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Inflammopharmacology Jun 2024The endoplasmic reticulum (ER) is an intracellular organelle that contributes to the folding of proteins and calcium homeostasis. Numerous elements can disrupt its... (Review)
Review
The endoplasmic reticulum (ER) is an intracellular organelle that contributes to the folding of proteins and calcium homeostasis. Numerous elements can disrupt its function, leading to the accumulation of proteins that are unfolded or misfolded in the lumen of the ER, a condition that is known as ER stress. This phenomenon can trigger cell death through the activation of apoptosis and inflammation. Glucoraphanin (GRA) is the predominant glucosinolate found in cruciferous vegetables. Various mechanical and biochemical processes activate the enzyme myrosinase, leading to the hydrolysis of glucoraphanin into the bioactive compound sulforaphane. Sulforaphane is an organosulfur compound that belongs to the isothiocyanate group. It possesses a wide range of activities and has shown remarkable potential as an anti-inflammatory, antioxidant, antitumor, and anti-angiogenic substance. Additionally, sulforaphane is resistant to oxidation, has been demonstrated to have low toxicity, and is considered well-tolerable in individuals. These properties make it a valuable natural dietary supplement for research purposes. Sulforaphane has been demonstrated as a potential candidate drug molecule for managing a range of diseases, primarily because of its potent antioxidant, anti-inflammatory, and anti-apoptotic properties, which can be mediated by modulation of ER stress pathways. This review seeks to cover a wealth of data supporting the broad range of protective functions of sulforaphane, improving various diseases, such as cardiovascular, central nervous system, liver, eye, and reproductive diseases, as well as diabetes, cancer, gastroenteritis, and osteoarthritis, through the amelioration of ER stress in both in vivo and in vitro studies.
PubMed: 38922526
DOI: 10.1007/s10787-024-01506-y -
Planta Jun 2024Knowledge of Ca-ATPases is imperative for improving crop quality/ food security, highly threatened due to global warming. Ca-ATPases modulates calcium, essential for... (Review)
Review
Knowledge of Ca-ATPases is imperative for improving crop quality/ food security, highly threatened due to global warming. Ca-ATPases modulates calcium, essential for stress signaling and modulating growth, development, and immune activities. Calcium is considered a versatile secondary messenger and essential for short- and long-term responses to biotic and abiotic stresses in plants. Coordinated transport activities from both calcium influx and efflux channels are required to generate cellular calcium signals. Various extracellular stimuli cause an induction in cytosolic calcium levels. To cope with such stresses, it is important to maintain intracellular Ca levels. Plants need to evolve efficient efflux mechanisms to maintain Ca ion homeostasis. Plant Ca-ATPases are members of the P-type ATPase superfamily and localized in the plasma membrane and endoplasmic reticulum (ER). They are required for various cellular processes, including plant growth, development, calcium signaling, and even retorts to environmental stress. These ATPases play an essential role in Ca homeostasis and are actively involved in Ca transport. Plant Ca-ATPases are categorized into two major classes: type IIA and type IIB. Although these two classes of ATPases share similarities in protein sequence, they differ in their structure, cellular localization, and sensitivity to inhibitors. Due to the emerging role of Ca-ATPase in abiotic and biotic plant stress, members of this family may help promote agricultural improvement under stress conditions. This review provides a comprehensive overview of P-type Ca-ATPase, and their role in Ca transport, stress signaling, and cellular homeostasis focusing on their classification, evolution, ion specificities, and catalytic mechanisms. It also describes the main aspects of the role of Ca-ATPase in transducing signals during plant biotic and abiotic stress responses and its role in plant development and physiology.
Topics: Stress, Physiological; Calcium-Transporting ATPases; Calcium; Plants; Homeostasis; Calcium Signaling; Signal Transduction; Plant Proteins; Endoplasmic Reticulum
PubMed: 38922354
DOI: 10.1007/s00425-024-04462-7 -
Journal of Functional Biomaterials Jun 2024Nanoparticle (NP)-based solutions for oncotherapy promise an improved efficiency of the anticancer response, as well as higher comfort for the patient. The current... (Review)
Review
Nanoparticle (NP)-based solutions for oncotherapy promise an improved efficiency of the anticancer response, as well as higher comfort for the patient. The current advancements in cancer treatment based on nanotechnology exploit the ability of these systems to pass biological barriers to target the tumor cell, as well as tumor cell organelles. In particular, iron oxide NPs are being clinically employed in oncological management due to this ability. When designing an efficient anti-cancer therapy based on NPs, it is important to know and to modulate the phenomena which take place during the interaction of the NPs with the tumor cells, as well as the normal tissues. In this regard, our review is focused on highlighting different approaches to studying the internalization patterns of iron oxide NPs in simple and complex 2D and 3D in vitro cell models, as well as in living tissues, in order to investigate the functionality of an NP-based treatment.
PubMed: 38921542
DOI: 10.3390/jfb15060169 -
Journal of Fungi (Basel, Switzerland) Jun 2024The sustainable production of natural compounds is increasingly important in today's industrial landscape. This study investigates the metabolic engineering of for the...
The sustainable production of natural compounds is increasingly important in today's industrial landscape. This study investigates the metabolic engineering of for the efficient biosynthesis of valuable carotenoids: canthaxanthin, zeaxanthin, and astaxanthin. Utilizing a tailored parental yeast strain, Sp_Bc, we optimized the carotenoid pathway by screening and identifying CrtW and CrtZ enzymatic variants. The CrtW variant from sp. achieved a canthaxanthin titer of 425.1 ± 69.1 µg/L, while the CrtZ variant from achieved a zeaxanthin titer of 70.5 ± 10.8 µg/L. Additionally, we optimized carotenoid production by exploring enzyme fusion strategies for all three studied carotenoids and organelle compartmentalization specifically for enhancing astaxanthin synthesis. We further improved carotenoid production by integrating the optimal gene constructs into the yeast genome and deleting the gene, enabling the use of sucrose as a carbon source. The engineered strain Sp_Bc-Can001 was evaluated in a 5 L bioreactor fermentation, achieving a notable canthaxanthin titer of 60.36 ± 1.51 mg/L using sucrose. This research conclusively establishes as a viable platform for efficient carotenoid biosynthesis and, for the first time in this yeast system, illustrates sucrose's viability as a carbon source for canthaxanthin production. These findings pave the way for sustainable, cost-effective carotenoid production at an industrial scale.
PubMed: 38921419
DOI: 10.3390/jof10060433 -
Journal of Fungi (Basel, Switzerland) May 2024Mitochondria, as the core metabolic organelles, play a crucial role in aerobic respiration/biosynthesis in fungi. Numerous studies have demonstrated a close relationship...
Mitochondria, as the core metabolic organelles, play a crucial role in aerobic respiration/biosynthesis in fungi. Numerous studies have demonstrated a close relationship between mitochondria and virulence and drug resistance. Here, we report an octapeptide-aminopeptidase located in the mitochondrial matrix named Oct1p. Its homolog in the model fungus is one of the key proteins in maintaining mitochondrial respiration and protein stability. In this study, we utilized evolutionary tree analysis, gene knockout experiments, mitochondrial function detection, and other methods to demonstrate the impact of Oct1p on the mitochondrial function of . Furthermore, through transcriptome analysis, real-time quantitative PCR, and morphological observation, we discovered that the absence of Oct1p results in functional abnormalities in , affecting hyphal growth, cell adhesion, and biofilm formation. Finally, the in vivo results of the infection of larvae and vulvovaginal candidiasis in mice indicate that the loss of Oct1p led to the decreased virulence of . In conclusion, this study provides a solid theoretical foundation for treating Candida diseases, developing new targeted drugs, and serves as a valuable reference for investigating the connection between mitochondria and virulence in other pathogenic fungi.
PubMed: 38921377
DOI: 10.3390/jof10060391 -
Current Issues in Molecular Biology May 2024Skin aging is an unavoidable natural phenomenon caused by intrinsic and extrinsic factors. In modern society, the pursuit of a wrinkle-free and aesthetically appealing...
Skin aging is an unavoidable natural phenomenon caused by intrinsic and extrinsic factors. In modern society, the pursuit of a wrinkle-free and aesthetically appealing face has gained considerable prominence. Numerous studies have aimed at mitigating the appearance of facial wrinkles. Antiaging research focused on regulating the function of mitochondria, the main reactive oxygen species-generating organelles, has been extensively conducted. In this study, we investigated the correlation between facial wrinkles and the expression of , considering the association of this gene with mitochondrial function, to identify its potential as a target for exploring antiaging cosmetic materials. We elucidated the role of in the skin and identified five bioactive materials that modulated its expression. The effectiveness of these materials was verified through in vitro experiments on human dermal fibroblasts. We prepared cosmetic formulations incorporating the five materials and confirmed their ability to enhance dermal collagen in three-dimensional skin models and reduce facial wrinkles under the eyes and nasolabial fold areas in human subjects. The study findings have significant implications for developing novel antiaging cosmetic formulations by reinforcing mitochondrial functions.
PubMed: 38920974
DOI: 10.3390/cimb46060302 -
Audiology Research Jun 2024Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires...
A New Perspective to Interpret How the Vestibular Efferent System Correlates the Complexity of Routine Balance Maintenance with Management of Emergency Fall Prevention Strategies.
Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and it can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information simultaneously transmitted to the maculae with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system causes macular otolithic membrane movement through the STO, which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.
PubMed: 38920965
DOI: 10.3390/audiolres14030044 -
Cells Jun 2024Venetoclax and obinutuzumab are becoming frontline therapies for chronic lymphocytic leukemia (CLL) patients. Unfortunately, drug resistance still occurs, and the...
Lysosome-Disrupting Agents in Combination with Venetoclax Increase Apoptotic Response in Primary Chronic Lymphocytic Leukemia (CLL) Cells Mediated by Lysosomal Cathepsin D Release and Inhibition of Autophagy.
Venetoclax and obinutuzumab are becoming frontline therapies for chronic lymphocytic leukemia (CLL) patients. Unfortunately, drug resistance still occurs, and the combination could be immunosuppressive. Lysosomes have previously been identified as a target for obinutuzumab cytotoxicity in CLL cells, but the mechanism remains unclear. In addition, studies have shown that lysosomotropic agents can cause synergistic cell death in vitro when combined with the BTK inhibitor, ibrutinib, in primary CLL cells. This indicates that targeting lysosomes could be a treatment strategy for CLL. In this study, we have shown that obinutuzumab induces lysosome membrane permeabilization (LMP) and cathepsin D release in CLL cells. Inhibition of cathepsins reduced obinutuzumab-induced cell death in CLL cells. We further determined that the lysosomotropic agent siramesine in combination with venetoclax increased cell death in primary CLL cells through an increase in reactive oxygen species (ROS) and cathepsin release. Siramesine treatment also induced synergistic cytotoxicity when combined with venetoclax. Microenvironmental factors IL4 and CD40L or incubation with HS-5 stromal cells failed to significantly protect CLL cells from siramesine- and venetoclax-induced apoptosis. We also found that siramesine treatment inhibited autophagy through reduced autolysosomes. Finally, the autophagy inhibitor chloroquine failed to further increase siramesine-induced cell death. Taken together, lysosome-targeting drugs could be an effective strategy in combination with venetoclax to overcome drug resistance in CLL.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Lysosomes; Apoptosis; Autophagy; Cathepsin D; Reactive Oxygen Species; Drug Synergism; Cell Line, Tumor
PubMed: 38920669
DOI: 10.3390/cells13121041 -
Cells Jun 2024Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma...
Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma patients and controls and compared their characteristics with other biomarkers such as cytokines. Glaucoma patients exhibited higher exosome particle counts and smaller sizes compared to controls. Higher exosome density was correlated with more severe visual field loss. Conversely, concentrations of aqueous humor cytokines, particularly PD-L1, were primarily associated with intraocular pressure, and none of the cytokines showed a significant association with visual field damage. This may reflect the characteristics of exosomes, which are advantageous for crossing various biological barriers. Exosomes may contain more information about glaucoma functional damage occurring in the retina or optic nerve head. This highlights the potential importance of exosomes as signaling mediators distinct from other existing molecules.
Topics: Humans; Aqueous Humor; Exosomes; Biomarkers; Glaucoma; Cytokines; Female; Male; Middle Aged; Aged; Intraocular Pressure; Case-Control Studies
PubMed: 38920659
DOI: 10.3390/cells13121030 -
Cells Jun 2024Neurodegenerative disorders are affecting millions of people worldwide, impacting the healthcare system of our society. Among them, Alzheimer's disease (AD) is the most...
Neurodegenerative disorders are affecting millions of people worldwide, impacting the healthcare system of our society. Among them, Alzheimer's disease (AD) is the most common form of dementia, characterized by severe cognitive impairments. Neuropathological hallmarks of AD are β-amyloid (Aβ) plaques and neurofibrillary tangles, as well as endoplasmic reticulum and mitochondria dysfunctions, which finally lead to apoptosis and neuronal loss. Since, to date, there is no definitive cure, new therapeutic and prevention strategies are of crucial importance. In this scenario, cannabinoids are deeply investigated as promising neuroprotective compounds for AD. In this study, we evaluated the potential neuroprotective role of cannabinerol (CBNR) in an in vitro cellular model of AD via next-generation sequencing. We observed that CBNR pretreatment counteracts the Aβ-induced loss of cell viability of differentiated SH-SY5Y cells. Moreover, a network-based transcriptomic analysis revealed that CBNR restores normal mitochondrial and endoplasmic reticulum functions in the AD model. Specifically, the most important genes regulated by CBNR are related mainly to oxidative phosphorylation (, , , ), protein folding () and degradation (, , ), and glucose () and lipid (, , ) metabolism. Therefore, these results suggest that CBNR could be a new neuroprotective agent helpful in the prevention of AD dysfunctions.
Topics: Humans; Alzheimer Disease; Mitochondria; Endoplasmic Reticulum; Cannabinoids; Amyloid beta-Peptides; Endoplasmic Reticulum Chaperone BiP; Cell Line, Tumor; Gene Expression Profiling; Transcriptome; Cell Survival; Neuroprotective Agents; Models, Biological; Gene Regulatory Networks
PubMed: 38920643
DOI: 10.3390/cells13121012