The role of tissue persistent organic pollutants and genetic polymorphisms in patients with benign and malignant kidney tumors.

This study aimed to explore whether there is an association between environmental exposure to POPs and kidney tumor induction, and whether blood POP concentrations reflect kidney tissue concentrations. POP derivatives were determined in blood, tumor tissue, tumor surrounding tissue, and perirenal fat tissue samples taken from patients who underwent surgery for renal tumors. A voluntary control group was recruited for blood and urine samples as well. Urinary excretions of o,o'-dityrosine, chlorotyrosine, nitrotyrosine, and 8-OHdG were measured in the same patients. The possible role of genetic polymorphisms in CYP1A1, GST isozymes P, M, and T, and hOGG1 genes on the predisposition to renal cancer was investigated. Some POPs have been found to be associated with kidney cancer, as evidenced by their significantly high ORs. 8-OHdG levels were significantly higher compared to the control group. The GSTT1 null polymorphism can be a risk factor for malignant but not for benign kidney tumors.

Excitation of Reactive Oxygen Species and Damage to the Cell Membrane, Protein, and DNA are Important Inhibition Mechanisms of CO2 on Shewanella putrefaciens at 4 °C.

To explore whether oxidative stress caused by 100% CO2 is an inhibitory mechanism against Shewanella putrefaciens, the oxidative stress reaction, antioxidant activity, and damage to the cell membrane, protein, and DNA of CO2-incubated S. putrefaciens at 4 °C were evaluated. Research demonstrated that CO2 caused more severe reactive oxygen species (ROS) accumulation. Simultaneously, weaker •OH/H2O2/O2•--scavenging activity and decreased T-VOC and GSH content were also observed. The activities of antioxidant enzymes (SOD, POD, CAT, and GPX) continuously declined, which might be attributed to the CO2-mediated decrease in the pH value. Correspondingly, the cell membrane was damaged with hyperpolarization, increased permeability, and more severe lipid peroxidation. The expression of total and membrane protein decreased, and the synthesis and activity of extracellular protease were inhibited. DNA was also subjected to oxidative damage and expressed at a lower level. All results collaboratively confirmed that ROS excitation and inhibition of antioxidant activity were important inhibition mechanisms of CO2 on S. putrefaciens.

UPS-dependent strategies of protein quality control degradation.

The degradation of damaged proteins is critical for tissue integrity and organismal health because damaged proteins have a high propensity to form aggregates. E3 ubiquitin ligases are key regulators of protein quality control (PQC) and mediate the selective degradation of damaged proteins, a process termed 'PQC degradation' (PQCD). The degradation signals (degrons) that trigger PQCD are based on hydrophobic sites that are normally buried within the native protein structure. However, an open question is how PQCD-specialized E3 ligases distinguish between transiently misfolded proteins, which can be efficiently refolded, and permanently damaged proteins, which must be degraded. While significant progress has been made in characterizing degradation determinants, understanding the key regulatory signals of cellular and organismal PQCD pathways remains a challenge.

Oxidative stress, defective proteostasis and immunometabolic complications in critically ill patients.

Oxidative stress (OS) develops in critically ill patients as a metabolic consequence of the immunoinflammatory and degenerative processes of the tissues. These induce increased and/or dysregulated fluxes of reactive species enhancing their pro-oxidant activity and toxicity. At the same time, OS sustains its own inflammatory and immunometabolic pathogenesis, leading to a pervasive and vitious cycle of events that contribute to defective immunity, organ dysfunction and poor prognosis. Protein damage is a key player of these OS effects; it generates increased levels of protein oxidation products and misfolded proteins in both the cellular and extracellular environment, and contributes to forms DAMPs and other proteinaceous material to be removed by endocytosis and proteostasis processes of different cell types, as endothelial cells, tissue resident monocytes-macrophages and peripheral immune cells. An excess of OS and protein damage in critical illness can overwhelm such cellular processes ultimately interfering with systemic proteostasis, and consequently with innate immunity and cell death pathways of the tissues thus sustaining organ dysfunction mechanisms. Extracorporeal therapies based on biocompatible/bioactive membranes and new adsorption techniques may hold some potential in reducing the impact of OS on the defective proteostasis of patients with critical illness. These can help neutralizing reactive and toxic species, also removing solutes in a wide spectrum of molecular weights thus improving proteostasis and its immunometabolic corelates. Pharmacological therapy is also moving steps forward which could help to enhance the efficacy of extracorporeal treatments. This narrative review article explores the aspects behind the origin and pathogenic role of OS in intensive care and critically ill patients, with a focus on protein damage as a cause of impaired systemic proteostasis and immune dysfunction in critical illness.

Shock and Temperature Monitoring During Transport of Immunoglobulins from a Hospital to Patients' Homes: A Pilot Study.

Transport of biopharmaceuticals from a hospital to a patient's home is scarcely researched but it is essential to investigate the effects of such transport on the stability of the drug, before home-based care can take place. In this study, transport of biopharmaceuticals in vials that are marketed as ready-to-administer from a hospital pharmacy to patients' homes was investigated. Immunoglobulin packages were tracked with 10 G and 25 G shock indicators and temperature data loggers. In the control group, immunoglobulins were transported from the hospital pharmacy to the outpatient daycare unit. During the transport process to patients' homes (n = 39), almost half of the packages were shocked with 25 G and more than half of all packages exceeded the required temperature range. Fortunately, the results found do not affect the stability of the ready-to-administer vials with immunoglobulins. However, these results indicate that the transport of biopharmaceuticals should be better controlled as not all biopharmaceuticals or formulations are so stable. Therefore, results of this pilot study provide a basis for recommendations for home-based therapy.

Laser Ablation-Generated Crystalline Selenium Nanoparticles Prevent Damage of DNA and Proteins Induced by Reactive Oxygen Species and Protect Mice against Injuries Caused by Radiation-Induced Oxidative Stress.

With the help of laser ablation, a technology for obtaining nanosized crystalline selenium particles (SeNPs) has been created. The SeNPs do not exhibit significant toxic properties, in contrast to molecular selenium compounds. The administration of SeNPs can significantly increase the viabilities of SH-SY5Y and PCMF cells after radiation exposure. The introduction of such nanoparticles into the animal body protects proteins and DNA from radiation-induced damage. The number of chromosomal breaks and oxidized proteins decreases in irradiated mice treated with SeNPs. Using hematological tests, it was found that a decrease in radiation-induced leukopenia and thrombocytopenia is observed when selenium nanoparticles are injected into mice before exposure to ionizing radiation. The administration of SeNPs to animals 5 h before radiation exposure in sublethal and lethal doses significantly increases their survival rate. The modification dose factor for animal survival was 1.2. It has been shown that the introduction of selenium nanoparticles significantly normalizes gene expression in the cells of the red bone marrow of mice after exposure to ionizing radiation. Thus, it has been demonstrated that SeNPs are a new gene-protective and radioprotective agent that can significantly reduce the harmful effects of ionizing radiation.

Antioxidant, Anti-Inflammatory, Antimicrobial, and Anticancer Activities of Pomegranate Juice Concentrate.

Pomegranate juice concentrate (PJC) is a rich source of polyphenols, which exhibit significant antioxidant activity and potential health benefits for disease prevention and therapy. In this study, the polyphenolic profile of PJC was investigated for the first time, and it was found that PJC can inhibit oxidative damage to bovine serum albumin (BSA) and deoxyribonucleic acid (DNA), as well as acetylcholinesterase, α-amylase, and tyrosinase activities. The primary polyphenols identified in PJC were 4-Hydroxy-3-Methoxybenzoate, epicatechin, catechin, rutin, ferulic acid, P-coumaric acid, and cinnamic acid. Additionally, PJC demonstrated potent antibacterial effects against human pathogens such as Streptococcus mutans and Aeromonas hydrophila and dose-dependently reduced the proliferation of colorectal, breast, and hepatic cancer cells via apoptosis. Furthermore, PJC blocked B-cell lymphoma 2 (BCl-2) and the expression of a potent cyclin-dependent kinase inhibitor (P21) and enhanced tumor protein (P53) expression, compared to both untreated cells and cells treated with fluoropyrimidine 5-fluorouracil (5-FU). As a result, PJC may be a beneficial ingredient in the formulation of emerging natural-compound-based chemotherapy and functional foods and could be utilized by the food, nutraceutical, and pharmaceutical industries.

Superiority of UV222 radiation by in situ aquatic electrode KrCl excimer in disinfecting waterborne pathogens: Mechanism and efficacy.

Microbial safety in water has always been the focus of attention, especially during the COVID-19 pandemic. Development of green, efficient and safe disinfection technology is the key to control the spread of pathogenic microorganisms. Here, an in situ aquatic electrode KrCl excimer radiation with main emission wavelength 222 nm (UV222) was designed and used to disinfect model waterborne virus and bacteria, i.e. phage MS2, E. coli and S. aureus. High inactivation efficacy and diversity of inactivation mechanisms of UV222 were proved by comparision with those of commercial UV254. UV222 could totally inactivate MS2, E. coli and S. aureus with initial concentrations of ∼107 PFU or CFU mL-1 within 20, 15, and 36 mJ/cm2, respectively. The UV dose required by UV254 to inactivate the same logarithmic pathogenic microorganism is at least twice that of UV222. The protein, genomic and cell membrane irreparable damage contributed to the microbial inactivation by UV222, but UV254 only act on nucleic acid of the target microorganisms. We found that UV222 damage nucleic acid with almost the same or even higher efficacy with UV254. In addition, free base damage of UV222 in similar ways with UV254(dimer and hydrate). But due to the quantum yield of free base degradation of UV222 was greater than UV254, the photolysis rates of UV222 to A, G, C and U four bases were 11.5, 1.2, 3.2 and 1 times as those of UV254, respectively. Excellent disinfection performance in UV222 irradiation was also achieved in real water matrices (WWTP and Lake). In addition, it was proved that coexisting HCO3- or HPO42 - in real and synthetic water matrices can produce • OH to promote UV222 disinfection. This study provided novel insight into the UV222 disinfection process and demonstrated its possibility to take place of the conventional ultraviolet mercury lamp in water purification.

Proteostasis in ice: the role of heat shock proteins and ubiquitin in the freeze tolerance of the intertidal mussel, Mytilus trossulus.

The bay mussel, Mytilus trossulus, is an animal that can survive extracellular ice formation. Depending on air and ocean temperatures, freeze tolerant intertidal organisms, like M. trossulus, may freeze and thaw many times during the winter. Freezing can cause protein denaturation, leading to an induction of the heat shock response with expression of chaperone proteins like the 70 kDa heat shock protein (HSP70), and an increase in ubiquitin-conjugated proteins. There has been little work on the mechanisms of freeze tolerance in intertidal species, limiting our understanding of this survival strategy. Additionally, this limited research has focused solely on the effects of single freezing events, but the act of repeatedly crossing the freezing threshold may present novel physiological or biochemical stressors that have yet to be discovered. Mytilus are important ecosystem engineers and provide habitat for other intertidal species, thus understanding their physiology under thermal extremes is important for preserving shoreline health. We predicted that repeated freeze exposures would increase mortality, upregulate HSP70 expression, and increase ubiquitin conjugates in mussels, relative to single, prolonged freeze exposures. Mytilus trossulus from Vancouver, Canada were repeatedly frozen for a combination of 1 × 8 h, 2 × 4 h, or 4 × 2 h. We then compared mortality, HSP70 expression, and the quantity of ubiquitin-conjugated proteins across experimental groups. We found a single 8-h freeze caused significantly more mortality than repeated freeze-thaw cycles. We also found that HSP70 and ubiquitinated protein was upregulated exclusively after freeze-thaw cycles, suggesting that freeze-thaw cycles offer a period of damage repair between freezes. This indicates that freeze-thaw cycles, which happen naturally in the intertidal, are crucial for M. trossulus survival in sub-zero temperatures.

Investigation on the Toxicity of Nanoparticle Mixture in Rainbow Trout Juveniles.

The environmental impacts of nanoparticle mixtures in the aquatic environment is not well understood. The purpose of this study examined the sub-lethal toxicity of low concentrations (ug/L range) of selected nanoparticles alone and in mixtures in juvenile trout. Fish were exposed to to individual and two environmentally relevant mixtures of silver (nAg), copper oxide (nCuO) and cerium oxide (nCeO) nanoparticles for 96 h at 15 °C. After the exposure period, fish were depurated overnight and tissue levels in Ag, Ce, Cu and Zn were determined along with a suite of effects biomarkers such as oxidative stress/inflammation, denatured protein tagging (ubiquitin), DNA strand breaks (genotoxicity) and acetylcholinesterase (AChE) activity. The data showed that these nanoparticles behaved as suspended matter but were nevertheless bioavailable for fish with bioconcentration factors of 6, 8 and 2 for nAg, nCeO and nCuO respectively. Only nCuO alone increased malonaldehyde (lipid peroxidation) contents but all nanoparticles increased DNA damage, protein-ubiquitin labeling, and decreased AChE activity. Globally, the toxicity of nCeO and nCuO was generally stronger than nAg, and antagonist effects were found in the mixtures. The interactions involved in these antagonisms are not well understood but do not involve the liberation of free ions and labile zinc in tissues. In conclusion, the bioavailability and toxicity of these nanoparticles are influenced by mixtures of nanoparticles, which is likely to occur in contaminated environments.

Cereblon neo-substrate binding mimics the recognition of the cyclic imide degron.

In targeted protein degradation, immunomodulatory drugs (IMiDs) or cereblon (CRBN) E3 ligase modulatory drugs (CELMoDs) recruit neo-substrate proteins to the E3 ubiquitin ligase receptor CRBN for ubiquitination and subsequent proteasomal degradation. While the structural basis of this mechanism is generally understood, we have only recently described the recognition mode of the natural CRBN degron. In this communication, we reveal that the IMiD- or CELMoD-mediated binding of neo-substrates closely mimics the recognition of natural degrons. In crystal structures, we identify a conserved binding mode for natural degron peptides with an elaborate hydrogen bonding network involving the backbone of each of the six C-terminal degron residues, without the involvement of side chains. In a structural comparison, we show that neo-substrates recruited by IMiDs or CELMoDs emulate every single hydrogen bond of this network and thereby explain the origins of the largely sequence-independent recognition of neo-substrates. Our results imply that the V388I substitution in CRBN does not impair natural degron recognition and complete the structural basis for the rational design of CRBN effectors.

Tocopherol-assisted magnetic Ag-Fe3O4-TiO2 nanocomposite for photocatalytic bacterial-inactivation with elucidation of mechanism and its hazardous level assessment with zebrafish model.

In recent years, many endeavours have been prompted with photocatalytic nanomaterials by the need to eradicate pathogenic microorganisms from water bodies. Herein, a tocopherol-assisted Ag-Fe3O4-TiO2 nanocomposite (TAFTN) was synthesized for photocatalytic bacterial inactivation. The prepared TAFTN became active under sunlight due to its narrowed bandgap, inactivating the bacterial contaminants via photo-induced ROS stress. The ROS radicals destroy bacteria by creating oxidative stress, which damages the cell membrane and cellular components such as nucleic acids and proteins. For the first time, the nano-LC-MS/MS-based quantitative proteomics reveals that the disrupted proteins are involved in a variety of cellular functions; the most of these are involved in the metabolic pathway, eventually leading to bacterial death during TAFTN-photocatalysis under sunlight. Furthermore, the toxicity analysis confirmed that the inactivated bacteria seemed to have no detrimental impact on zebrafish model, showing that the disinfected water via TAFTN-photocatalysis is enormously safe. Furthermore, the TAFTN-photocatalysis successfully killed the bacterial cells in natural seawater, indicating the consistent photocatalytic efficacy when recycled repeatedly. The results of this work demonstrate that the produced nanocomposite might be a powerful recyclable and sunlight-active photocatalyst for environmental water treatment.

Oxidative Damage by 3-nitrotyrosine in Young Adults with Obesity: Its Implication in Chronic and Contagious Diseases.

INTRODUCTION: Cellular damage by oxidation occurs in numerous chronic diseases, such as obesity, type II diabetes, cardiovascular disease, nonalcoholic fatty liver, etc. The oxidized compound 3-nitrotyrosine is a marker of oxidative stress and protein oxidation damage. OBJECTIVE: The article aims to assess whether 3-nitrotyrosine levels are higher in young people with obesity than in the same population without obesity. METHODS: Anthropometry and blood chemistry analyses were performed on 24 young Mexican participants (18-30 years old), categorized into two groups based on their waist circumference: Withobesity (≥ 80 cm women; ≥ 90 cm men) and without-obesity (<80 cm women; <90 cm men). Additionally, 3-nitrotyrosine blood values were quantified by ELISA. RESULTS: Except for HDL-cholesterol, the mean values of lipids increased in women and men with obesity (p<0.05), and 3-nitrotyrosine concentration (nM/µg total protein) was higher by 60% in the group with-obesity compared to the group without-obesity, both for women (66.21 ± 23.85 vs. 40.69 ± 16.25, p<0.05) and men (51.72 ± 20.56 vs. 30.52 ± 5.21, p<0.05). CONCLUSION: Oxidative damage measured by compound 3-nitrotyrosine was higher in the group with obesity than in the group without obesity, which, if not controlled, could lead to a chronic oxidative condition and thereby to a degree of cellular aging with adverse health effects.

Identification and structural basis of C-terminal cyclic imides as natural degrons for cereblon.

Cereblon (CRBN) is a ubiquitously expressed E3 ligase substrate receptor and a key player in pharmaceutical targeted protein degradation. Despite substantial insight gained into its chemical ligand space that is exploited in small-molecule protein degraders, its cellular role and native mechanism of substrate recognition remained elusive so far. In this communication, we report the discovery of C-terminal aspartimide and aminoglutarimide residues as natural degron motifs that are recognized by CRBN with high specificity. These C-terminal cyclic imides are known to form in ageing proteins as a result of spontaneous chain breaks after an attack of an asparagine or glutamine side chain amide on the adjacent peptide bond, and thereby mark potentially malfunctional protein fragments. In crystal structures, we uncover that these C-terminal cyclic imides are bound in the same fashion as small-molecule CRBN modulators, and that the residues preceding the cyclic terminus contribute to the interaction with a sequence-unspecific backbone hydrogen bonding pattern with strictly conserved residues in CRBN. We postulate that C-terminal aspartimide and aminoglutarimide residues resulting from chain breaks are largely underappreciated protein damages and represent the native degrons of CRBN.

Effect of Laser-Induced Optical Breakdown on the Structure of Bsa Molecules in Aqueous Solutions: An Optical Study.

The influence of laser radiation of a typical surgical laser on the physicochemical properties of the Bovine Serum Albumin (BSA) protein was studied. It was established that the physicochemical characteristics of optical breakdown weakly depend on the concentration of protein molecules. At the same time, the patterns observed for an aqueous solution of BSA irradiated with a laser for different time periods were extremely similar to the classical ones. It was established that after exposure to laser radiation, the optical density of protein solutions increases. At the same time, the intensity of BSA fluorescence due to aromatic amino acid residues decreases insignificantly after exposure to laser radiation. In this case, the position of the excitation and emission maximum does not change, and the shape of the fluorescence spot on 3D maps also does not change significantly. On the Raman spectrum after exposure to laser radiation, a significant decrease in 1570 cm-1 was observed, which indicates the degradation of α-helices and, as a result, partial denaturation of BSA molecules. Partial denaturation did not significantly change the total area of protein molecules, since the refractive index of solutions did not change significantly. However, in BSA solutions, after exposure to laser radiation, the viscosity increased, and the pseudoplasticity of aqueous solutions decreased. In this case, there was no massive damage to the polypeptide chain; on the contrary, when exposed to optical breakdown, intense aggregation was observed, while aggregates with a size of 400 nm or more appeared in the solution. Thus, under the action of optical breakdown induced by laser radiation in a BSA solution, the processes of partial denaturation and aggregation prevail, aromatic amino acid residues are damaged to a lesser extent, and fragmentation of protein molecules is not observed.

Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway-A Plausible Mechanism of Nickel Toxicity.

Nickel is toxic to humans. Its compounds are carcinogenic. Furthermore, nickel allergy is a severe health problem that affects approximately 10-20% of humans. The mechanism by which these conditions develop remains unclear, but it may involve the cleavage of specific proteins by nickel ions. Ni(II) ions cleave the peptide bond preceding the Ser/Thr-Xaa-His sequence. Such sequences are present in all four enzymes of the melatonin biosynthesis pathway, i.e., tryptophan 5-hydroxylase 1, aromatic-l-amino-acid decarboxylase, serotonin N-acetyltransferase, and acetylserotonin O-methyltransferase. Moreover, fragments prone to Ni(II) are exposed on surfaces of these proteins. Our results indicate that all four studied fragments undergo cleavage within tens of hours at pH 8.2 and 37 °C, corresponding with the conditions in the mitochondrial matrix. Since melatonin, a potent antioxidant and anti-inflammatory agent, is synthesized within the mitochondria of virtually all human cells, depleting its supply may be detrimental, e.g., by raising the oxidative stress level. Intriguingly, Ni(II) ions have been shown to mimic hypoxia through the stabilization of HIF-1α protein, but melatonin prevents the action of HIF-1α. Considering all this, the enzymes of the melatonin biosynthesis pathway seem to be a toxicological target for Ni(II) ions.

Markers of oxidative stress in postmenopausal women with metabolic syndrome.

During the postmenopausal period, there are metabolic alterations that predispose individuals to metabolic syndrome (MS), oxidative stress (OS), and the risk of developing cardiovascular diseases. We aimed to compare the concentrations of OS markers in postmenopausal women with and without MS. Malondialdehyde, carbonyl groups, and total antioxidant capacity (TAC) were quantified. We conducted a cross-sectional study: Group 1 (n = 42) included women without MS, and Group 2 (n = 58) comprised women with MS. Participants' age was similar between groups. Glucose, insulin, the homeostasis model assessment of insulin resistance, triglycerides, uric acid, and body mass index were significantly lower in postmenopausal women without MS. OS markers were significantly lower in Group 1 vs. Group 2: malondialdehyde, 31.32 ± 14.93 vs. 40.27 ± 17.62 pmol MDA/mg dry weight (p = .01); protein carbonylation, 6325 ± 1551 vs. 7163 ± 1029 pmol PC/mg protein (p = .0003); and TAC, 1497 ± 297.3 vs. 1619 ± 278.8 pmol Trolox equivalent/mg protein (p = .041). OS markers were significantly higher in postmenopausal women with MS. Impact statementWhat is already known on this subject? Oxidative stress has been implicated in numerous disease processes; however, information on the relationship between oxidative stress and metabolic syndrome among postmenopausal women remains limited.What do the results of this study add? Our results indicate that in postmenopausal Mexican women, oxidative stress markers were significantly lower in those without metabolic syndrome, whereas total antioxidant capacity was higher in those with metabolic syndrome, which could be explained as an antioxidant defense mechanism capable of neutralising excess oxidative damage markers.What are the implications of these findings for clinical practice and/or further research? This study is of interest to a broad audience because it compares the concentrations of oxidative stress markers in postmenopausal women with and without metabolic syndrome. Our study could support intervention with supplements or foods rich in antioxidants as lifestyle modifications in postmenopausal women with metabolic syndrome.

Severe ethanol stress induces the preferential synthesis of mitochondrial disaggregase Hsp78 and formation of DUMPs in Saccharomyces cerevisiae.

Severe ethanol stress (>9% v/v) induces pronounced translation repression in yeast cells. However, some proteins, which are exceptionally synthesized even under translation repression, play important roles in ethanol tolerance. These proteins are expected to provide important clues for elucidating the survival strategies of yeast cells under severe ethanol stress. In this study, we identified Hsp78 as a protein effectively synthesized under severe ethanol stress. As Hsp78 is involved in mitochondrial protein quality control, we investigated the effect of severe ethanol stress on mitochondrial proteins and found that Ilv2, Kgd1, and Aco1 aggregated with Hsp78 under severe ethanol stress, forming mitochondrial deposition sites for denatured proteins, called DUMPs (Deposits of Unfolded Mitochondrial Proteins). Aggregation of mitochondrial proteins and formation of DUMPs were accelerated in hsp78∆ cells compared with those in wild-type cells. During the recovery process after ethanol removal, aggregated Ilv2 and DUMP levels rapidly decreased in wild-type cells but were maintained for a long time (>180 min) in hsp78Δ cells. Furthermore, the frequency of respiration-deficient mutants caused by severe ethanol stress was higher in hsp78∆ cells than in wild-type cells. These results indicate that severe ethanol stress damaged mitochondrial proteins and that Hsp78 was preferentially synthesized to cope with the damage, thereby suppressing the rapid increase in aggregated protein levels under stress and achieving proper clearance of aggregated proteins during the recovery process. This study provides novel insights into the adverse effects of ethanol on mitochondria and yeast response to severe ethanol stress.

Impaired proteostasis in obese skeletal muscle relates to altered immunoproteasome activity.

Obesity-associated inflammation and/or oxidative stress can damage intramuscular proteins and jeopardize muscle integrity. The immunoproteasome (iProt) is vital to remove oxidatively modified proteins, but this function may be compromised with obesity. We sought to elucidate whether diet-induced obesity alters intramuscular iProt content and activity in mice to identify a possible mechanism for impaired muscle proteostasis in the obese state. Total proteasome content and activity and estimates of muscle oxidative damage, inflammation, muscle mass and strength were also assessed. Twenty-three male, 5-week-old C57BL/6J mice were fed a high-fat, high-sucrose (HFS; 45% kcal fat, 17% sucrose, n = 12) or low-fat, low-sucrose (LFS; 10% kcal fat, 0% sucrose, n = 11) diet for 12 weeks. Strength was assessed via a weightlifting test. Despite no change in pro-inflammatory cytokines (P > 0.05), oxidative protein damage was elevated within the gastrocnemius (P = 0.036) and tibialis anterior (P = 0.033) muscles of HFS-fed mice. Intramuscular protein damage coincided with reduced iProt and total proteasome activity (P < 0.05), and reductions in relative muscle mass (P < 0.001). Therefore, proteasome dysregulation occurs in obese muscle and may be a critical link in muscle oxidative stress. Novelty: Our results show for the first time that immunoproteasome and total proteasome function is significantly reduced within obese muscle. Visceral fat mass is a significant predictor of diminished proteasome activity in skeletal muscle. Proteasome function is inversely correlated with an intramuscular accumulation of oxidatively damaged proteins.

The Life Span and Levels of Oxidative Stress in Foragers Between Feral and Managed Honey Bee Colonies.

Molecular damage caused by oxidative stress may lead to organismal aging and result in acute mortality to organisms. Thus, oxidative stress resistance and longevity are closely linked. Honey bees (Apis mellifera) are the most important managed pollinator in agriculture, but the long-term survival of honey bees is seriously threatened. Feral honey bee colonies can be used as natural resources to improve honey bee health. One question we ask here is whether feral honey bees are stress resistant or survive longer than managed bee populations. More work is needed to determine the impact of oxidative stress on honey bee health and survival. In this study, we used paired colony designs to compare the life span of worker bees (foragers) between feral and managed colonies and their levels of oxidative stress. Each pair of colonies shared similar foraging resources. The results indicated that foragers in feral colonies had longer survival times and life spans than those in managed colonies. The levels of oxidative stress from lipid damage content in feral colonies were higher than those in managed colonies, indicating that they used a tolerance mechanism rather than a repair mechanism to survive. Our study provides new insights into a colony difference in the physiology and oxidative stress resistance of feral honey bees compared with managed colony stocks.