Male rat hypothalamic extraretinal photoreceptor Opsin3 is sensitive to osmotic stimuli and light.

The light-sensitive protein Opsin 3 (Opn3) is present throughout the mammalian brain; however, the role of Opn3 in this organ remains unknown. Since Opn3 encoded mRNA is modulated in the supraoptic and paraventricular nucleus of the hypothalamus in response to osmotic stimuli, we have explored by in situ hybridization the expression of Opn3 in these nuclei. We have demonstrated that Opn3 is present in the male rat magnocellular neurones expressing either the arginine vasopressin or oxytocin neuropeptides and that Opn3 increases in both neuronal types in response to osmotic stimuli, suggesting that Opn3 functions in both cell types and that it might be involved in regulating water balance. Using rat hypothalamic organotypic cultures, we have demonstrated that the hypothalamus is sensitive to light and that the observed light sensitivity is mediated, at least in part, by Opn3. The data suggests that hypothalamic Opn3 can mediate a light-sensitive role to regulate circadian homeostatic processes.

Light-sensitive circuits related to emotional processing underlie the antidepressant neural targets of light therapy.

Since Aaron Beck proposed his cognitive model of depression, biased attention, biased processing, and biased rumination (different phases of biased cognition) have been considered as the key elements consistently linked with depression. Increasing evidence suggests that the functional failures in the "emotional processing system (EPS)" underlie the neurological foundation of the biased cognition of depression. Light therapy, a non-intrusive approach, exerts powerful effects on emotion and cognition and affects the activity, functional connectivity, and plasticity of multiple brain structures. Although numerous studies have reported its effectiveness in treating depression, the findings have not been integrated with Beck's cognitive model and EPS, and the neurobiological mechanisms of antidepressant light therapy remain largely unknown. In this review, integrated with the classical theories of Beck's cognitive model of depression and EPS, we identified the key neural circuits and abnormalities involved in the cognitive bias of depression and, accordingly, identified and depicted several light-sensitive circuits (LSCs, neural circuits in the EPS that are responsive to light stimulation) that may underlie the antidepressant neural targets of light therapy, as listed below: In summary, the LSCs above narrow down the research scope of identifying the neural targets of antidepressant light therapy and help elucidate the neuropsychological mechanism of antidepressant light therapy.

Prodrugs of hydrogen sulfide and related sulfur species: recent development.

Hydrogen sulfide (H2S) is commonly referred to as the third gasotransmitter with firmly established physiological roles. Prodrug approaches have been broadly applied to deliver H2S for various applications and mechanistic studies. Since S-persulfidation and glutathionylation are known to be important in cellular signaling by sulfur species, there have been interests in developing donors of persulfide and glutathione persulfide as well. In this review, we discuss the recent development in area of prodrugs for various sulfur species.

Influence of Chloroplast Defects on Formation of Jasmonic Acid and Characteristic Aroma Compounds in Tea (Camellia sinensis) Leaves Exposed to Postharvest Stresses.

Characteristic aroma formation in tea (Camellia sinensis) leaves during the oolong tea manufacturing process might result from the defense responses of tea leaves against these various stresses, which involves upregulation of the upstream signal phytohormones related to leaf chloroplasts, such as jasmonic acid (JA). Whether chloroplast changes affect the formation of JA and characteristic aroma compounds in tea leaves exposed to stresses is unknown. In tea germplasms, albino-induced yellow tea leaves have defects in chloroplast ultrastructure and composition. Herein, we have compared the differential responses of phytohormone and characteristic aroma compound formation in normal green and albino-induced yellow tea leaves exposed to continuous wounding stress, which is the main stress in oolong tea manufacture. In contrast to single wounding stress (from picking, as a control), continuous wounding stress can upregulate the expression of CsMYC2, a key transcription factor of JA signaling, and activate the synthesis of JA and characteristic aroma compounds in both normal tea leaves (normal chloroplasts) and albino tea leaves (chloroplast defects). Chloroplast defects had no significant effect on the expression levels of CsMYC2 and JA synthesis-related genes in response to continuous wounding stress, but reduced the increase in JA content in response to continuous wounding stress. Furthermore, chloroplast defects reduced the increase in volatile fatty acid derivatives, including jasmine lactone and green leaf volatile contents, in response to continuous wounding stress. Overall, the formation of metabolites derived from fatty acids, such as JA, jasmine lactone, and green leaf volatiles in tea leaves, in response to continuous wounding stress, was affected by chloroplast defects. This information will improve understanding of the relationship of the stress responses of JA and aroma compound formation with chloroplast changes in tea.

Near infrared light-triggered nanoparticles using singlet oxygen photocleavage for drug delivery systems.

Drug delivery systems (DDSs) have showed a reduced systemic toxicity and enhanced therapeutic efficacy over conventional cancer treatments. However, after reaching the damaged tissue, DDSs should present a trigger release of the encaged therapeutics. Among all methodologies for a controlled release system, the use of light in NIR window (650-900 nm) shows the most appropriate characteristics for biological applications (e.g. biocompatibility with tissues). This review is focused on NIR responsive approaches for DDSs intermediated by a photosensitizer (PS) using nanoparticles (NP) that possess oxidation sensitive segments. After excited by light, the PS generates singlet oxygen species which interact with a sensitive segment, causing bond cleavage or hydrophobicity change in NP followed by the release of entrapped therapeutics. The most relevant sensitive segments addressed in this work are: olefin (lipid, vinyl ether, vinyl disulfide, and aminoacrylate), thioketal, selenium and hydrophobicity changeable polymers (tellurium, poly(propylene sulfide), imidazole and nitroimidazole). The chemical structure of the sensitive segment, the available strategies for nanoparticle formation and DDSs in vitro and in vivo studies are also critically discussed. These NIR responsive DDSs have enormous potential as a tool for a controlled spatial-temporal drug release with capacity to overcome the drawbacks of the others specificity target DDSs (such as pH, temperature and ROS). In order to reach the pharmacological market, the light sensibility of the labile segments should increase for the range of wavelengths used and more biological test should be addressed.

Differential Accumulation of Aroma Compounds in Normal Green and Albino-Induced Yellow Tea (Camellia sinensis) Leaves.

Tea (Camellia sinensis) cultivars with green leaves are the most widely used for making tea. Recently, tea mutants with white or yellow young shoots have attracted increasing interest as raw materials for making "high-quality" tea products. Albino teas are generallycharacterized as having metabolites of relatively high amino acid content and lower catechin content. However, little is known about aroma compounds in albino tea leaves. Herein, we compared original normal leaves (green) and light-sensitive albino leaves (yellow) of cv. Yinghong No. 9. GC-MS was employed to analyze endogenous tea aroma compounds and related precursors. Quantitative real time PCR was used to measure expression levels of genes involved in biosyntheses of tea aromas.The total contents of most endogenous free tea aromas, including aroma fatty acid derivatives, aroma terpenes, and aroma phenylpropanoids/benzenoids, and their glycosidically bound aroma compounds, were lower in yellow leaves than in green leaves. The content of the key precursor geranyl diphosphate (GDP) and expression levels of key synthetic genes involved in the formation of linalool, a major aroma compound in cv. Yinghong No. 9, were investigated. Linalool content was lower in albino-induced yellow leaves, which was due to the lower GDP content compared with normal green leaves.

Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

BACKGROUND: As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. RESULTS: The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. CONCLUSIONS: Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy.

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.

Human epidermal growth factor receptor-2 antibodies enhance the specificity and anticancer activity of light-sensitive doxorubicin-labeled liposomes.

Antibody-mediated targeting therapy has been successful in treating patients with cancers by improving the specificity and clinical efficacy. In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) light-sensitive liposomes containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated the specific binding and selective toxicity of the system to HER2-positive tumor cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2-antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor model in nude mice simultaneously bearing HER2-positive and -negative tumors. This induced a >2-fold increased accumulation in the tumors with positive expression of HER2 than that with non-targeted liposomes (no HER2-antibody conjugation). The combination of targeted liposomes with NIR laser irradiation had significant antitumor activity in vivo with the tumor inhibition efficiency up to 92.7%, attributed to the increased accumulation in tumors and the double efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause systemic toxicity during the experiment period, attributable to the reduced dose of DOX, the decreased accumulation of liposomes in normal tissues, and the low irradiation power. The targeted liposomes provide a multifunctional nanotechnology platform for antibody-mediated delivery, light-trigged drug release, and combined photothermal-chemotherapy, which may have potential in the clinical treatment of cancer.