepsy, 152 had evidence of antidepressant prescription at time of screening and 73/152(48%) had positive anxiety and/or depression screen. Multivariable modeling demonstrated low antidepressant dose and no-show visit(s) were associated with positive screens (adjusted OR 2.29, CI 1.00-5.48 and 3.11, 1.26-8.22 respectively). Conclusion: Low antidepressant dose and factors potentially associated with adherence (visit no-shows) may contribute to persistent anxiety and/or depression among epilepsy patients on an antidepressant.

Neurologist prescribing versus psychiatry referral: Examining patient preferences for anxiety and depression management in a symptomatic epilepsy clinic sample.

OBJECTIVE: Anxiety and depression symptoms in epilepsy are common, impactful and under-recognized and undertreated. While prior survey data suggests equipoise among epileptologists for managing anxiety and/or depression via prescribing in the epilepsy clinic versus psychiatry referral, patient preferences are unknown and should potentially influence practice habits among epileptologists. Thus, the primary objective of this study was to determine patient preference for anxiety and/or depression prescribing by neurologists versus psychiatry referral among an adult epilepsy clinic sample of symptomatic patients. METHODS: Management preferences for anxiety and/or depression were surveyed in an adult tertiary care epilepsy clinic. Individuals who screened positive for anxiety and/or depression symptoms on validated instruments during a routine care-embedded learning health system study were recruited. Demographics, social variables, psychiatric treatment history, and treatment priorities and preferences were surveyed. Preference was defined as a slightly greater than 2:1 ratio in favor neurology prescribing or psychiatry referral. The study was powered to assess this primary objective using a two-sample binomial test. Multinomial logistic regression examined an a priori multivariable model of treatment preference (secondary objective). RESULTS: The study sample included N = 63 symptomatic adults, with 64% women and mean age 42.2 years. Most reported past or current treatment for anxiety and/or depression, and treatment for these symptoms was a high or moderate priority among 65.1% of the sample. Neurologist prescribing was preferred in 83.0% (nearly 5:1) over psychiatry referral among those who chose neurology or psychiatry (as opposed to neither of the two; p < 0.001, 95% CI 0.702-0.919). Overall, 69.8% of the total study sample preferred neurology prescribing. Multivariable modeling indicated preference for neither management option (compared with neurologist prescribing) was associated with low overall treatment prioritization and having never received neurologist medication management. None of the factors examined in the a priori multivariable model were associated with selecting psychiatry referral (compared to neurologist prescribing). CONCLUSION: In this sample, most patients indicated a preference for neurologists to prescribe for anxiety or depression symptoms in the epilepsy clinic. Care models involving neurologist prescribing for anxiety and depression symptoms merit further investigation and potential adoption in clinical practice.

Exposure to suboptimal ambient temperature during specific gestational periods and adverse outcomes in mice.

Exposure to suboptimal ambient temperature during pregnancy has been reported as a potential teratogen of fetal development. However, limited animal evidence is available regarding the impact of extreme temperatures on maternal pregnancy and the subsequent adverse pregnancy outcomes. Our objective in this study is to investigate the relationship between temperature and maternal stress during pregnancy in mice. This study used the Naval Medical Research Institute (NMRI) mice during the second and third pregnant weeks with the gestational day (GD) (GD 6.5-14.5 and GD 14.5-17.5). Mice were exposed to suboptimal ambient temperature (1 °C, 5 °C, 10 °C, 15 °C, 40 °C, 42 °C, 44 °C, 46 °C, and 48 °C for the experimental group and 23 °C for the control group) 1 h per day, 7 days a weekin each trimester. Measurements of placental development (placental weight [PW] and placental diameter [PD]) and fetal growth (fetal weight [FW] and crown-to-rump length [CRL]) between experimental and control groups were compared using analysis of variance (ANOVA). Data on the occurrence of preterm birth (PTB) and abnormalities were also collected. The results showed that exposure to both cold and heat stress in the second and third weeks of pregnancy caused significant decreases in measurements of placental development (PW and PD) and fetal growth (FW and CRL). For all temperature exposures, 15 °C was identified as the optimal temperature in the development of the embryo. Most PTB occurrences were observed in high-temperature stress groups, with the highest PTB number seen in the exposure group at 48 °C, whereas PTB occurred only at 1 °C among cold stress groups. In the selected exposure experiments, an approximate U-shaped relation was observed between temperature and number of abnormality occurrence. The highest percentage of these anomalies occurred at temperatures of 1 °C and 48 °C, while no abnormalities were observed at 15 °C and in the control group. Our findings strengthened the evidence that exposure to suboptimal ambient temperatures may trigger adverse pregnancy outcomes and worsen embryo and fetal development in mice.

The chromatin-remodeling complexes B-WICH and NuRD regulate ribosomal transcription in response to glucose.

Regulation of ribosomal transcription is under tight control from environmental stimuli, and this control involves changes in the chromatin structure. The underlying mechanism of how chromatin changes in response to nutrient and energy supply in the cell is still unclear. The chromatin-remodeling complex B-WICH is involved in activating the ribosomal transcription, and we show here that knock down of the B-WICH component WSTF results in cells that do not respond to glucose. The promoter is less accessible, and RNA pol I and its transcription factors SL1/TIF-1B and RRN3/TIF-1A, as well as the proto-oncogene c-MYC and the activating deacetylase SIRT7 do not bind upon glucose stimulation. In contrast, the repressive chromatin state that forms after glucose deprivation is reversible, and RNA pol I factors are recruited. WSTF knock down results in an accumulation of the ATPase CHD4, a component of the NuRD chromatin remodeling complex, which is responsible for establishing a repressive poised state at the promoter. The TTF-1, which binds and affect the binding of the chromatin complexes, is important to control the association of activating chromatin component UBF. We suggest that B-WICH is required to allow for a shift to an active chromatin state upon environmental stimulation, by counteracting the repressive state induced by the NuRD complex.

Mechanisms and Uses of Dietary Therapy as a Treatment for Epilepsy: A Review.

One-third of patients with epilepsy do not respond to antiepileptic drugs and may seek complementary and alternative treatment modalities. Dietary therapies such as the ketogenic diet (KD), the modified Atkins, the medium-chain triglyceride, and the low glycemic index diet have been successfully implemented in some forms of epilepsy and are growing in utilization. The KD is a high-fat, low-protein, low-carbohydrate diet that has been used for various conditions for over a century. Insights into the mechanism of action of these diets may provide more targeted interventions for patients with epilepsy. Knowledge of these mechanisms is growing and includes neuroprotective effects on oxidative stress, neuroinflammation, potassium channels in the brain, and mitochondrial function.

Complementary and Alternative Medicine for Painful Peripheral Neuropathy.

PURPOSE OF REVIEW: The purpose of our manuscript is to review the current evidence supporting the use of complementary and alternative medicine (CAM) in neuromuscular disease, specifically in painful peripheral neuropathy (PPN). We outline the therapeutic challenges of this debilitating condition and describe the best evidence for incorporating such therapies into clinical practice. The most studied modalities include lifestyle modifications with diet and exercise, supplements, and acupuncture. CAM therapies such as yoga, meditation, electrical stimulation, neuromodulatory devices, and cannabis are mentioned as emerging therapies. RECENT FINDINGS: Current data suggests that targeted lifestyle modifications, including aerobic exercise and diet modifications that promote weight loss, may improve the natural course of diabetic painful neuropathy and potentially other types of neuropathy. A number of studied dietary supplements and vitamins including B vitamins, vitamin D, alpha-lipoic acid, and acetyl-L-carnitine improve both subjective and objective neuropathic measures. A wide range of neuromodulatory devices and electrical stimulation modalities demonstrate mixed results, and further studies are needed to confirm their benefit. Finally, acupuncture and yoga both demonstrate benefit in a variety of PPNs. Multiple CAM therapies show efficacy in the treatment of PPN. From the strongest level of evidence to the least, lifestyle modifications including exercise and diet; supplements including B12, alpha lipoic acid, acetyl-L-carnitine, and vitamin D in deficient patients; followed by acupuncture and yoga may alleviate symptoms of PPN.

Surface modification of nanosatrch using nano silver: a potential antibacterial for food package coating.

Starch nanocrystal was prepared using weak sulfuric acid hydrolysis at 40 °C. Transmission electron micrographs of dilute suspensions of starch nanocrystals showed round particles with a diameter ranging from 20 to 40 nm. SEM of freeze dried samples showed separated particles between 40 and 100 nm and confirmed production of starch nano particles. XRD patterns obtained for the prepared nanostarch and raw starch sample showed no special pattern of crystallinity for starch sample. Extracted nanostarch showed pattern of crystallinity with the peaks at Bragg angles (2θ) at about 15° and 23°, and a doublet at 17° and 18°. The crystalline structure of prepared sample was A-type. FTIR spectra confirmed the particles oxidation. Nano silver particle was precipitated on the starch nano particle. UV spectra confirmed the presence of silver particle on the starch particles. Inhibitions tests of nanostarch bearing nano silver on three types of bacteria was investigated. The inhibition test results were 25 µg/mL for S. aureus, and S. typhi, and 12.5 µg/mL for E. coli.

Extracellular biosynthesis of magnetic iron oxide nanoparticles by Bacillus cereus strain HMH1: Characterization and in vitro cytotoxicity analysis on MCF-7 and 3T3 cell lines.

Discovery of new properties and special functionalities at the nanoscale materials caused nanotechnology to become one of the leading parts in all sciences namely biology and medicine. Magnetic iron oxide nanoparticles (MIONPs) are among interesting nanomaterials in biomedical arena, which have attracted the attention of many researchers owing to their extensive capabilities. Due to the simple, cost-effective and environmentally-friendly production processes, biosynthesis is of paramount importance between different methods of nanoparticles production. In the current study, we succeeded to synthesize MIONPs using a newly extracted bacteria supernatant. Produced nanoparticles were characterized using FE-SEM, DLS, VSM, UV-vis, FT-IR and EDS spectroscopy. Analysis showed that the average particle size of very stable spherical MIONPs is about 29.3 nm. The bacteria protein profile obtained by SDS-PAGE analysis indicated induction of different proteins. In vitro cytotoxicity of nanoparticles on the viability of MCF7 and 3T3 cell lines was assessed by MTT assay. The results show that toxicity of the produced nanoparticles (IC50, MCF-7 > 5 mg/ml and IC50, 3T3 > 7.5 mg/ml) follows a concentration dependent manner.

The B-WICH chromatin-remodelling complex regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding.

The chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. However, the underlying mechanism is unknown. Using high-resolution MN walking we demonstrate here that B-WICH changes the chromatin structure in the vicinity of the 5S rRNA and 7SL RNA genes during RNA polymerase III transcription. The action of B-WICH is required for the binding of the RNA polymerase machinery and the regulatory factors c-Myc at the 5S rRNA and 7SL RNA genes. In addition to the c-Myc binding site at the 5S genes, we have revealed a novel c-Myc and Max binding site in the intergenic spacer of the 5S rDNA. This region also contains a region remodelled by B-WICH. We demonstrate that c-Myc binds to both sites in a Max-dependent way, and thereby activate transcription by acetylating histone H3. The novel binding patterns of c-Myc and Max link transcription of 5S rRNA to the Myc/Max/Mxd network. Since B-WICH acts prior to c-Myc and other factors, we propose a model in which the B-WICH complex is required to maintain an open chromatin structure at these RNA polymerase III genes. This is a prerequisite for the binding of additional regulatory factors.

Nuclear myosin 1c facilitates the chromatin modifications required to activate rRNA gene transcription and cell cycle progression.

Actin and nuclear myosin 1c (NM1) cooperate in RNA polymerase I (pol I) transcription. NM1 is also part of a multiprotein assembly, B-WICH, which is involved in transcription. This assembly contains the chromatin remodeling complex WICH with its subunits WSTF and SNF2h. We report here that NM1 binds SNF2h with enhanced affinity upon impairment of the actin-binding function. ChIP analysis revealed that NM1, SNF2h, and actin gene occupancies are cell cycle-dependent and require intact motor function. At the onset of cell division, when transcription is temporarily blocked, B-WICH is disassembled due to WSTF phosphorylation, to be reassembled on the active gene at exit from mitosis. NM1 gene knockdown and motor function inhibition, or stable expression of NM1 mutants that do not interact with actin or chromatin, overall repressed rRNA synthesis by stalling pol I at the gene promoter, led to chromatin alterations by changing the state of H3K9 acetylation at gene promoter, and delayed cell cycle progression. These results suggest a unique structural role for NM1 in which the interaction with SNF2h stabilizes B-WICH at the gene promoter and facilitates recruitment of the HAT PCAF. This leads to a permissive chromatin structure required for transcription activation.

The chromatin remodelling complex B-WICH changes the chromatin structure and recruits histone acetyl-transferases to active rRNA genes.

The chromatin remodelling complex B-WICH, which comprises the William syndrome transcription factor (WSTF), SNF2h, and nuclear myosin 1 (NM1), is involved in regulating rDNA transcription, and SiRNA silencing of WSTF leads to a reduced level of 45S pre-rRNA. The mechanism behind the action of B-WICH is unclear. Here, we show that the B-WICH complex affects the chromatin structure and that silencing of the WSTF protein results in a compaction of the chromatin structure over a 200 basepair region at the rRNA promoter. WSTF knock down does not show an effect on the binding of the rRNA-specific enhancer and chromatin protein UBF, which contributes to the chromatin structure at active genes. Instead, WSTF knock down results in a reduced level of acetylated H3-Ac, in particular H3K9-Ac, at the promoter and along the gene. The association of the histone acetyl-transferases PCAF, p300 and GCN5 with the promoter is reduced in WSTF knock down cells, whereas the association of the histone acetyl-transferase MOF is retained. A low level of H3-Ac was also found in growing cells, but here histone acetyl-transferases were present at the rDNA promoter. We propose that the B-WICH complex remodels the chromatin structure at actively transcribed rRNA genes, and this allows for the association of specific histone acetyl-transferases.

Distinct functions of the Drosophila Nup153 and Nup214 FG domains in nuclear protein transport.

The phenylanine-glycine (FG)-rich regions of several nucleoporins both bind to nuclear transport receptors and collectively provide a diffusion barrier to the nuclear pores. However, the in vivo roles of FG nucleoporins in transport remain unclear. We have inactivated 30 putative nucleoporins in cultured Drosophila melanogaster S2 cells by RNA interference and analyzed the phenotypes on importin alpha/beta-mediated import and CRM1-dependent protein export. The fly homologues of FG nucleoporins Nup358, Nup153, and Nup54 are selectively required for import. The FG repeats of Nup153 are necessary for its function in transport, whereas the remainder of the protein maintains pore integrity. Inactivation of the CRM1 cofactor RanBP3 decreased the nuclear accumulation of CRM1 and protein export. We report a surprisingly antagonistic relationship between RanBP3 and the Nup214 FG region in determining CRM1 localization and its function in protein export. Our data suggest that peripheral metazoan FG nucleoporins have distinct functions in nuclear protein transport events.