Ferritinophagy-mediated apoptosis and paraptosis induction involved MAPK and PI3K/AKT pathway in mechanism of an iron chelator.

Melanoma cells were more resistant to ferroptosis with still poor therapy outcomes. Sensitizing melanoma cell to the ferroptosis inducer was a crucial strategy for treatment of melanoma. In the present study, 2,2'-di-pyridylketone hydrazone dithiocarbamate s-butyric acid (DpdtbA) displayed superior inhibitory activity than ferroptosis inducer Erastin in melanoma cells, which prompt us to explore the underlying mechanism. The analyses from flow cytometry and Western blot showed that the growth inhibition of DpdtbA against SK-MEL-28 and A375 cells involved apoptosis induction and G1 phase arrest. Surprisingly, the cytoplasmic vacuoles were found upon the treatment; transmission electron microscopy and endoplasmic reticulum (ER) staining revealed that the cytoplasmic vacuoles were in ER; while down-regulation of alix and requirement of protein synthesis suggested there was an occurrence of paraptosis. However, both NAC and 3-MA could significantly attenuate the cytoplasmic vacuolization and growth inhibition, hinting that both ROS and autophagy involved the paraptosis induction. The additional evidence revealed that there was an occurrence of continuous ferritinophagy, which was responsible for the ROS production. Downregulation of NCOA4 clearly attenuated the apoptosis and paraptosis induction. In addition, activation of MAPK involved regulation of paraptosis, but only ERK and JNK had role in the formation of cytoplasmic vacuoles and growth inhibition. Furthermore, a ROS dependent regulation of PI3K/AKT pathway was also involved. Taken together, our result firstly demonstrated that a continuous ferritinophagy contributed to the apoptosis and paraptosis induction, highlighting that the lysosomal labile iron pool had a crucial role in control of melanoma cell fate.

The detection of selectivity and sensitivity towards TNP by a new Zn(II)-coordination polymer as luminescent sensor in aqueous solution.

Nitroaromatic compounds (NACs) can lead to various environmental pollution healh problems. In order to effectively recognize and sense NACs, a novel coordination polymers (CPs) with fluorescent characteristic [Zn3(btc)2(tpt)(H2O)2]·4H2O (1) (tpt = tris(4-pyridyl)triazine, H3btc = 1,3,5-benzenetricarboxylic acid) has been triumphantly prepared as an fluorescence probe by solvothermal method. 1 possesses remarkable PH stability ranging from 2.0 to 12.0 and is also stable in different pure organic solvents. It should be noted that 1 manifests a fluorescence quenching response against the detection of selectivity and sensitivity towards 2,4,6-trinitrophenol (TNP) in aqueous solution. It also makes analysis on the limit of detection towards TNP, which is as low as 0.94 µM compared with most reported CPs sensors for TNP. Therefore, 1 can become a satisfactory sensor for TNP detection with remarkable selectivity, strong anti-interference and favorable recyclability. In addition, the quenching mechanisms were also discussed. It was supposed that the mechanisms of photoinduced electron transfer (PET) as well as resonance energy transfer (RET) might be the main influencing factors.

Transcriptome and Metabolome Comparison of Smooth and Rough Citrus limon L. Peels Grown on Same Trees and Harvested in Different Seasons.

Background: Farmers harvest two batches fruits of Lemons (Citrus limon L. Burm. f.) i.e., spring flowering fruit and autumn flowering fruit in dry-hot valley in Yunnan, China. Regular lemons harvested in autumn have smooth skin. However, lemons harvested in spring have rough skin, which makes them less attractive to customers. Furthermore, the rough skin causes a reduction in commodity value and economical losses to farmers. This is a preliminary study that investigates the key transcriptomic and metabolomic differences in peels of lemon fruits (variety Yuning no. 1) harvested 30, 60, 90, 120, and 150 days after flowering from the same trees in different seasons. Results: We identified 5,792, 4,001, 3,148, and 5,287 differentially expressed genes (DEGs) between smooth peel (C) and rough peel (D) 60, 90, 120, and 150 days after flowering, respectively. A total of 1,193 metabolites differentially accumulated (DAM) between D and C. The DEGs and DAMs were enriched in the mitogen-activated protein kinase (MAPK) and plant hormone signaling, terpenoid biosynthesis, flavonoid, and phenylalanine biosynthesis, and ribosome pathways. Predominantly, in the early stages, phytohormonal regulation and signaling were the main driving force for changes in peel surface. Changes in the expression of genes associated with asymmetric cell division were also an important observation. The biosynthesis of terpenoids was possibly reduced in rough peels, while the exclusive expression of cell wall synthesis-related genes could be a possible reason for the thick peel of the rough-skinned lemons. Additionally, cell division, cell number, hypocotyl growth, accumulation of fatty acids, lignans and coumarins- related gene expression, and metabolite accumulation changes were major observations. Conclusion: The rough peels fruit (autumn flowering fruit) and smooth peels fruit (spring flowering fruit) matured on the same trees are possibly due to the differential regulation of asymmetric cell division, cell number regulation, and randomization of hypocotyl growth related genes and the accumulation of terpenoids, flavonoids, fatty acids, lignans, and coumarins. The preliminary results of this study are important for increasing the understanding of peel roughness in lemon and other citrus species.

Variations of membrane fatty acids and epicuticular wax metabolism in response to oleocellosis in lemon fruit.

Oleocellosis is a physiological disorder causing blemishes on fruit surface. This study investigated the influence of oleocellosis on the membrane fatty acids and wax in lemon fruit rinds at the morphological, physiological, metabolic and molecular levels by using a variety with a high incidence rate of oleocellosis (green lemon). Oleocellosis-damaged rinds showed loose and flaky wax layers with more fissures on the surface, as well as higher contents of C16 and C18 fatty acids and very long chain (VLC) fatty alkanes while lower contents of VLC fatty aldehydes. The main differentially expressed genes, including FabZ, FAD2 and SAD6 involved in the accumulation of C16 and C18 fatty acids and CER1 involved in the transformation of VLC fatty aldehydes to VLC fatty alkanes, were up-regulated by oleocellosis. These results indicate that oleocellosis accelerates the accumulation of membrane free fatty acids and transformation of VLC fatty aldehydes to VLC fatty alkanes.

A luminescent Cd(II)-metal organic frameworks combined of TPT and H3BTC detecting 2,4,6-trinitrophenol and chromate anions in aqueous.

A new luminescence Cd(II)-MOF (1) ([Cd3(BTC)2(TPT)(H2O)2]·4H2O, TPT = tris(4-pyridyl)triazine, H3BTC = 1,3,5-benzenetricarboxylic acid) was successfully synthesized under solvothermal conditions. 1 contains 3D framework which consist of Cd atoms and btc3- anions with the large channels along c axis. Then, tpt ligands locate in the channels by utilizing three N atoms to bridge two Cd1 atoms and one Cd2 atom. 1 not only possesses remarkable thermal stability, but also can steadily exist in different organic solvents and various acid/base solutions (pH = 3-12). Moreover, 1 can detect 2,4,6-trinitrophenol (TNP) and chromate (CrO42-/Cr2O72-) anions with high selectivity and sensitivity in water via the luminescent quenching. The detection limits of 1 for TNP and CrO42-/Cr2O72- are 6.23 µM and 2.13 µM/2.87 µM. The mechanism of TNP luminescence quenching may be attributed to photoinduced electron transfer and resonance energy transfer, and CrO42-/Cr2O72- quenching involves resonance energy transfer and competitive absorption of light. Additionally, 1 has the great anti-interference ability and repeatability for detecting TNP and CrO42-/Cr2O72-, which can display the feasibility of this material as a stable luminescent probe in aqueous system.

Variations of Flavonoid Composition and Antioxidant Properties among Different Cultivars, Fruit Tissues and Developmental Stages of Citrus Fruits.

A large number of biologically active compounds are present in ripe citrus fruits. However, few studies have been focused on the changes in flavonoids and the evolution of antioxidant activity during citrus fruit growth. In this study, fruits of five citrus cultivars cultivated in China were sampled at 60-210 days post-anthesis (DPA) at intervals of 30 days. The amounts of main flavonoids in the peel and pulp were analyzed by HPLC and their activities were studied by DPPH, ABTS and FRAP. The results showed that the contents of hesperidin, diosmin, eriodictyol, rutin and nobiletin increased before 90 DPA and then decreased with the growth and development of fruits, but an opposite tendency was observed for naringin and narirutin. The antioxidant activities in citrus peel and pulp were found to be significantly correlated with some flavonoids. The results may be of guiding values in citrus production and utilization of citrus fruit by-products.

Effect of lemon water soluble extract on hyperuricemia in a mouse model.

Lemon is a healthy fruit with high medicinal value. This study found that lemon water soluble extract (LET) can reduce uric acid levels in mice with potassium oxonate induced hyperuricemia. Histopathological analysis suggested that LET caused little damage to the kidneys of mice. It affected mABCG2 and mGLUT9 mRNA expression only in hyperuricemic mice, but not in healthy mice. Our further results show that potassium citrate, rather than citric acid, is the main ingredient in LET with a hypouricemic effect. This study also indicates that lemon does have unique medicinal value for the treatment of hyperuricemia, and that potassium citrate has the potential to be developed as a drug for hyperuricemia. Lowering uric acid through LET and potassium citrate may directly promote the degradation of excessive uric acid in patients with hyperuricemia.

Identification of Genes Associated with Lemon Floral Transition and Flower Development during Floral Inductive Water Deficits: A Hypothetical Model.

Water deficit is a key factor to induce flowering in many woody plants, but reports on the molecular mechanisms of floral induction and flowering by water deficit are scarce. Here, we analyzed the morphology, cytology, and different hormone levels of lemon buds during floral inductive water deficits. Higher levels of ABA were observed, and the initiation of floral bud differentiation was examined by paraffin sections analysis. A total of 1638 differentially expressed genes (DEGs) were identified by RNA sequencing. DEGs were related to flowering, hormone biosynthesis, or metabolism. The expression of some DEGs was associated with floral induction by real-time PCR analysis. However, some DEGs may not have anything to do with flowering induction/flower development; they may be involved in general stress/drought response. Four genes from the phosphatidylethanolamine-binding protein family were further investigated. Ectopic expression of these genes in Arabidopsis changed the flowering time of transgenic plants. Furthermore, the 5' flanking region of these genes was also isolated and sequence analysis revealed the presence of several putative cis-regulatory elements, including basic elements and hormone regulation elements. The spatial and temporal expression patterns of these promoters were investigated under water deficit treatment. Based on these findings, we propose a model for citrus flowering under water deficit conditions, which will enable us to further understand the molecular mechanism of water deficit-regulated flowering in citrus. HIGHLIGHT: Based on gene activity during floral inductive water deficits identified by RNA sequencing and genes associated with lemon floral transition, a model for citrus flowering under water deficit conditions is proposed.

Complementary and Alternative Medicine for the Management of Cervical Radiculopathy: An Overview of Systematic Reviews.

Background. Complementary and alternative medicine (CAM) is widely applied in the clinical practice of neck pain owing to cervical radiculopathy (CR). While many systematic reviews exist in CAM to improve CR, research is distributed across population, intervention, comparison, and setting. Objective. This overview aims to summarize the characteristics and evaluate critically the evidence from systematic reviews. Methods. A comprehensive literature search was performed in the six databases without language restrictions on February 24, 2015. We had identified relevant systematic reviews that examined the subjects with neck pain due to cervical radiculopathy undergoing CAM. Two authors independently appraised the methodological quality using the revised assessment of multiple systematic reviews instrument. Results. We had included eight systematic reviews. The effectiveness and safety of acupotomy, acupuncture, Jingfukang granule, manual therapies, and cervical spine manipulation were investigated. Based on available evidence, the systematic reviews supported various forms of CAM for CR. Nevertheless, the methodological quality for most of systematic reviews was low or moderate. In addition, adverse reactions of primary studies were infrequent. Conclusions. Current systematic reviews showed potential advantages to CAM for CR. Due to the frequently poor methodological quality of primary studies, the conclusions should be treated with caution for clinical practice.

Is TENS purely a placebo effect? A controlled study on chronic low back pain.

Although high-frequency low-intensity transcutaneous electric nerve stimulation (TENS) has been extensively used to relieve low back pain, experimental studies of its effectiveness have yielded contradictory findings mainly due to methodological problems in pain evaluation and placebo control. In the present study, separate visual analog scales (VAS) were used to measure the sensory-discriminative and motivational-affective components of low back pain. Forty-two subjects were randomly assigned to 1 of 3 groups: TENS, placebo-TENS, and no treatment (control). In order to measure the short-term effect of TENS, VAS pain ratings were taken before and after each treatment session. Also, to measure long-term effects, patients rated their pain at home every 2 h throughout a 3-day period before and 1 week, 3 months and 6 months after the treatment sessions. In comparing the pain evaluations made immediately before and after each treatment session, TENS and placebo-TENS significantly reduced both the intensity and unpleasantness of chronic low back pain. TENS was significantly more efficient than placebo-TENS in reducing pain intensity but not pain unpleasantness. TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness. This additive effect was not found for placebo-TENS. When evaluated at home, pain intensity was significantly reduced more by TENS than placebo-TENS 1 week after the end of treatment, but not 3 months and 6 months later. At home evaluation of pain unpleasantness in the TENS group was never different from the placebo-TENS group.(ABSTRACT TRUNCATED AT 250 WORDS)