Bid, a BH3-only Bcl-2 family member, is proven to be a pivotal molecule for the regulation of tumorigenesis by its multiple functions in promoting apoptosis, survival and proliferation. Growing evidence supports that Bid has double roles with respect to stress-response. In most cases it functions in a truncated form, but the cleavage of Bid may not be an absolute requirement for Bid to be pro-apoptotic. Full-length Bid can also translocate to and activate the mitochondria without cleavage. Bid has emerged as a central player linking death signals through surface death receptors to the core apoptotic mitochondrial pathway. Bid is also involved in DNA damage response, and the phosphorylated Bid may negatively regulate its pro-apoptotic function independent of the BH3 domain. This review surveys recent developments in understanding the molecular mechanisms of Bid activation and its roles in regulating the cross-talk of cell cycle arrest and apoptosis.

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Purpose The aim of this study was to observe the mechanism of Fructus Lycii (FL), Rehmanniae Radix Praeparata (RRP) and Paeonia lactiflora (PL) in treating age-related macular degeneration (AMD) based on network pharmacology and biological experiments. Methods Bioactive compounds, potential targets of FL, RRP and PL, and genes related to AMD, were acquired from public databases. Functional and pathway enrichment analyses of the core targets were conducted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the finding was further verified with cell experiments. The MTT assay and flow cytometric analysis were used to assess cell viability and apoptosis. The production of reactive oxygen species (ROS) was analyzed by DCFH-DA staining; the activity of antioxidant enzymes was chemically measured with assay kits. The expression of key proteins was evaluated by Western blot analysis. Results Fifty-nine active compounds, 182 potential targets, and 2536 AMD-related human genes were identified. A total of 103 key targets of the three herbs on AMD were identified by protein–protein interaction (PPI) analysis. The abovementioned targets were correlated with nuclear receptor activity, oxidative stress, and apoptosis pathways according to the GO and KEGG analyses. MTT assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with the three herbs significantly increased cell viability and decreased apoptosis induced by H 2 O 2 . The three herbs might reduce the intracellular ROS levels and increase the SOD and CAT activities after H 2 O 2 . Furthermore, the three herbs significantly inhibited oxidative stress via increasing the expression of Nrf2, HO-1 and NQO1. Conclusion The combined results of network pharmacology and validation experiments showed that FL, RRP and PL reduce oxidative stress and apoptosis in RPE cells to exert its effect in the treatment of AMD.

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Background: To compare the efficacy of one initial intravitreal injection of conbercept (IVC) versus three monthly IVCs in patients with macular edema (ME) after branch retinal vein occlusion (BRVO). Both options were followed by a pro re nata (PRN) retreatment regimen. Methods: This study retrospectively investigated and followed 60 patients with acute ME secondary to BRVO for over a year. 30 subjects received one initial injection (1 + PRN group); while, 30 received three monthly injections (3 + PRN group). The functional and anatomic outcomes were assessed during each follow-up. Results: The general characteristics of the 60 subjects were as follows: mean [SD] age, 57.43 [13.06] years; 33 [55%] female; 36 [60%] non-ischemic form. Both groups showed a stable gain in visual acuity (VA) with similar logMAR (mean ± SD) (1 + PRN group 0.308 ± 0.399, 3 + PRN group 0.34 ± 0.352) during the first 12 months. Additionally, both groups exhibited a significant reduction in central foveal thickness (CFT) with no statistically significant difference between them (1 + PRN group 222.1 μm ± 197.1 μm, 3 + PRN group 228.4 μm ± 200.2 μm). Both treatment groups had similar improvements in logMAR and anatomic outcomes over time. The stratified analysis showed that patients with the non-ischemic form and those with the ischemic form had similar improvements in VA (0.346 ± 0.366 VS 0.29 ± 0.39, P = 0.575) during the 12 months follow-ups. The number of injections was lower in the 1 + PRN group (4.0 ± 1.6) than in the 3 + PRN group (4.7 ± 1.3) (P = 0.068). No adverse effects or unexpected safety issues were reported in either group. Conclusions: Conbercept yielded significant improvements in VA and CFT among patients with BRVO induced ME, independent of their retinal ischemia status. The results showed that the 3 + PRN regimen do not lead to better functional outcomes or lower treatment needs in clinical practice as compared to the 1 + PRN regimen.

Oxidative stress and diminished autophagy in the retinal pigment epithelium (RPE) play crucial roles in the pathogenesis of age-related macular degeneration (AMD). Enhancing autophagy has recently been identified as an important strategy to protect RPE cells from oxidative damage. Ming-Mu-Di-Huang-Pill (MMDH pill) is a traditional herbal medicine used to treat AMD, and its molecular mechanism is not well understood. The aim of the present study was to investigate whether the MMDH pill relieved acute oxidative damage by activating autophagy in an in vitro and in vivo model of sodium iodate (NaIO3). The results showed that NaIO3 induced cell death and inhibited proliferation. The MMDH pill increased cell viability, restored the activities of antioxidant enzymes, and reduced reactive oxygen species (ROS) fluorescence intensity. The MMDH pill mediated Kelch-like ECH-associated protein 1 (Keap1) degradation and decreased oxidative damage, which was blocked in autophagy inhibitor (chloroquine) or sequestosome-1 (SQSTM1) siRNA-treated RPE cells. Furthermore, we indicated that the MMDH pill could promote adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and autophagy adaptor-SQSTM1 expression, which could stimulate autophagic degradation of Keap1. In addition, the MMDH pill increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation in a SQSTM1-dependent manner and induced the expression of the downstream antioxidant factors heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1). In conclusion, MMDH pill plays a protective role in relieving NaIO3-induced oxidative stress by activating the AMPK/SQSTM1/Keap1 pathway. The MMDH pill may be useful to treat AMD by maintaining redox homeostasis and autophagy.

Objective To compare the efficacy of one initial intravitreal injection of conbercept (IVC) versus three monthly IVCs in patients with macular edema (ME) after branch retinal vein occlusion (BRVO). Both options were followed by a pro re nata (PRN) retreatment regimen.Methods This study retrospectively investigated and followed 49 patients with acute ME secondary to BRVO for over a year. 24 subjects received one initial injection (1+PRN group); while, 25 received three monthly injections (3+PRN group). The functional and anatomic outcomes were assessed during each follow-up.Results The general characteristics of the 49 subjects were as follows: mean [SD] age, 56.12 [12.54] years; 28 [57.1%] female; 30 [61.2%] non-ischemic form. Both groups showed a stable gain in visual acuity (VA) with similar logMAR (mean ± SD) (1+PRN group 0.308±0.431, 3+PRN group 0.345±0.366) during the first 12 months. Additionally, both groups exhibited a significant reduction in central foveal thickness (CFT) with no statistically significant difference between them (1+PRN group 220.5 μm ±219.9 μm , 3+PRN group 230.2 μm ±220 μm ). Both treatment groups had similar improvements in logMAR and anatomic outcomes over time. The stratified analysis showed that patients with the non-ischemic form and those with the ischemic form had similar improvements in VA (0.351±0.387 VS 0.289±0.417, P =0.601) during the 12 months follow-ups. The number of injections was lower in the 1+PRN group (4.0±1.7) than in the 3+PRN group (4.6±1.2) ( P =0.155). No adverse effects or unexpected safety issues were reported in either group.Conclusions Conpercept yielded stronger improvements in VA and CFT among patients with BRVO induced ME，independent of their retinal ischemia status. The results showed that the 3+PRN regimens do not lead to better functional outcomes or lower treatment needs in clinical practice as compared to the 1+PRN regimen.

Background Symbiotic nitrogen fixation in legumes is an important source of nitrogen supply in sustainable agriculture. Salinity is a key abiotic stress that negatively affects host plant growth, rhizobium-legume symbiosis and nitrogen fixation.Results To explore how the symbiotic relation impacts plant response to salinity, we assayed the proteome profile of alfalfa plants with active nodules (NA), inactive nodules (NI) or without nodules (NN) when plants were subjected to salinity stress. Our data suggested that NA plants respond to salinity stress through some unique signaling regulations. NA plants showed an upregulation of proteins related to cell wall remodeling and reactive oxygen species (ROS) scavenging and a down-regulation of proteins involved in protein synthesis and degradation. The data also showed that NA plants, together with NI plants, upregulated proteins in photosynthesis, carbon fixation and respiration, anion transport, and plant defense to pathogens.Conclusions The data suggest that the symbiotic relations conferred the host plant a better capacity to adjust the key processes, probably to more efficiently use energy and resources, deal with oxidative stress, and maintain ion homeostasis and healthy status during salinity stress.