Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling.

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries, including glaucoma, diabetic retinopathy, traumatic optic neuropathy and optic neuritis, etc. The current clinical treatment is not very effective. We investigated indirubin, one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill, in the present study for its role in retinal neurodegeneration. Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro. Moreover, indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo. Furthermore, indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro. In addition, indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress. Mechanically, indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling. In conclusion, indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury. The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

Boosting CO2 Electroreduction to C2H4 via Unconventional Hybridization: High-Order Ce4+ 4f and O 2p Interaction in Ce-Cu2O for Stabilizing Cu.

Efficient conversion of carbon dioxide (CO2) into value-added materials and feedstocks, powered by renewable electricity, presents a promising strategy to reduce greenhouse gas emissions and close the anthropogenic carbon loop. Recently, there has been intense interest in Cu2O-based catalysts for the CO2 reduction reaction (CO2RR), owing to their capabilities in enhancing C-C coupling. However, the electrochemical instability of Cu+ in Cu2O leads to its inevitable reduction to Cu0, resulting in poor selectivity for C2+ products. Herein, we propose an unconventional and feasible strategy for stabilizing Cu+ through the construction of a Ce4+ 4f-O 2p-Cu+ 3d network structure in Ce-Cu2O. Experimental results and theoretical calculations confirm that the unconventional orbital hybridization near Ef based on the high-order Ce4+ 4f and 2p can more effectively inhibit the leaching of lattice oxygen, thereby stabilizing Cu+ in Ce-Cu2O, compared with traditional d-p hybridization. Compared to pure Cu2O, the Ce-Cu2O catalyst increased the ratio of C2H4/CO by 1.69-fold during the CO2RR at -1.3 V. Furthermore, in situ and ex situ spectroscopic techniques were utilized to track the oxidation valency of copper under CO2RR conditions with time resolution, identifying the well-maintained Cu+ species in the Ce-Cu2O catalyst. This work not only presents an avenue to CO2RR catalyst design involving the high-order 4f and 2p orbital hybridization but also provides deep insights into the metal-oxidation-state-dependent selectivity of catalysts.

The Effects of Light Therapy for Depression in Dementia: A Systematic Review and Meta-Analysis.

BACKGROUND: Depression is one of the most common symptoms in patients with dementia. OBJECTIVE: This meta-analysis aimed to evaluate the effect of light therapy on depression associated with dementia by using a single scale. METHODS: Published studies based on the terms including "Dementia", "depression", and "Phototherapy" were searched. Web of Science, PubMed, Embase, CiNii, CNKI, Wanfang Database, and China Biology Medicine disc were adopted to collect randomized controlled studies or cross-controlled studies using the Cornell Scale for Depression in Dementia (CSDD) until February 2022. GRADE and Review Manager Version 5.4.1 were employed to assess the risk of bias. A meta-analysis was conducted by R 4.0.2 software based on the changes in CSDD scores. RESULTS: A total of 1,055 studies were retrieved from the databases, and six studies were included after screening. Some 406 people with dementia were included with an average age of over 80 years. Forest plot results showed that light intervention improved depression scores of dementia patients (MD = -2.59, 95% CI: -4.46 to -0.71), and light intensity less than 1,000 lux improved depression symptoms of dementia patients (MD = -2.76, 95% CI: -4.55 to -0.97). An intervention that lasted 8 to 12 weeks was the most effective (MD = -3.77, 95% CI: -6.93 to -0.60), and non-stable interventions such as ceiling LED lights exerted more positive effects (MD = -2.12, 95% CI: -3.38 to -0.85). CONCLUSION: The overall results of the meta-analysis suggested that light intervention can improve the depressive symptoms of older patients with dementia.

Novel pituitary actions of GnRH in teleost: The link between reproduction and feeding regulation.

Gonadotropin-releasing hormone (GnRH), as a vital hypothalamic neuropeptide, was a key regulator for pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the vertebrate. However, little is known about the other pituitary actions of GnRH in teleost. In the present study, two GnRH variants (namely, GnRH2 and GnRH3) and four GnRH receptors (namely, GnRHR1, GnRHR2, GnRHR3, and GnRHR4) had been isolated from grass carp. Tissue distribution displayed that GnRHR4 was more highly detected in the pituitary than the other three GnRHRs. Interestingly, ligand-receptor selectivity showed that GnRHR4 displayed a similar and high binding affinity for grass carp GnRH2 and GnRH3. Using primary culture grass carp pituitary cells as model, we found that both GnRH2 and GnRH3 could not only significantly induce pituitary reproductive hormone gene (GtHα, LHß, FSHß, INHBa, secretogranin-2) mRNA expression mediated by AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways but also reduce dopamine receptor 2 (DRD2) mRNA expression via the Ca2+/CaM/CaMK-II pathway. Interestingly, GnRH2 and GnRH3 could also stimulate anorexigenic peptide (POMCb, CART2, UTS1, NMBa, and NMBb) mRNA expression via AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways in grass carp pituitary cells. In addition, food intake could significantly induce brain GnRH2 mRNA expression. These results indicated that GnRH should be the coupling factor to integrate the feeding metabolism and reproduction in teleost.

Ginseng Prong Added to Broiler Diets Reduces Lipid Peroxidation in Refrigerated and Frozen Stored Poultry Meats.

Fatty acid content and lipid oxidation products were compared in chicken breast and leg meats derived from birds fed on animal-fat- and vegetable-oil-based diets, supplemented with ginseng prong powder. The first experiment examined polyunsaturated fatty acid (PUFA) content and the formation of primary and secondary lipid oxidation products in meats stored at refrigeration temperatures (4 °C) for up to 10 days, while the second experiment examined similar changes in the poultry meats when frozen stored at -18 °C, for up to six months. Results showed that initial lipid hydroperoxide concentrations increased in both breast and leg meat within the first week of refrigerated storage and also was ongoing during the first three to four months of frozen storage. A higher (p < 0.05) PUFA content in leg meat, especially in broilers fed a vegetable-oil-blended diet, corresponded to greater tendency for generation of primary lipid oxidation products after refrigerated and frozen storage (p < 0.05). The inclusion of powdered ginseng prong in broiler diets significantly inhibited (p < 0.05) secondary lipid oxidation products (e.g., malonaldehyde [MDA]) formation in both stored leg and breast meat, compared to controls. Significant interactions (p < 0.05) were obtained for storage time and inclusion of ginseng against production of primary and secondary lipid oxidation in broiler breast and leg meats from broilers fed PUFA-containing diets. We conclude that including ginseng prong in broiler growing diets represents a viable strategy to control lipid oxidation in refrigerated/cold-stored meat products.

Turmeric and its bioactive constituents trigger cell signaling mechanisms that protect against diabetes and cardiovascular diseases.

Turmeric, the rhizome of Curcuma longa plant belonging to the ginger family Zingiberaceae, has a history in Ayurvedic and traditional Chinese medicine for treatment of chronic diseases, including metabolic and cardiovascular diseases (CVD). This parallels a prevalence of age- and lifestyle-related diseases, especially CVD and type 2 diabetes (T2D), and associated mortality which has occurred in recent decades. While the chemical composition of turmeric is complex, curcuminoids and essential oils are known as two major groups that display bioactive properties. Curcumin, the most predominant curcuminoid, can modulate several cell signaling pathways involved in the etiology and pathogenesis of CVD, T2D, and related morbidities. Lesser bioactivities have been reported from other curcuminoids and essential oils. This review examines the chemical compositions of turmeric, and related bioactive constituents. A focus was placed on the cellular and molecular mechanisms that underlie the protective effects of turmeric and turmeric-derived compounds against diabetes and CVD, compiled from the findings obtained with cell-based and animal models. Evidence from clinical trials is also presented to identify potential preventative and therapeutic efficacies. Clinical studies with longer intervention durations and specific endpoints for assessing health outcomes are warranted in order to fully evaluate the long-term protective efficacy of turmeric.

Insight into the mechanism of low molecular weight organic acids-mediated release of phosphorus and potassium from biochars.

A crucial mechanism for the application of biochar in soil improvement is the direct release of nutrients from biochar. Low molecular weight organic acids (LMWOAs) ubiquitously exist in soil. However, the mechanism of LMWOAs-mediated release of nutrients from biochars remains little known. Ten biochars with different mineral element stoichiometric ratio were produced, and four LMWOAs [acetic (HAc), glycolic (GA), tartaric (TA), and citric acids (CA)] were employed, to enunciate the influence mechanism of LMWOAs on the release of phosphorus and potassium from biochar. The results showed that HAc suppressed the release of P from biochars, while TA and CA facilitated the release of P from biochars with high ratios of polyvalent metals to P. A new mechanism was proposed that the deprotonated HAc combined with the dissolved HPO42- or H2PO4- to form a complex through hydrogen bond and cation bridging. The hydrophobic methyl group of HAc was exposed outside of the complex, which decreased the water-solubility of phosphate. Meanwhile, a high ratio of polyvalent metals to P benefited more P to combine with polyvalent metals, which decreased the water-solubility of P, but the deprotonated TA and CA are polyvalent anions that could substitute this part of P by anion exchange. Also, LMWOAs promoted the release of K from biochars with low K/(P + S) ratios, possibly due to unionized carboxyl of LMWOAs served as a hydrogen bond donor to displace K out of biochars. This study gives a deep understanding of the fate of biochar originated nutrients response to LMWOAs.

Effect of Marine Microalga Chlorella pyrenoidosa Ethanol Extract on Lipid Metabolism and Gut Microbiota Composition in High-Fat Diet-Fed Rats.

Effects of marine microalga Chlorella pyrenoidosa 55% ethanol extract (CPE55) on lipid metabolism, gut microbiota and regulation mechanism in high fat diet-fed induced hyperlipidaemia rats were investigated. Structure characterizations of major compounds in CPE55 were determined by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The compositions of gut microbiota in rats were analyzed by high-throughput next-generation 16S rRNA gene sequencing. Oral administration with CPE55 markedly alleviated dyslipidemia through improving adverse blood lipid profile and inhibiting hepatic lipid accumulation and steatosis. CPE55 has downregulated the gene expression levels of acetyl CoA carboxylase, sterol regulatory element-binding transcription factor-1c, and 3-hydroxy-3-methyl glutaryl coenzyme A reductase and upregulated adenosine 5'-monophosphate-activated protein kinase-α. It has also improved the abundance of bacteria Alistipes, Prevotella, Alloprevotella, and Ruminococcus1 and decreased the abundances of Turicibacter and Lachnospira. Turicibacter and Lachnospira were both positive correlations of metabolic phenotypes. The findings above illustrated that CPE55 might be developed as food ingredients to ameliorate lipid metabolic disorders and hyperlipidaemia.

Promoter RNA links transcriptional regulation of inflammatory pathway genes.

Although many long non-coding RNAs (lncRNAs) have been discovered, their function and their association with RNAi factors in the nucleus have remained obscure. Here, we identify RNA transcripts that overlap the cyclooxygenase-2 (COX-2) promoter and contain two adjacent binding sites for an endogenous miRNA, miR-589. We find that miR-589 binds the promoter RNA and activates COX-2 transcription. In addition to miR-589, fully complementary duplex RNAs that target the COX-2 promoter transcript activate COX-2 transcription. Activation by small RNA requires RNAi factors argonaute-2 (AGO2) and GW182, but does not require AGO2-mediated cleavage of the promoter RNA. Instead, the promoter RNA functions as a scaffold. Binding of AGO2 protein/small RNA complexes to the promoter RNA triggers gene activation. Gene looping allows interactions between the promoters of COX-2 and phospholipase A2 (PLA2G4A), an adjacent pro-inflammatory pathway gene that produces arachidonic acid, the substrate for COX-2 protein. miR-589 and fully complementary small RNAs regulate both COX-2 and PLA2G4A gene expression, revealing an unexpected connection between key steps of the eicosanoid signaling pathway. The work demonstrates the potential for RNA to coordinate locus-dependent assembly of related genes to form functional operons through cis-looping.