Accumulation Of Proteins Research Articles

Spraying KH2PO4 Alleviates the Damage of Spring Low-Temperature Stress by Improving the Physiological Characteristics of Wheat Flag Leaves

The low-temperature stress (LTS) in spring results in tremendous yield loss in wheat production, and the application of potassium dihydrogen phosphate (KH2PO4) can alleviate stress-induced damage. However, the underlying effect of spraying KH2PO4 on the physiological characteristics of wheat flag leaves under spring LTS remains unclear. In this study, we investigated the effect of spraying KH2PO4 on flag leaf physiological traits and yield under spring LTS, including treatments at 15 °C and spraying H2O (CK), treatment at −4 °C and spraying H2O (LT1), and treatment at −4 °C and spraying KH2PO4 (LT2). The results showed that spraying KH2PO4 significantly increased the activities of the superoxide dismutase (SOD), the peroxidase (POD), and the catalase (CAT), and reduced malondialdehyde (MDA) content in the flag leaves. Compared to LT1, the SOD, POD, and CAT activities in the flag leaves of the Yangnong19 (YN19) and Xinmai26 (XM26) via LT2 increased by 5.5%, 10.9%, and 3.9%, and 5.4%, 9.2%, and 4.4%, respectively, and the MDA content of the YN19 and XM26 decreased by 10.5% and 9.1%, respectively, at 0–12 d after low temperature treatment (DALTT). Spraying KH2PO4 appreciably alleviated damage to the leaf cell morphology and tissue integrity, and increased the accumulation of proline and soluble protein, the chlorophyll content, and the activities of Ribulose–1,5–bisphosphate carboxylase and phosphoenolpyruvate carboxykinase. The net photosynthetic rate in the flag leaves of the YN19 and XM26 via LT2 increased by 37.9% and 35.9%, respectively, at 0–12 DALTT, compared to LT1. Moreover, spraying KH2PO4 reduced the yield loss rate of the YN19 and XM26 by 13.06% and 16.72%, respectively. The present study demonstrates that spraying KH2PO4 can enhance wheat resistance to spring LTS and maintain the photosynthetic capacity of flag leaves, alleviating the negative effects of LTS on grain yield.

Role of autophagy in myocardial remodeling after myocardial infarction.

Autophagy is the process of reusing the body's senescent and damaged cell components, which can be regarded as the cellular circulatory system. There are three distinct forms of autophagy: macro-autophagy, micro-autophagy, and chaperone-mediated autophagy. In the heart, autophagy is regulated mainly through mitophagy due to the metabolic changes of cardiomyocytes caused by ischemia and hypoxia. Myocardial remodeling is characterized by gradual heart enlargement, cardiac dysfunction, and extraordinary molecular changes. Cardiac remodeling after myocardial infarction is almost inevitable, which is the leading cause of heart failure. Autophagy has a protective effect on myocardial remodeling improvement. Autophagy can minimize cardiac remodeling by preventing misfolded protein accumulation and oxidative stress. This review summarizes the nestest molecular mechanisms of autophagy and myocardial remodeling, the protective effects, and the new target of autophagy medicine in cardiac remodeling. The future development and challenges of autophagy in heart disease are also summarized.

Sleep Disorders in Alzheimer’s Disease

Alzheimer’s disease is the leading cause of dementia worldwide. Patients typically exhibit cognitive impairment, memory loss, diminished social and occupational functioning, as well as language and motor disorders. Alzheimer’s disease is characterized by the abnormal accumulation of amyloid-β (Aβ) and phosphorylated tau in the brain. These pathological changes not only disrupt neuronal function and lead to cognitive deficits, but also interfere with sleep regulation, resulting in sleep disorders. Such disturbances can diminish nighttime sleep quality and contribute to daytime functional impairments, further exacerbating cognitive decline. Therefore, exploring the interplay between cognitive impairment, Alzheimer’s disease, and sleep disorders is crucial for enhancing the quality of life of Alzheimer’s patients. This review summarizes current literature on the interconnections among Alzheimer’s disease, cognitive impairment, and sleep disorders. Sleep disturbances are prevalent in Alzheimer’s patients and can also occur in those with amnestic mild cognitive impairment, which often precedes Alzheimer’s onset. Such sleep disorders may promote and accelerate the accumulation of amyloid-β and tau proteins [1-3]. Furthermore, Alzheimer’s patients may be more vulnerable to sleep disturbances, creating a potential vicious cycle. Further investigation into these relationships may provide valuable insights for the treatment or prevention of Alzheimer’s disease.

Juvenile-related tolerance to papaya sticky disease (PSD): proteomic, ultrastructural, and physiological events.

The proteomic analysis of PMeV-complex-infected C. papaya unveiled proteins undergoing modulation during the plant's development. The infection notably impacted processes related to photosynthesis and cell wall dynamics. The development of Papaya Sticky Disease (PSD), caused by the papaya meleira virus complex (PMeV-complex), occurs only after the juvenile/adult transition of Carica papaya plants, indicating the presence of tolerance mechanisms during the juvenile development phase. In this study, we quantified 1609 leaf proteins of C. papaya using a label-free strategy. A total of 345 differentially accumulated proteins were identified-38 at 3months (juvenile), 130 at 4months (juvenile/adult transition), 160 at 7months (fruit development), and 17 at 9months (fruit harvesting)-indicating modulation of biological processes at each developmental phase, primarily related to photosynthesis and cell wall remodeling. Infected 3- and 4-mpg C. papaya exhibited an accumulation of photosynthetic proteins, and chlorophyll fluorescence results suggested enhanced energy flux efficiency in photosystems II and I in these plants. Additionally, 3 and 4-mpg plants showed a reduction in cell wall-degrading enzymes, followed by an accumulation of proteins involved in the synthesis of wall precursors during the 7 and 9-mpg phases. These findings, along with ultrastructural data on laticifers, indicate that C. papaya struggles to maintain the integrity of laticifer walls, ultimately failing to do so after the 4-mpg phase, leading to latex exudation. This supports initiatives for the genetic improvement of C. papaya to enhance resistance against the PMeV-complex.

Impairment of spinal CSF flow precedes immune cell infiltration in an active EAE model

Accumulation of immune cells and proteins in the subarachnoid space (SAS) is found during multiple sclerosis and in the animal model experimental autoimmune encephalomyelitis (EAE). Whether the flow of cerebrospinal fluid (CSF) along the SAS of the spinal cord is impacted is yet unknown. Combining intravital near-infrared (NIR) imaging with histopathological analyses, we observed a significantly impaired bulk flow of CSF tracers within the SAS of the spinal cord prior to EAE onset, which persisted until peak stage and was only partially recovered during chronic disease. The impairment of spinal CSF flow coincided with the appearance of fibrin aggregates in the SAS, however, it preceded immune cell infiltration and breakdown of the glia limitans superficialis. Conversely, cranial CSF efflux to cervical lymph nodes was not altered during the disease course. Our study highlights an early and persistent impairment of spinal CSF flow and suggests it as a sensitive imaging biomarker for pathological changes within the leptomeninges.

HIV Protein Nef Induces Cardiomyopathy Through Induction of Bcl2 and p21

HIV-associated cardiovascular diseases remain a leading cause of death in people living with HIV/AIDS (PLWHA). Although antiretroviral drugs suppress the viral load, they fail to remove the virus entirely. HIV-1 Nef protein is known to play a role in viral virulence and HIV latency. Expression of Nef protein can be detected in different organs, including cardiac tissue. Despite the established role of Nef protein in HIV-1 replication, its impact on organ function inside the human body is not clear. To understand the effect of Nef at the organ level, we created a new Nef-transgenic (Nef-TG) mouse that expresses Nef protein in the heart. Our study found that Nef expression caused inhibition of cardiac function and pathological changes in the heart with increased fibrosis, leading to heart failure and early mortality. Further, we found that cellular autophagy is significantly inhibited in the cardiac tissue of Nef-TG mice. Mechanistically, we found that Nef protein causes the accumulation of Bcl2 and Beclin-1 proteins in the tissue, which may affect the cellular autophagy system. Additionally, we found Nef expression causes upregulation of the cellular senescence marker p21 and senescence-associated b-galactosidase expression. Our findings suggest that the Nef-mediated inhibition of autophagy and induction of senescence markers may promote aging in PLWHA. Our mouse model could help us to understand the effect of Nef protein on organ function during latent HIV infection.

NpCIPK6–NpSnRK1 module facilitates inter-subgeneric hybridization barriers in water lily (nymphaea) by reducing abscisic acid content

Abstract Pre-fertilization hybridization barriers are the main causes of inter-subgeneric hybridization challenges in water lily. However, the mechanism underlying low compatibility between pollen and stigma of water lily remains unclear. This study demonstrates that CBL-interacting protein kinase 6 (CIPK6) responded to the signaling exchange between incompatible pollen and stigma through interactions with SNF1-related kinase 1 (SnRK1) and promotes the accumulation of SnRK1 protein. Activated SnRK1 interacted with 9-cis-epoxycarotenoid dioxygenase 2 (NCED2) to promote its degradation, thereby inhibiting abscisic acid (ABA) synthesis. A decrease in ABA content in the stigma impaired the ABA-mediated removal of reactive oxygen species (ROS), ultimately resulting in the rejection of the incompatible pollen by the stigma. Our results highlight the essential role of the NpCIPK6–NpSnRK1–NpNCED2 module in conferring inter-subgeneric hybridization barriers in water lily by interfering with ABA synthesis and promoting ROS accumulation. This study offers valuable mechanistic insights into cellular signaling and reproductive barriers in water lily as well as across other biological contexts.

Manifestation of selection traits and properties of forage productivity in groups of alfalfa varieties with different resistance to viral and phytoplasma infections

The research was conducted in 2019–2023 in Belgorod region with the purpose of breeding evaluation of alfalfa cultivars with different resistance to «witches’ broom alfalfa» (WBA). Fifty-two selection samples belonging to species Medicago sativa L., M. varia Mart., M. falcata L. The soil is typical chernozem, humus content (according to Tyurin) 4.7…5.0 %, The year of sowing – 2019. Predecessor – pure fallow. Plots – two-row long 3.5 m, row spacing width – 0.3 m. Repetition – five times. Standard – variety Belgorodskaya 86, sown through 5 numbers. Seeding rate of 100 germinated seeds per 1 linear meter. It was found that the group of varietal samples (n = 10) with low resistance to WBA (variation of prevalence 24.3–34.9 %) is characterized by a greater accumulation of protein (by 44.6 g/kg, t = 8.0, p 0.05), higher foliage (by 4.8 %, t = 3.7, p 0.05) and height (by 25.3 cm, t = 6.2, p 0.05), compared to the group of varieties resistant to WBA (n = 12) (prevalence variation 4.6… 9.1 %). Varieties with high resistance to WBA, belong to yellow and yellow-hybrid alfalfa varieties: Pavlovskaya 7, PO-172, Marusinskaya 425, PO-173, Sarga, PO-174, Victoria, 20–89 H, 193–95d, PO-175, SGPR-8, Vela×Sarga. Varieties with low resistance to VML belong to blue alfalfa and partially – blue-hybrid varieties: Krasnoyaruzhskaya 2, SI-139, SI-138, Plateau, Verko, Luzelle, Salsa, Kreno, Galaxi, Planet.

A meta-analysis of the impact of water-solved pollutants on the protein content of Pistia stratiotes L.

Due to the high cost of conventional water cleaning procedures, an affordable alternative for developing countries is the use of Pistia stratiotes L. Although these plants adsorb toxic chemicals in their tissues, other studies report a high protein content in its biomass and propose to use it as a fodder or even for human consumption. Therefore, this study aimed to identify the impact of water-solved pollutants on the content of protein in the tissues of P. stratiotes through a meta-analysis of currently available literature. Scientific reports, which included the biochemical analysis of the species when exposed to pollutants in the growing media were retrieved. The statistical analysis identified that chromium, wastewater sludge from a sugar factory, fluoride and linear alkyl benzene sulphonate reduce the content of protein. On the contrary, metals such as copper and zinc showed a slight tendency to promote the accumulation of protein in the biomass. Only the use of municipal wastewater sludge consistently promoted the increase of protein. Since most pollutants reduced the protein content and others also pose a bioaccumulation risk, P. stratiotes is not recommended to be considered as a fodder or to be included in human diet without previously ensuring its chemical innocuity.

The neuropharmacological and clinical effects of lutein: a systematic review.

Neurodegenerative diseases are defined by specific protein accumulation and anatomic vulnerability leading to neuronal loss. Some studies have shown that lutein may have an effect on neurodegenerative diseases. As most of the neurodegenerative diseases don't have certain cure and therapies focus on symptom control, Lutein may be a complementary treatment. Due to controversies in studies investigating lutein effect on neurodegenerative diseases, we decided to perform a systematic review on these studies. A systematic search was carried out in the available databases. We used all MeSH terms and relevant keywords. Studies that reported relationship between lutein and any neurodegenerative disease were included. We found 278 studies. After removing duplicates, screening by titles and abstracts and excluding irrelevant papers, 17 articles were included in this study. Fourteen studies investigated Alzheimer's disease, 2 studies Parkinson's disease and 1 study Amyotrophic lateral sclerosis. 1/17 study found that high serum levels of lutein at baseline were associated with a lower risk of AD mortality and lutein effect on lipid profile have been investigated in 2/17 studies. Also, 1/17 study has been shown that high intake of lutein may reduce the risk of ALS progression. 4/17 studies confirm that lutein can improve cognitive function. 8/17 studies demonstrate a reduction inthe progression of AD, and 2/17 studies indicate an improvement in lipid profiles. However, some studies did not find any significant associations. Additionally, there is a limited number of studies investigating the effects of lutein on other neurodegenerative diseases.

Genotypic difference in green stem disorder severity and vegetative storage protein accumulation affected by different degrees of sink limitation in soybeans [Glycine max (L.) merr.]

ABSTRACT Green stem disorder (GSD) delays leaf and stem senescence even after pods mature in soybean. In this study, the relationship between GSD severity and vegetative storage protein (VSP) dynamics was investigated under different timings and intensities of depodding treatments. Short growth period (Yukihomare, Yu), GSD-susceptible (Tachinagaha, Tc), and GSD-resistant (Touhoku 129, Th) cultivars were grown under repeated depodding treatments from the R3 growth stage by half [R3 (1/2)] or by one-third [R3 (1/3)], under a single-time depodding treatment at the R5 growth stage by half [R5 (single)], and under no depodding (control). Depodding from R3 decreased the pod number and induced GSD for both Yu and Th. However, the pod weight and stem weight per plant were statistically unchanged from those in control, indicating that remaining pods partially served as a surplus source reservoir in Yu and Th. Tc reduced the pod number and pod weight and unchanged the stem weight in depodding treatments from R3 but induced GSD regardless of the treatments. The growth of single-time depodding at R5 was not different from that of control except the growth parameters of Yu. The relative VSP content temporarily increased 14 days after R3 (DAR3) in all the treatments and cultivars. Although the relative VSP content decreased afterward in Yu and Th, that of Tc increased according to the depodding intensity. In the depodding experiments over three years, a negative correlation tended to be found after 28 DAR3 between VSP accumulation and GSD severity in Th but not in Tc, suggesting that the mechanism underlying N metabolism and GSD occurrence was different between cultivars.

PRRSV non-structural protein 5 inhibits antiviral innate immunity by degrading multiple proteins of RLR signaling pathway through FAM134B-mediated ER-phagy.

Viruses employ various evasion strategies to establish prolonged infection, with evasion of innate immunity being particularly crucial. Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant pathogen in swine industry, characterized by reproductive failures in sows and respiratory distress in pigs of all ages, leading to substantial economic losses globally. In this study, we found that the non-structural protein 5 (Nsp5) of PRRSV antagonizes innate immune responses via inhibiting the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs), which is achieved by degrading multiple proteins of RIG-I-like receptor (RLR) signaling pathway (RIG-I, MDA5, MAVS, TBK1, IRF3, and IRF7). Furthermore, we showed that PRRSV Nsp5 is located in endoplasmic reticulum (ER), where it promotes accumulation of RLR signaling pathway proteins. Further data demonstrated that Nsp5 activates reticulophagy (ER-phagy), which is responsible for the degradation of RLR signaling pathway proteins and IFN-I production. Mechanistically, Nsp5 interacts with one of the ER-phagy receptor family with sequence similarity 134 member B (FAM134B), promoting the oligomerization of FAM134B. These findings elucidate a novel mechanism by which PRRSV utilizes FAM134B-mediated ER-phagy to elude host antiviral immunity.IMPORTANCEInnate immunity is the first line of host defense against viral infections. Therefore, viruses developed numerous mechanisms to evade the host innate immune responses for their own benefit. PRRSV, one of the most important endemic swine viruses, poses a significant threat to the swine industry worldwide. Here, we demonstrate for the first time that PRRSV utilizes its non-structural protein Nsp5 to degrade multiple proteins of RLR signaling pathways, which play important roles in IFN-I production. Moreover, FAM134B-mediated ER-phagy was further proved to be responsible for the protein's degradation. Our study highlights the critical role of ER-phagy in immune evasion of PRRSV to favor replication and provides new insights into the prevention and control of PRRSV.

Ribosomal S6 kinase (RSK) plays a critical role in DNA damage response via the phosphorylation of histone lysine demethylase KDM4B

BackgroundEpigenetic dysregulation affecting oncogenic transcription and DNA damage response is a hallmark of cancer. The histone demethylase KDM4B, a factor regulating these processes, plays important roles in estrogen receptor-mediated transcription and DNA repair in breast cancer. However, how oncogenic phospho-signal transduction affects epigenetic regulation is not fully understood. Here we found that KDM4B phosphorylation by ribosomal S6 kinase (RSK), a downstream effector of the Ras/MAPK pathway, is critical for the function of KDM4B in response to DNA damage.MethodsKDM4B-knockout breast cancer cell lines were generated via CRISPR/Cas9-mediated gene editing. Re-expression of wild-type or phospho-site mutated KDM4B in knockout cells was performed by lentivirus-mediated gene transfer. Gene knockdown was achieved by RNA interference. DNA double-strand breaks (DSBs) were induced by ionizing radiation or laser-microirradiation. Protein accumulation at DSB sites was analyzed by immunofluorescence. KDM4B phosphorylation by RSK was assessed by in vitro and in vivo kinase assays. Gene and protein expression levels were analyzed by RT‒PCR and western blotting. The sensitivity of cells to ionizing radiation was examined by a clonogenic survival assay.ResultsRSK phosphorylated KDM4B at Ser666, and inhibition of the phosphorylation by RSK depletion or RSK inhibitors abrogated KDM4B accumulation at the sites of DNA double-strand breaks (DSBs). DSB repair was significantly delayed in KDM4B-knockout cells or cells treated with RSK inhibitors. The replacement of endogenous KDM4B with the phosphomimetic mutant S666D restored KDM4B accumulation and DSB repair that had been inhibited by RSK inhibitors, suggesting a critical role for RSK at the specific serine residue of KDM4B in the effect of RSK inhibitors on DSB repair. As a consequence of these aberrant responses, inhibition of KDM4B phosphorylation increased the sensitivity of the cells to ionizing radiation.ConclusionsOverall, the present study uncovered a novel function of RSK on the DNA damage response, which provides an additional role of its inhibitor in cancer therapy.

Small peptide SiDVL/RTFLs from foxtail millet inhibit root growth through repressing auxin signaling in transgenic Arabidopsis.

SiDVLs inhibit auxin signaling to regulate root growth by enhancing the expression of Aux/IAAs and reducing the protein accumulation of PINs. The DEVIL/ ROTUNDIFOLIA (DVL/RTFL), a small polypeptide family, is conserved in seed plants and important in regulating plant growth and development. However, the molecular mechanisms remain largely unknown. Here, 27 SiDVLs were identified in foxtail millet genome. Overexpression of three SiDVLs in Arabidopsis (Arabidopsis thaliana) strongly repressed the plant growth, especially the root growth. We demonstrate that overexpression of SiDVLs enhances Auxin/Indole-3-Acetic Acids (Aux/IAAs) transcription, thereby weakening auxin signaling in the roots. Furthermore, SiDVLs reduced the protein levels of the auxin transporters PIN-formed 1 (PIN1), PIN2, and PIN7 in the roots. The impaired auxin signaling reduces the cell division and elongation. In conclusion, SiDVLs suppress cell division and elongation in root by inhibiting auxin signaling and transport, which lead to the reduced root growth.

Conditional Pten inactivation in pituitary results in sex-specific prolactinoma formation

Pituitary tumors, including prolactinomas, present significant clinical challenges that require a deeper understanding of their molecular roots for improved diagnostics and therapies. Here, we investigate the role of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K) pathway in pituitary tumorigenesis using a mouse model. Conditional knockout of Pten in all pituitary cell lineages resulted in prolactinoma formation exclusively in female mice, demonstrating the critical role of PTEN in pituitary homeostasis. While Pten inactivation induced Akt activation in all pituitary cells, only prolactin-producing cells exhibited tumorigenic changes, suggesting specific cell-type effects. Histological and molecular analyses of prolactinomas revealed similarities with human pituitary tumors, such as decreased vascularization and cell adhesion proteins and increased accumulation of cell cycle proteins. Notably, prolactinomas displayed diminished levels of phosphorylated extracellular signal-regulated kinase (ERK), implicating downregulation of ERK in tumorigenesis. Finally, we analyzed PTEN/PI3K activation in a collection of human pituitary tumors. Overall, our study delineates the intricate interplay between the PTEN and ERK signaling pathways, providing insights into sex-specific mechanisms of pituitary tumorigenesis and potential therapeutic strategies for prolactinomas.

Targeting Protein Aggregation in ALS.

Proteinopathies involve the abnormal accumulation of specific proteins. Maintaining the balance of the proteome is a finely regulated process managed by a complex network of cellular machinery responsible for protein synthesis, folding, and degradation. However, stress and ageing can disrupt this balance, leading to widespread protein aggregation. Currently, several therapies targeting protein aggregation are in clinical trials for ALS. These approaches mainly focus on two strategies: addressing proteins that are prone to aggregation due to mutations and targeting the cellular mechanisms that maintain protein homeostasis to prevent aggregation. This review will cover these emerging drugs. Advances in ALS research not only offer hope for better outcomes for ALS patients but also provide valuable insights and methodologies that can benefit the broader field of neurodegenerative disease drug discovery.

Metabolic pathways regulated by strigolactones foliar spraying enhance osmoregulation and antioxidant defense in drought-prone soybean

BackgroundDrought stress is a significant abiotic stressor that hinders growth, development, and crop yield in soybeans. Strigolactones (SLs) positively regulate plant resistance to drought stress. However, the impact of foliar application of SLs having different concentrations on soybean growth and metabolic pathways related to osmoregulation remains unknown. Therefore, to clarify the impact of SLs on soybean root growth and cellular osmoregulation under drought stress, we initially identified optimal concentrations and assessed key leaf and root indices. Furthermore, we conducted transcriptomic and metabolic analyses to identify differential metabolites and up-regulated genes.ResultsThe results demonstrated that drought stress had a significant impact on soybean biomass, root length, root surface area, water content and photosynthetic parameters. However, when SLs were applied through foliar application at appropriate concentrations, the accumulation of ABA and soluble protein increased, which enhanced drought tolerance of soybean seedlings by regulating osmotic balance, protecting membrane integrity, photosynthesis and activating ROS scavenging system. This also led to an increase in soybean root length, lateral root number and root surface area. Furthermore, the effects of different concentrations of SLs on soybean leaves and roots were found to be time-sensitive. However, the application of 0.5 µM SLs had the greatest beneficial impact on soybean growth and root morphogenesis under drought stress. A total of 368 differential metabolites were screened in drought and drought plus SLs treatments. The up-regulated genes were mainly involved in nitrogen compound utilization, and the down-regulated metabolic pathways were mainly involved in maintaining cellular osmoregulation and antioxidant defenses.ConclusionsSLs enhance osmoregulation in soybean plants under drought stress by regulating key metabolic pathways including Arachidonic acid metabolism, Glycerophospholipid metabolism, Linoleic acid metabolism, and Flavone and flavonol biosynthesis. This study contributes to the theoretical understanding of improving soybean adaptability and survival in response to drought stress.

Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction

The ability to derive retinal ganglion cells (RGCs) from human pluripotent stem cells (hPSCs) has led to numerous advances in the field of retinal research, with great potential for the use of hPSC-derived RGCs for studies of human retinal development, in vitro disease modeling, drug discovery, as well as their potential use for cell replacement therapeutics. Of all these possibilities, the use of hPSC-derived RGCs as a human-relevant platform for in vitro disease modeling has received the greatest attention, due to the translational relevance as well as the immediacy with which results may be obtained compared to more complex applications like cell replacement. While several studies to date have focused upon the use of hPSC-derived RGCs with genetic variants associated with glaucoma or other optic neuropathies, many of these have largely described cellular phenotypes with only limited advancement into exploring dysfunctional cellular pathways as a consequence of the disease-associated gene variants. Thus, to further advance this field of research, in the current study we leveraged an isogenic hPSC model with a glaucoma-associated mutation in the Optineurin (OPTN) protein, which plays a prominent role in autophagy. We identified an impairment of autophagic-lysosomal degradation and decreased mTORC1 signaling via activation of the stress sensor AMPK, along with subsequent neurodegeneration in OPTN(E50K) RGCs differentiated from hPSCs, and have further validated some of these findings in a mouse model of ocular hypertension. Pharmacological inhibition of mTORC1 in hPSC-derived RGCs recapitulated disease-related neurodegenerative phenotypes in otherwise healthy RGCs, while the mTOR-independent induction of autophagy reduced protein accumulation and restored neurite outgrowth in diseased OPTN(E50K) RGCs. Taken together, these results highlighted that autophagy disruption resulted in increased autophagic demand which was associated with downregulated signaling through mTORC1, contributing to the degeneration of RGCs.

Transforming growth factor-beta and Epithelial-mesenchymal transition is considered an attractive pivotal Genetic-Biomarker for Hepatocellular carcinoma with hepatitis C virus-infection patients

Abstract Introduction/Objective Hepatocellular carcinoma (HCC) is the most common cause of cancer worldwide. HCC is induced by hepatitis C-virus (HCV) which represents a major health problem in Egypt. The transforming growth factor- beta (TGF-β) is a potent cytokine that has a multifunctional pro-fibrotic activity, for enhancing liver-inflammation, fibrosis, tumor-progression, and metastasis. TGF-β has a vital role in the regulation of tumorigenesis, by controlling epithelial-mesenchymal-transition (EMT), apoptosis, proliferation, and differentiation process. The dysregulation of TGF-β, Wnt/β-catenin signaling pathways, by HCV-core protein is implicated in the development of HCC. Methods/Case Report The study aims to determine the effect of the HCV-infection in HCC patients with a set of growth-factors, EMT, and anti-apoptotic protein expression levels by using western blotting and immunohistochemistry staining analysis. Results (if a Case Study enter NA) These results observed an insignificant increase in the expression of TGF-β protein for HCC/HCV-infected cells compared to the HCV-uninfected cells, and the expression of the β-catenin protein level is elevated in the nucleus. Also, it showed that Bcl-2 protein is a significant increase in HCV-infected when compared to HCV-free groups. Positive staining for p53 protein was detected in the HCC/HCV-infected, more than in HCC/HCV-uninfected cells. This data indicated that the core-protein of HCV can switch TGF-β from a tumor suppressor to a tumor promoter by suppressing apoptosis of hepatocytes and increasing EMT expression by activation of Wnt/β-catenin signaling pathway. Therefore, HCV-core protein enhances the nuclear accumulation of β-catenin expression protein to activate downstream target genes, which regulate cell-growth and cell-cycle progression. Conclusion It is speculated that HCV may exert an anti-apoptotic effect, and thus enhance tumorigenesis. Also, the accumulation of nuclear Wnt/β-catenin and p53 correlates with TGF-β expression, typically a late event in hepato- carcinogenesis. Taken together, the expression level of TGF-β, Wnt/β-catenin, Bcl-2, and p53 genotype in HCV is considered an indicator of shortened survival in patients, and may be an attractive clinically pivotal genetic biomarker to mediate liver pathogenesis.

Green Light Drives Embryonic Photosynthesis and Protein Accumulation in Cotyledons of Developing Pea (Pisum sativum L.) Seeds

Photosynthesis is a vital process for seed productivity. It occurs in the leaves and provides developing seeds with the necessary nutrients. Moreover, many crops require photochemical reactions inside the seeds for proper development. The present study aimed to investigate Pisum sativum L. seeds at the middle stage of maturation, which is characterized by the active synthesis of nutrient reserves. Embryonic photosynthesis represents a crucial process to produce cells’ NADP(H) and ATP, which are necessary to convert sucrose into reserve biopolymers. However, it remains unclear how the pea embryo, covered by a coat and pericarp, receives sufficient light to provide energy for photochemical reactions. Recent studies have demonstrated that the photosynthetically active radiation reaching the developing pea embryo has a high proportion of green light. In addition, green light can be utilized in foliar photosynthesis by plants cultivated in shaded conditions. Here, we addressed the role of green light in seed development. Pea plants were cultivated under red and blue (RB) LEDs or red, green, and blue (RGB) LEDs. A Chl a fluorescence transient based on OJIP kinetics was detected at the periphery of the cotyledons isolated from developing seeds. Our findings showed that the addition of green light resulted in an increase in photochemical activity. Furthermore, the mature seeds that developed in the RGB module had a significantly higher weight and more storage proteins. Using a metabolomics approach, we also detected significant differences in the levels of organic acids, carbohydrates, nucleotide monophosphates, and nitrogenous substances between the RB and RGB conditions. Under RGB light, the cotyledons contained more ornithine, tryptophan, arginine, and aspartic acid. These changes indicate an impact of green light on the ornithine–urea cycle and polyamine biosynthesis. These results allow for a deeper understanding of the photochemical processes in embryos of developing seeds grown under a low light intensity. The photosynthetic system in the embryo cell adapts to the shade conditions by using green light.