Lamgibson5181

The purpose of this study was to investigate whether low-level light therapy (LLLT) was capable of modulating expression of ultraviolet (UV) light-responsive genes in vivo.

The effects of 670 nm light-emitting diode (LED) array irradiation were investigated in a hairless SHK-1 mouse epidermis model. Mice were given a single dose of UVA/UVB light, or three doses of red light (670 nm @ 8 mW/cm(2) x 312 sec, 2.5 J/cm(2) per session) spread over 24 h along with combinations of pre- and post-UV treatment with red light. Levels of 14 UV-responsive mRNAs were quantified 24 h after UV irradiation by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).

The transcription of mRNAs encoding for cluster of differentiation molecule 11b (CD11b) (p < 0.05) and interferon (IFN)-γ (p < 0.012) increased after irradiation with red light alone, whereas expression level of cyclooxygenase (COX)-2 (p < 0.02) was downregulated. Genes unresponsive to UV did not change their expression levels after exposure to red light either. Pretreatment with red light significantly modified response of Fos to UV exposure (p < 0.01). A synergy of UV and post-treatment with red light in reducing the transcription levels of CD11b (p < 0.05) and inducible nitric oxide synthase (iNOS) (p < 0.05) was observed.

This is an initial observation that in mouse red light LLLT more often than not causes opposite gene expression changes or reduces those caused by moderate UVA-UVB irradiation.

This is an initial observation that in mouse red light LLLT more often than not causes opposite gene expression changes or reduces those caused by moderate UVA-UVB irradiation.

Gabapentin (GBP), originally an antiepileptic drug, is more commonly used in the treatment of pain, including headache disorders. Off-label GBP is used in headache disorders with some success, some failure, and much debate. Due to this ambiguity, a clinical evidence literature review was performed investigating GBP's efficacy in headache disorders.

Bibliographic reference searches for GBP use in headache disorders were performed in PUBMED and OVID Medline search engines from January 1, 1983 to August 31, 2014. Based on abstracts read by two reviewers, references were excluded if GBP was not a study compound or headache symptoms were not studied. The resulting references were then read, reviewed, and analyzed.

Fifty-six articles pertinent to GBP use in headache disorders were retained. Eight headache clinical trials were quality of evidence Class 2 or higher based on American Academy of Neurology criteria. Seven of the eight clinical trials showed statistically significant clinical benefit from GBP in various headache syndromes (though modest affects at times). One study, Mathew et al., had concerns about intention-treat analysis breaches and primary outcomes.

Despite the conflicting evidence surrounding select studies, a significant amount of evidence shows that GBP has benefit for a majority of primary headache syndromes, including chronic daily headaches. GBP has some efficacy in migraine headache, but not sufficient evidence to suggest primary therapy. selleck kinase inhibitor When primary headache treatments fail, a GBP trial may be considered in the individual patient.

Despite the conflicting evidence surrounding select studies, a significant amount of evidence shows that GBP has benefit for a majority of primary headache syndromes, including chronic daily headaches. GBP has some efficacy in migraine headache, but not sufficient evidence to suggest primary therapy. When primary headache treatments fail, a GBP trial may be considered in the individual patient.Hematopoietic stem cell transplantation (HSCT) is currently the only available curative therapy for X-linked inhibitor of apoptosis (XIAP) deficiency. Myeloablative conditioning regimens are associated with high mortality rates. Reduced-intensity conditioning (RIC) is recommended in order to decrease treatment-related toxicities, but RIC regimens increase the risk for mixed donor-recipient chimerism that may progress to graft loss. We report our experience with a patient with XIAP deficiency who was successfully treated with allogeneic HSCT using a RIC protocol. Post-transplant chimerism was vigilantly monitored and maintained with donor lymphocyte infusions and a stem cell boost to a level that prevented hemophagocytic lymphohistiocytosis recurrence.An original approach is proposed to investigate inorganic (iHg) and methylmercury (MeHg) trophic transfer and fate in a model fish, Danio rerio, by combining natural isotopic fractionation and speciation. Animals were exposed to three different dietary conditions (1) 50 ng Hg g(-1), 80% as MeHg; (2) diet enriched in MeHg 10,000 ng Hg g(-1), 95% as MeHg, and (3) diet enriched in iHg 10,000 ng Hg g(-1), 99% as iHg. Harvesting was carried out after 0, 7, 25, and 62 days. Time-dependent Hg species distribution and isotopic fractionation in fish organs (muscle, brain, liver) and feces, exhibited different patterns, as a consequence of their dissimilar metabolization. The rapid isotopic re-equilibration to the new MeHg-food source reflects its high bioaccumulation rate. Relevant aspects related to Hg excretion are also described. This study confirms Hg isotopic fractionation as a powerful tool to investigate biological processes, although its deconvolution and fully understanding is still a challenge.The conduction channel of a graphene field-effect transistor (FET) is decoupled from the parasitic charge impurities of the underlying substrate. Fluorographene as a passivation layer is fabricated between the oxide substrate and channel, and a self-aligned gate-terminated FET is also fabricated. This approach significantly reduces the scattering and, as a result, the mobility increases ten fold.The hammerhead ribozyme is a self-cleaving RNA broadly dispersed across all kingdoms of life. Although it was the first of the small, nucleolytic ribozymes discovered, the mechanism by which it catalyzes its reaction remains elusive. The nucleobase of G12 is well positioned to be a general base, but it is unclear if or how this guanine base becomes activated for proton transfer. Metal ions have been implicated in the chemical mechanism, but no interactions between divalent metal ions and the cleavage site have been observed crystallographically. To better understand how this ribozyme functions, we have solved crystal structures of wild-type and G12A mutant ribozymes. We observe a pH-dependent conformational change centered around G12, consistent with this nucleotide becoming deprotonated. Crystallographic and kinetic analysis of the G12A mutant reveals a Zn(2+) specificity switch suggesting a direct interaction between a divalent metal ion and the purine at position 12. The metal ion specificity switch and the pH-rate profile of the G12A mutant suggest that the minor imino tautomer of A12 serves as the general base in the mutant ribozyme. We propose a model in which the hammerhead ribozyme rearranges prior to the cleavage reaction, positioning two divalent metal ions in the process. The first metal ion, positioned near G12, becomes directly coordinated to the O6 keto oxygen, to lower the pKa of the general base and organize the active site. The second metal ion, positioned near G10.1, bridges the N7 of G10.1 and the scissile phosphate and may participate directly in the cleavage reaction.This Article reported the fabrication of a robust theranostic cerasome encapsulating indocyanine green (ICG) by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)2000]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid monoamide (DSPE-PEG2000-DOTA), followed by chelating radioisotope of (177)Lu. Its applications in optical and nuclear imaging of tumor uptake and biodistribution, as well as photothermal killing of cancer cells, were investigated. It was found that the obtained cerasome could act efficiently as fluorescence contrast agent as well as nuclear imaging tracer. Encapsulating ICG into cerasome could protect ICG from degradation, aggregation, and fast elimination from body, resulting in remarkable improvement in near-infrared fluorescence imaging, photothermal stability, and in vivo pharmacokinetic profile. Both fluorescence and nuclear imaging showed that such agent could selectively accumulate in tumor site after intravenous injection of the cerasome agent into Lewis lung carcinoma tumor bearing mice, resulting in efficient photothermal ablation of tumor through a one-time NIR laser irradiation at the best time window. The ability to track the uptake of cerasomes on a whole body basis could provide researchers with an excellent tool for developing cerasome-based drug delivery agents, especially the strategy of labeling cerasomes with theranostic radionuclide (177)Lu, enabling the ability of the (177)Lu-labeled cerasomes for radionuclide cancer therapy and even the combined therapy.

Blinding ocular herpetic disease in humans is due to spontaneous reactivation of herpes simplex virus type 1 (HSV-1) from latency, rather than to primary acute infection. Mice latently infected with HSV-1 undergo little or no in vivo spontaneous reactivation with accompanying virus shedding in tears. HSV-1 reactivation can be induced in latently infected mice by several in vivo procedures, with UV-B-induced reactivation being one commonly used method. In the UV-B model, corneas are scarified (lightly scratched) just prior to ocular infection to increase efficiency of the primary infection and immune serum containing HSV-1 neutralizing antibodies is injected intraperitoneally (i.p.) to increase survival and decrease acute corneal damage. Since scarification can significantly alter host gene transcription in the cornea and in the trigeminal ganglia (TG; the site of HSV-1 latency) and since injection of immune serum likely modulates innate and adaptive herpes immunity, we investigated eliminating both treatments.

Mice were infected with HSV-1 with or without corneal scarification and immune serum. HSV-1 reactivation and recurrent disease were induced by UV-B irradiation.

When corneal scarification and immune serum were both eliminated, UV-B irradiation still induced both HSV-1 reactivation, as measured by shedding of reactivated virus in tears and herpetic eye disease, albeit at reduced levels compared to the original procedure.

Despite the reduced reactivation and disease, avoidance of both corneal scarification and immune serum should improve the clinical relevance of the UV-B mouse model.

Despite the reduced reactivation and disease, avoidance of both corneal scarification and immune serum should improve the clinical relevance of the UV-B mouse model.Epithelial membrane protein 3 (EMP3) is a transmembrane signaling molecule, which is important in the regulation of apoptosis, differentiation and invasion of cancer cells. However, the specific function and regulatory mechanism of EMP3 in primary breast carcinoma remain to be elucidated. In the present study, the mRNA and protein levels of EMP3 were observed to be upregulated in primary breast carcinoma tissues, compared with normal tissues. It was hypothesized that the overexpression of EMP3 was correlated with the downregulation of microRNA‑765 (miR‑765), an underexpressed miRNA in primary breast carcinoma tissues. Functional analysis demonstrated that EMP3 was regulated by miR‑765 through binding to its 3'untranslated region. In addition, the knockdown of EMP3 and miR‑765 had similar effects on the inhibition of proliferation and invasion in SK‑BR‑3 cells. These results provided novel insight into the regulatory mechanism of EMP3 in primary breast carcinoma.