Stress-related Proteins Research Articles

Association of serum and local GRP78 and CHOP expressions with disease progression in patients with non-traumatic osteonecrosis of femoral head

BackgroundThe endoplasmic reticulum stress (ER stress) has been involved in various musculoskeletal disorders including non-traumatic osteonecrosis of femoral head (NT-ONFH).ObjectiveThe current study aimed to investigate the association of glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) expressions in serum and femoral head (FH) tissues with NT-ONFH’s severity.MethodsWe enrolled NT-ONFH patients (n = 150) alongside healthy controls (HCs, n = 150). Meanwhile, 49 patients with femoral neck fracture (FNF) were also enrolled. Serum CHOP and GRP78 levels were determined through enzyme linked immunosorbent assay (ELISA). Local CHOP and GRP78 expressions were detected by immunohistochemistry, western blot, alongside real-time polymerase chain reaction (RT-PCR). Radiographic severity was assessed by FICAT grading system. The visual analogue scale (VAS) together with Harris hip score (HHS) were utilized to determine symptomatic severity.ResultsSerum CHOP and GRP78 levels were markedly increased in NT-ONFH patients than HCs. NT-ONFH patients at FICAT stage 4 showed significant higher serum CHOP and GRP78 levels in contrast with those at stage 3. Furthermore, patients at stage 3 demonstrated higher serum CHOP and GRP78 levels than those at stage 2. There was a positive correlation observed between the serum CHOP and GRP78 levels and the severity of the FICAT stages. A total of 42 ONFH patients at FICAT stage 3, 40 patients at FICAT stage 4, and 49 FNF patients received total hip replacement (THR). The mRNA and protein levels of CHOP and GRP78 were elevated in necrotic area compared to the non-necrotic area of ONFH patients and the FH tissues of FNF patients with statistical significance. The expression levels of CHOP and GRP78 within the local tissues were significantly elevated in patients at FICAT stage 4 as opposed to those at stage 3. Besides, ROC curve analysis indicated that serum and local CHOP and GRP78 expressions may act as indicators of disease progression. The levels of CHOP and GRP78, both in serum and at the local site, were in a positive correlation with VAS scores but an inverse relationship with HHS.ConclusionsSerum and local GRP78 as well as CHOP expressions were positively linked with disease progression in NT-ONFH patients. Potential therapeutics targeting ER stress related protein may serve as a method for alleviating NT-ONFH.

The mechanism of endoplasmic reticulum (ER) stress in cell apoptosis and ROS (reactive oxygen species) of CNE2 cell line induced by single wall carbon nanohorn (SWCNH)

IntroductionThe interaction between the materials themselves and cancer cells are rarely explored. Therefore, the biological roles of raw single wall carbon nanohorn (SWCNH) on endoplasmic reticulum (ER) stress in the apoptosis of CNE2 were explored.MethodsTherefore, ERS of CNE2 cells was induced by SWCNH, and 4-phenylbutyrate (4-PBA) was selected as a inhibitor of ERS. CNE2 cells were co-cultured with SWCNH, 4-PBA and SWCNH+4-PBA, respectively. Furthermore, the apoptotic status of CNE2 cells and its ROS (Reactive oxygen species) levels were determined. Moreover, the apoptotic protein expression of caspase 3 (cysteinyl aspartate specific proteinase 3), the expression levels of ER pathway protein eIF2α, ATF4 and CHOP, or the OS (Oxidative stress)-related proteins NQO1, GCLC, HO-1, and Nrf2 was detected, respectively.ResultsCNE2 apoptotic rate, ROS levels, the caspase 3 or ER pathway proteins ATF4 and CHOP expression, even the NQO1, GCLC, HO-1, and Nrf2 levels of oxidative stress-related proteins in the groups of SWCNH and SWCNH+4-PBA were higher compared to the control group. Moreover, these indicators were higher compared to the group of SWCNH+4-PBA (p < 0.05).DiscussionER stress is the key possible mechanism of CNE2 apoptosis induced by SWCNH. After injury of ERS, SWCNH causes oxidative stress injury, which may eventually lead to apoptosis of CNE2 cells.

Mechanisms of drought tolerance in Moringa: Strategies for mitigation and adaptation – Review

Moringa oleifera, often called the "miracle tree," is renowned for its resilience to harsh environmental conditions, particularly drought. This review explores the mechanisms by which Moringa tolerates drought stress, making it a vital crop in arid and semi-arid regions. Morphological, physiological, biochemical, and molecular adaptations attribute the tree's drought tolerance. Key mechanisms include an extensive root system that enhances water uptake, efficient water use through stomatal regulation, and the accumulation of Osmo protectants such as proline. Additionally, Moringa activates antioxidant enzymes that mitigate oxidative stress under drought conditions, safeguarding cellular integrity. Molecular responses play a significant role as well, with the upregulation of drought-responsive genes and stress-related proteins that enhance the tree’s ability to cope with water scarcity. These adaptive traits not only contribute to Moringa's survival but also improve its productivity under water-limited conditions. Beyond its environmental resilience, Moringa holds significant socioeconomic value. Its rich nutritional content, medicinal properties, and potential for income generation make it a critical crop for addressing food security and poverty, especially in developing regions. This review highlights the importance of promoting Moringa cultivation as a sustainable agricultural practice in drought-prone areas. In conclusion, understanding and leveraging Moringa's drought tolerance mechanisms can contribute to climate change mitigation and adaptation strategies. Expanding its cultivation could lead to more resilient agricultural systems, providing both environmental and socioeconomic benefits. Continued research is essential to optimize its use and ensure its widespread adoption in vulnerable regions.

A Dive Into Yeast's Sugar Diet-Comparing the Metabolic Response of Glucose, Fructose, Sucrose, and Maltose Under Dynamic Feast/Famine Conditions.

Microbes experience dynamic conditions in natural habitats as well as in engineered environments, such as large-scale bioreactors, which exhibit increased mixing times and inhomogeneities. While single perturbations have been studied for several organisms and substrates, the impact of recurring short-term perturbations remains largely unknown. In this study, we investigated the response of Saccharomyces cerevisiae to repetitive gradients of four different sugars: glucose, fructose, sucrose, and maltose. Due to different transport mechanisms and metabolic routes, nonglucose sugars lead to varied intracellular responses. To characterize the impact of the carbon sources and the dynamic substrate gradients, we applied both steady-state and dynamic cultivation conditions, comparing the physiology, intracellular metabolome, and proteome. For maltose, the repeated concentration gradients led to a significant decrease in biomass yield. Under glucose, fructose, and sucrose conditions, S. cerevisiae maintained the biomass yield observed under steady-state conditions. Although the physiology was very similar across the different sugars, the intracellular metabolome and proteome were clearly differentiated. Notably, the concentration of upper glycolytic enzymes decreased for glucose and maltose (up to -60% and -40%, respectively), while an increase was observed for sucrose and fructose when exposed to gradients. Nevertheless, for all sugar gradient conditions, a stable energy charge was maintained, ranging between 0.78 and 0.89. This response to maltose is particularly distinct compared to previous single-substrate pulse experiments or limitation to excess shifts, which led to maltose-accelerated death in earlier studies. At the same time, enzymes of lower glycolysis were elevated. Interestingly, common stress-related proteins (GO term: cellular response to oxidative stress) decreased during dynamic conditions.

Unlocking the therapeutic potential of canagliflozin in NAFLD: Insights into AMPK/SIRT1-mediated lipophagy.

This study aimed to explore the possible anti-NAFLD effects of CANA in rats and HepG2 cells, focusing on AMPK/SIRT1-mediated lipophagy. Wistar rats were assigned to four groups: control group, NAFLD group, NAFLD+CANA group, and NAFLD+CANA+chloroquine (CQ) group, where CQ served as autophagy inhibitor. HepG2 cells were also divided into four groups: control group, NAFLD group, NAFLD+CANA group, and NAFLD+CANA+compound C (Comp C) group, where Comp C served as AMPK inhibitor. The histopathological examination showed that CANA alleviated hepatic and intracellular lipid deposition in rats and HepG2 cells. CANA induced lipophagy by increasing LC3-II levels and lowering both p62 and perilipin 2 levels in rats and HepG2 cells, in addition to decreasing mTOR protein expression in rats' livers. These outcomes were associated with upregulation of the lipophagy regulator Rab7 and downregulation of the ER stress-related protein CHOP. CANA enhanced autophagic engulfment of lipid droplets while decreased ER stress and mitochondrial damage in rats' livers, as demonstrated by TEM. In rats, CANA improved hyperglycemia, hyperinsulinemia, dyslipidemia, and obesity. In HepG2 cells, CANA's effects were linked to increased phosphorylated AMPK level and enhanced SIRT1 level and expression. However, blocking lipophagy in rats and AMPK in HepG2 cells markedly weakened CANA's protective effects against NAFLD. CANA ameliorated NAFLD via enhancing AMPK/SIRT1-mediated lipophagy, suggesting its potential as a therapeutic intervention for this metabolic disorder.

Bioprocess exploitation of microaerobic auto-induction using the example of rhamnolipid biosynthesis in Pseudomonas putida KT2440

BackgroundIn biomanufacturing of surface-active agents, such as rhamnolipids, excessive foaming is a significant obstacle for the development of high-performing bioprocesses. The exploitation of the inherent tolerance of Pseudomonas putida KT2440, an obligate aerobic bacterium, to microaerobic conditions has received little attention so far. Here low-oxygen inducible promoters were characterized in biosensor strains and exploited for process control under reduction of foam formation by low aeration and stirring rates during biosynthesis of rhamnolipids.ResultsIn this study, homologous promoters of P. putida inducible under oxygen limitation were identified by non-targeted proteomic analyses and characterized by fluorometric methods. Proteomics indicated a remodeling of the respiratory chain and the regulation of stress-related proteins under oxygen limitation. Of the three promoters tested in fluorescent biosensor assays, the promoter of the oxygen-sensitive cbb3-type cytochrome c oxidase gene showed high oxygen-dependent controllability. It was used to control the gene expression of a heterologous di-rhamnolipid synthesis operon in an auto-inducing microaerobic two-phase bioprocess. By limiting the oxygen supply via low aeration and stirring rates, the bioprocess was clearly divided into a growth and a production phase, and sources of foam formation were reduced. Accordingly, rhamnolipid synthesis did not have to be controlled externally, as the oxygen-sensitive promoter was autonomously activated as soon as the oxygen level reached microaerobic conditions. A critical threshold of about 20% oxygen saturation was determined.ConclusionsUtilizing the inherent tolerance of P. putida to microaerobic conditions in combination with the application of homologous, low-oxygen inducible promoters is a novel and efficient strategy to control bioprocesses. Fermentation under microaerobic conditions enabled the induction of rhamnolipid production by low oxygen levels, while foam formation was limited by low aeration and stirring rates.

Alterations in Autophagic Function and Endoplasmic Reticulum Stress Markers in the Peripheral Blood Mononuclear Cells of Patients on Hemodialysis.

Oxidative stress, endoplasmic reticulum (ER) stress, and alterations in autophagy activity have been described as prominent factors mediating many pathological processes in chronic kidney disease (CKD). The accumulation of misfolded proteins in the ER may stimulate the unfolded protein response (UPR). The interplay between autophagy and UPR in hemodialysis (HD) patients remains unclear. The aim of the present study was to explore the associations between serum oxidative stress markers, autophagy activity, and ER stress markers in the peripheral blood mononuclear cells (PBMCs) of patients on HD. Autophagy and ER stress-related protein expression levels in PBMCs were measured using western blotting. The redox state of human serum albumin was measured via high-performance liquid chromatography. Levels of the microtubule associated protein light chain 3 (LC3)-II, BECLIN1, and p62/SQSTM1 proteins were significantly increased in PBMCs of HD patients compared to healthy subjects. The PBMCs in HD patients also displayed augmented glucose-regulated protein 78 kDa (GRP78), phosphorylated eukaryotic translation initiation factor 2, subunit 1 alpha (p-eIF2α), and activating transcription factor 6 (ATF6) levels (p < 0.05). Additionally, nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) levels were elevated in the PBMCs of HD patients, compared to those of healthy subjects. Correlation analysis showed that the redox status of albumin was significantly correlated with the p62 protein level in PBMCs. Compared to healthy controls, we found elevated autophagosome formation in HD patients. Increased expression of ER stress markers was also observed in HD patients. Furthermore, increased p62 expression was positively correlated with the protein expression of NRF2, as well as a reduced form of serum albumin (human mercaptalbumin; HMA), in HD patients.

The role of the NOTCH1 signaling pathway in the maintenance of mesenchymal stem cell stemness and chondrocyte differentiation and its potential in the treatment of osteoarthritis

ObjectiveThis study aims to explore the potential role of mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA), particularly the function of the NOTCH1 signaling pathway in maintaining the stemness of MSCs and in chondrocyte differentiation.MethodsUtilizing diverse analytical techniques on an osteoarthritis dataset, we unveil distinct gene expression patterns and regulatory relationships, shedding light on potential mechanisms underlying the disease. Techniques used include the culture of MSCs, induction of differentiation into chondrocytes, establishment of stable cell lines, Western Blot, and immunofluorescence. Through the construction of lentiviruses overexpressing and knocking out NOTCH1, the effects of NOTCH1 on the stemness of MSCs and chondrocyte differentiation were investigated. Additionally, the effects of NOTCH1 on chondrocyte homeostasis and apoptosis were evaluated by adding the EZH2 inhibitor GSK126 and the endoplasmic reticulum stress inducer tunicamycin.ResultsExperimental results demonstrated that NOTCH1 expression can influence the maintenance of MSC stemness and chondrocyte differentiation by regulating EZH2. Knockout of NOTCH1 decreased the expression of chondrocyte markers, while overexpression increased their expression. Under conditions of endoplasmic reticulum stress, NOTCH1 expression helped reduce the expression of stress-related proteins, maintain chondrocyte homeostasis, and inhibit apoptosis.ConclusionThe NOTCH1 signaling pathway plays a crucial role in maintaining the stemness of MSCs, differentiating into chondrocytes, and in the treatment of osteoarthritis. NOTCH1 influences the differentiation fate of MSCs and the homeostasis of chondrocytes by regulating EZH2 and other related genes, offering new targets and strategies for the treatment of diseases like osteoarthritis.

Photoacclimation strategies of Chlamydomonas reinhardtii in response to high-light stress in stationary phase.

Under ideal conditions, Chlamydomonas reinhardtii can photoacclimate to excess light through various short- and long-term mechanisms. However, how microalgae handle excess light stress once they exit exponential growth, and especially in stationary phase, is less understood. Our study explored C. reinhardtii's photoprotection capacity and acclimation strategies during high-light stress once batch culture growth reached stationary phase. We monitored cultures of wildtype strain (CC125) over five days once they reached stationary phase under both low-light (LL) and high-light (HL) conditions. Under HL, many photosynthetic proteins were degraded but the stress-related light harvesting complex protein (LHCSR) was rapidly induced and contributed to the rapid activation of nonphotochemical quenching (NPQ). However, the LHCSR3-defective mutant (CC4614, npq4) lacked the rapid induction of quenching typical of post-exponential cultures, indicating that LHCSR3 is required for this response in stationary phase. Collectively, the main strategy for photoacclimation in stationary phase appears to be a dramatic reduction of photosystems while maintaining LHCII-LHCSR antenna complexes that prime the antenna for rapid activation of quenching upon light exposure. Part of this response to HL involves a resumption of cell growth after two days, that we hypothesized is due to the stimulation of growth-regulating pathways due to increased metabolite pools from the HL-induced protein turnover in the cell, something that remains to be tested. These findings demonstrate how C. reinhardtii manages high-light stress during stationary phases to maximize longevity.

Best1 mitigates ER stress induced by the increased cellular microenvironment stiffness in epilepsy.

Changes in brain tissue stiffness are closely linked to the development and diseases of the nervous system. Endoplasmic reticulum (ER) stress plays a role in various pathological processes related to epilepsy. However, the relationship between stiffness changes, ER stress, and epilepsy remains unclear. This study aimed to investigate the impact of Best1 upregulation on alleviating ER stress and the underlying mechanism. Additionally, we proposed a protective strategy to prevent cell death resulting from ER stress in epilepsy. This study investigated the expression levels of ER stress-related proteins in epileptic tissues of varying stiffness. Atomic force microscopy revealed differences in stiffness across various lesion regions in patients with epilepsy. The expression levels of ECM and ER stress-related proteins were elevated in tissues with higher stiffness. Polypropionamide hydrogels were used to simulate extracellular matrix (ECM) with varying stiffness levels. Basal ER stress increased in the stiffer hydrogel substrates. Furthermore, the calcium-activated anion channel Bestrophin 1 (Best1) mitigated ER stress induced by both the stiffer substrate and thapsigargin. The loss-of-function mutations in Best1 inhibited this activity. The underlying mechanism involves the upregulation of the endosomal sorting complex required for the transport (ESCRT) components by Best1, which helps mitigate ER stress. These findings suggest that increased stiffness of the cellular microenvironment may contribute to neuronal death during epileptogenesis. Additionally, Best1 upregulation may serve as a protective strategy against excessive ER stress-induced neuronal damage in epilepsy.

Differences in gene expression between high and low tolerance rainbow trout (Oncorhynchus mykiss) to acute thermal stress.

Understanding the mechanisms that underlie the adaptive response of ectotherms to rising temperatures is key to mitigate the effects of climate change. We assessed the molecular and physiological processes that differentiate between rainbow trout (Oncorhynchus mykiss) with high and low tolerance to acute thermal stress. To achieve our goal, we used a critical thermal maximum trial in two strains of rainbow trout to elicit loss of equilibrium responses to identify high and low tolerance fish. We then compared the hepatic transcriptome profiles of high and low tolerance fish relative to untreated controls common to both strains to uncover patterns of differential gene expression and to gain a broad perspective on the interacting gene pathways and functional processes involved. We observed some of the classic responses to increased temperature (e.g., induction of heat shock proteins) but these responses were not the defining factors that differentiated high and low tolerance fish. Instead, high tolerance fish appeared to suppress growth-related functions, enhance certain autophagy components, better regulate neurodegenerative processes, and enhance stress-related protein synthesis, specifically spliceosomal complex activities, mRNA regulation, and protein processing through post-translational processes, relative to low tolerance fish. In contrast, low tolerance fish had higher transcript diversity and demonstrated elevated developmental, cytoskeletal, and morphogenic, as well as lipid and carbohydrate metabolic processes, relative to high tolerance fish. Our results suggest that high tolerance fish engaged in processes that supported the prevention of further damage by enhancing repair pathways, whereas low tolerance fish were more focused on replacing damaged cells and their structures.

Antioxidant Bio-Compounds from Chestnut Waste: A Value-Adding and Food Sustainability Strategy.

In an era of escalating environmental challenges, converting organic residues into high-value bioactive compounds provides a sustainable way to reduce waste and enhance resource efficiency. This study explores the potential of the circular bioeconomy through the valorization of agricultural byproducts, with a focus on the antioxidant properties of specific chestnut burr cultivars. Currently, over one-third of food production is wasted, contributing to both humanitarian and environmental crises. Through circular bioeconomy, we can transform biological waste into valuable products for use in fields like food innovation and sustainability. The antioxidant effects of three chestnut cultivars, Bastarda Rossa, Cecio, and Marroni, were assessed through in vitro assays, highlighting their potential to combat oxidative stress-an important factor for health-related applications. The characterization of the three cultivars showed the major presence of ellagic acid and gallic acid in the extract, renowned for their antioxidant activity. In vitro assays evaluated the phenolic and flavonoid content, as well as the antioxidant activity of the three extracts, confirming the cultivar Cecio as the richest in these bioactive compounds and the most performative in antioxidant assays. In vitro antioxidant and oxidative stress recovery assays on SaOS-2, fibroblast, and chondrocyte cell lines displayed a strong antioxidant activity. Furthermore, the cytotoxicity assay demonstrated the safety of all three extracts in the tested human cell lines. In silico docking simulations further validated the biological relevance of these compounds by predicting strong hydrophobic and polar interactions with oxidative stress-related protein targets. Overall, this study demonstrates the antioxidant properties of chestnut byproducts. The findings contribute to the development of functional foods, nutraceuticals, and other applications, underscoring the role of chestnut cultivars in advancing circular bioeconomy practices.

Adapting cucurbits to diverse environments: Insights from GEI studies

Recently, there has been increasing concern about crop failures and yield gaps attributed to climate change, as certain genotypes fail to achieve the desired yields or quality due to variations in external temperatures. To address this issue, breeders are working to develop climate-resilient varieties by incorporating relevant genes into cultivars or genotypes or by utilizing desirable source plants in the breeding process. Additionally, management practices are being implemented to mitigate environmental impacts. Multi-environmental trials (METs) are commonly employed by breeders to assess the adaptability of specific genotypes or cultivars across different locations and time periods. The data collected from these trials is then analyzed using stability statistical models designed for stability analysis, which allows for the evaluation of cultivar or genotype performance under varied environmental conditions. Over the past six decades, there has been a significant focus on modeling genotype-environment interactions (GEI), leading to the development of various mathematical methods and models to decipher GEI in METs, often referred to as "stability analyses." In the era of omics, phenomics techniques have emerged as valuable tools for screening morphological and physiological variations in genotypes resulting from environmental factors. This review emphasizes the importance of GEI in cucurbits, highlighting how environmental stress can alter physiological traits such as stomatal conductance, single leaf area, rooting depth, and membrane composition. Furthermore, it notes the accumulation of stress-related proteins under stress conditions, underscoring the significance of understanding GEI for effective crop management and breeding programs.

MiR-378 exaggerates angiogenesis and bone erosion in collagen-induced arthritis mice by regulating endoplasmic reticulum stress

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by pain, inflammation, and discomfort in the synovial joints. It is critical to understand the pathological mechanisms of RA progression. MicroRNA-378 (miR-378) is highly expressed in the synovium of RA patients and positively correlated with disease severity, but its function and underlying mechanisms remain poorly understood. In this study, miR-378 transgenic (miR-378high) mice were used to construct the collagen-induced arthritis (CIA) model for exploring the role of miR-378 in RA development. miR-378high CIA mice showed accelerated RA development, as evidenced by exaggerated joint swelling and bone structural deformities. More severe endoplasmic reticulum (ER) stress and the consequent angiogenesis and osteoclastogenesis were also activated in the synovial tissue and calcaneus, respectively, in the miR-378high group, suggesting that ER plays a significant role in miR-378-mediated RA pathogenesis. Upon in vitro RA induction, fibroblast-like synoviocytes (FLSs) isolated from miR-378high mice showed a higher expression level of ER stress markers. The conditioned medium (CM) from RA-FLSs of miR-378high mice stimulated more intensive angiogenesis and osteoclastogenesis. The ER stress-related protein Crebrf was identified as a downstream target of miR-378. Crebrf knockdown diminished the promoting effect of miR-378 on ER stress, as well as its downstream angiogenesis and osteoclastogenesis activities. Tail vein injection of anti-miR-378 lentivirus in an established RA mouse model was shown to ameliorate RA progression. In conclusion, miR-378 amplified RA development by promoting ER stress and downstream angiogenesis and osteoclastogenesis, thus indicating that miR-378 may be a potential therapeutic target for RA treatment.

Potent phytoceuticals cocktail exhibits anti-inflammatory and antioxidant activity on LPS-triggered RAW264.7 macrophages in vitro.

Chronic inflammatory conditions, which include respiratory diseases and other ailments, are characterized by persistent inflammation and oxidative stress, and represent a significant health burden, often inadequately managed by current therapies which include conventional inhaled bronchodilators and oral or inhaled corticosteroids in the case of respiratory disorders. The present study explores the potential of Vedicinals®9 Advanced, a polyherbal formulation, to mitigate LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages. The cells were pre-treated with Vedicinals®9 Advanced, followed by exposure to LPS to induce an inflammatory response. Key experimental outcomes were assessed, including nitric oxide (NO) and reactive oxygen species (ROS) production, as well as the expression of inflammatory and oxidative stress-related genes and proteins. Vedicinals®9 Advanced significantly reduced LPS-induced NO and ROS production, indicating strong anti-inflammatory and antioxidant properties. Additionally, the formulation downregulated the LPS-upregulated mRNA expression of pro-inflammatory cytokines, such as TNF-α and CXCL1, and oxidative stress markers, including GSTP1 and NQO1. Furthermore, Vedicinals®9 Advanced downregulated the LPS-induced protein expression of the chemokines CCL2 and CCL6, the LPS co-receptor, CD14, and the pro-inflammatory cytokines G-CSF and IL-1β. These findings highlight the potential of Vedicinals®9 Advanced as a therapeutic option for managing CRDs and other inflammatory conditions. The formulation's ability to simultaneously target inflammation and oxidative stress suggests it may offer advantages over existing treatments, with potential for broader application in inflammatory diseases.

Stress on the Endoplasmic Reticulum Impairs the Photosynthetic Efficiency of Chlamydomonas.

Stress on the Endoplasmic reticulum (ER) can severely disrupt cellular function by impairing protein folding and post-translational modifications, thereby leading to the accumulation of poor-quality proteins. However, research on its impact on photosynthesis remains limited. In this study, we investigated the impact of ER stress on the photosynthetic efficiency of Chlamydomonas reinhardtii using pharmacological inducers, tunicamycin (TM) and brefeldin A (BFA), which specifically target the ER. Our measurements of photosynthetic parameters showed that these ER stress-inducing compounds caused a significant decline in photosynthetic efficiency. A proteomic analysis confirmed that TM and BFA effectively induce ER stress, as evidenced by the upregulation of ER stress-related proteins. Furthermore, we observed a widespread downregulation of photosynthesis-related proteins, which is consistent with the results obtained from our measurements of photosynthetic parameters. These findings suggest that the stress on ER has a profound impact on chloroplast function, disrupting photosynthetic processes. This study highlights the critical interdependence between the ER and chloroplasts, and it underscores the broader implications of ER stress on the cellular metabolism and energy efficiency of photosynthetic organisms.

Entacapone alleviates muscle atrophy by modulating oxidative stress, proteolysis, and lipid aggregation in multiple mice models

BackgroundSkeletal muscle atrophy significantly affects quality of life and has socio-economic and health implications. This study evaluates the effects of entacapone (ENT) on skeletal muscle atrophy linked with oxidative stress and proteolysis.MethodsC2C12 cells were treated with dexamethasone (Dex) to simulate muscle atrophy. Four murine models were employed: diaphragm atrophy from mechanical ventilation, Dex-induced atrophy, lipopolysaccharide (LPS)-induced atrophy, and hyperlipidemia-induced atrophy. Each model utilized entacapone (10 mg/kg), with sample sizes: Control (9), MV (11), MV + ENT (5) for diaphragm atrophy; Control (4), Dex (4), Dex + ENT (5) for Dex model; Control (4), LPS (4), LPS + ENT (5) for LPS model; and similar for hyperlipidemia. Measurements included muscle strength, myofiber cross-sectional area (CSA), proteolysis, oxidative stress markers [uperoxide dismutase 1 (SOD1), uperoxide dismutase 2 (SOD2), 4-hydroxynonenal (4-HNE)], and lipid levels.ResultsOur findings confirm Dex-induced muscle atrophy, evidenced by increased expression of muscle atrophy-associated proteins, including Atrogin-1 and Murf-1, along with decreased diameter of C2C12 myotubes. Atrogin-1 levels rose by 660.6% (p &amp;lt; 0.05) in the Dex group compared to control, while entacapone reduced Atrogin-1 by 84.4% (p &amp;lt; 0.05). Similarly, Murf-1 levels increased by 365% (p &amp;lt; 0.05) in the Dex group and were decreased by 89.5% (p &amp;lt; 0.05) with entacapone. Dexamethasone exposure induces oxidative stress, evidenced by the upregulation of oxidative stress-related proteins Sod1, Sod2, and 4-HNE. Entacapone significantly reduced the levels of these oxidative stress markers, enhancing GSH-PX content by 385.6% (p &amp;lt; 0.05) compared to the Dex-treated group. Additionally, ENT effectively reduced the Dex-induced increase in MDA content by 63.98% (p &amp;lt; 0.05). Furthermore, entacapone effectively prevents the decline in diaphragm muscle strength and myofiber CSA in mice. It also mitigates diaphragm oxidative stress and protein hydrolysis. Additionally, entacapone exhibits the ability to attenuate lipid accumulation in the gastrocnemius muscle of hyperlipidemic mice and alleviate the reduction in muscle fiber CSA.ConclusionOur findings suggest that entacapone is a promising therapeutic candidate for muscle atrophy, functioning through the reduction of oxidative stress, proteolysis, and lipid aggregation. Future research should explore the underlying mechanisms and potential clinical applications of entacapone in muscle-wasting conditions.

Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury.

Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study aimed to assess senescence and stress-related pathways-particularly mitogen-activated protein kinase (MAPK) signaling-in nitrogen mustard (NM)-induced corneal injury. In vitro, primary human corneal epithelial (P-HCECs), primary human corneal mesenchymal stromal cells (hcMSCs), and human corneal-limbal epithelial cell (HCLE) lines were exposed to varying concentrations of NM. The results demonstrated a dose-dependent increase in cellular senescence, characterized by reduced Ki67 expression, elevated p16, and p21 mRNA levels, as well as activation of the MAPK pathway activation. Treatment with a selective p38-MAPK inhibitor significantly reduced senescence markers and improved cell proliferation following exposure to NM. Overall, these studies indicate that NM exposure triggers cellular senescence and stress-related MAPK signaling, while p38-MAPK inhibition mitigates these effects, suggesting a potential therapeutic strategy.

Huanglian decoction prevents and treats radiation-induced intestinal injury in lung cancer by regulating endoplasmic reticulum stress.

Radiotherapy is a primary treatment method for lung cancer, and radiation-induced lung injury has been widely studied. However, the lung and intestines are closely related, and patients receiving lung radiotherapy often experience gastrointestinal reactions. Huanglian Decoction has proven effective in treating intestinal diseases, but its role in radiation-induced intestinal injury in lung cancer has not yet been demonstrated. The study investigated the potential protective mechanisms of Huanglian Decoction against radiation-induced intestinal injury in lung cancer. In vivo experiments were conducted to examine the morphological changes. Changes in endoplasmic reticulum stress-related proteins were assessed using electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. In vitro studies involved the overexpression of TRPA1 protein in NCM460 cells via lentiviral vectors. Tumor-bearing mice exhibited severe damage to both lung and colon tissues following radiotherapy, with elevated levels of IL-33, increased expression of ST2L and TRPA1 in colon tissues, higher levels of endoplasmic reticulum stress-related proteins, and the presence of apoptosis and inflammatory responses. Huanglian Decoction reduced radiation-induced intestinal injury by lowering IL-33 levels, which in turn reduced endoplasmic reticulum stress response in colon tissues. In TRPA1-overexpressing NCM460 cells, Huanglian Decoction decreased TRPA1 expression levels and significantly alleviated endoplasmic reticulum stress response. Conclusively, the results indicate that Huanglian Decoction alleviates radiation-induced intestinal endoplasmic reticulum stress by reducing IL-33 levels, subsequently inhibiting the expression of ST2L and TRPA1 in colon tissues. This demonstrates the protective effect of Huanglian Decoction on the intestines during lung cancer radiotherapy, highlighting its promising clinical application in radiation protection.

Oxidative and Endoplasmic Reticulum Stress Mediate Testicular Injury in a Rat Model of Varicocele.

Evidence of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) have been increasingly reported in varicocele (VCL)-affected testes. However, the mechanisms by which oxidative stress (OS) and ER stress contribute to male infertility in VCL remain unclear. In this study, male Sprague-Dawley rats were divided into a control group, which underwent sham surgery, and a VCL group, in which VCL was surgically induced. Eight weeks postoperatively, the VCL group exhibited significant testicular damage and sperm abnormalities. Western blot analysis revealed upregulation of ER stress-related proteins and downstream apoptotic markers in the VCL group. For further investigation, we developed an in vitro oxidative stress model using GC-2 cells treated with 400 µM hydrogen peroxide (H2O2) for 12h. Cells were also treated with either an ER stress inducer or inhibitor. We found that treatment with H2O2 and the ER stress inducer significantly reduced GC-2 cell viability and increased reactive oxygen species (ROS) production, ER stress, and apoptosis. Conversely, treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects. Our findings suggest a strong association between VCL-induced redox imbalance and ER stress-related injury driven by the UPR in this rat model. Furthermore, 4-PBA effectively reduced germ cell damage induced by ROS-mediated ER stress, offering potential therapeutic insights for treating VCL-related infertility.