O2 activation by subnanometer Re-Pt clusters supported on TiO2(110): exploring adsorption sites.

Activation of O2 by subnanometer metal clusters is a fundamental step in the reactivity and oxidation processes of single-cluster catalysts. In this work, we examine the adsorption and dissociation of O2 on RenPtm (n + m = 5) clusters supported on rutile TiO2(110) using DFT calculations. The adhesion energies of RenPtm clusters on the support are high, indicating significant stability of the supported clusters. Furthermore, the bimetallic Re-Pt clusters attach to the surface through the Re atoms. The oxygen molecule was adsorbed on three sites of the supported systems: the metal cluster, the surface, and the interface. At the metal cluster site, the O2 molecule binds strongly to RenPtm clusters, especially on the Re-rich clusters. O2 activation occurs by charge transfer from the metal atoms to the molecule. The dissociation of O2 on the RenPtm clusters is an exothermic process with low barriers. As a result, sub-nanometer Re-Pt clusters can be susceptible to oxidation. Similar results are obtained at the metal-support interface, where both the surface and cluster transfer charge to O2. To surface sites, molecular oxygen is adsorbed onto the Ti5c atoms with moderate adsorption energies. The polarons, which are produced by the interaction between the metal cluster and the surface, participate in the activation of the molecule. However, dissociating O2 in these sites is challenging due to the endothermic nature of the process and the high energy barriers involved. Our findings provide novel insights into the reactivity of supported clusters, specifically regarding the O2 activation by Re-Pt clusters on rutile TiO2(110).

Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells.

Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington's disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.

Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction.

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

polyamine uptake transporter 2 (put2) and decaying seeds enhance phyA-mediated germination by overcoming PIF1 repression of germination.

Red light promotes germination after activating phytochrome phyB, which destabilizes the germination repressor PIF1. Early upon seed imbibition, canopy light, unfavorable for photosynthesis, represses germination by stabilizing PIF1 after inactivating phyB. Paradoxically, later upon imbibition, canopy light stimulates germination after activating phytochrome phyA. phyA-mediated germination is poorly understood and, intriguingly, is inefficient, compared to phyB-mediated germination, raising the question of its physiological significance. A genetic screen identified polyamine uptake transporter 2 (put2) mutants that overaccumulate polyamines, a class of antioxidant polycations implicated in numerous cellular functions, which we found promote phyA-mediated germination. In WT seeds, our data suggest that canopy light represses polyamines accumulation through PIF1 while red light promotes polyamines accumulation. We show that canopy light also downregulates PIF1 levels, through phyA; however, PIF1 reaccumulates rapidly, which limits phyA-mediated germination. High polyamines levels in decaying seeds bypass PIF1 repression of germination and stimulate phyA-mediated germination, suggesting an adaptive mechanism promoting survival when viability is compromised.

Identification of tannic cell walls at the outer surface of the endosperm upon Arabidopsis seed coat rupture.

The seed coat is specialized dead tissue protecting the plant embryo from mechanical and oxidative damage. Tannins, a type of flavonoids, are antioxidants known to accumulate in the Arabidopsis seed coat and transparent testa mutant seeds, deficient in flavonoid synthesis, exhibit low viability. However, their precise contribution to seed coat architecture and biophysics remains evasive. A seed coat cuticle, covering the endosperm outer surface and arising from the seed coat inner integument 1 cell layer was, intriguingly, previously shown to be more permeable in transparent testa mutants deficient not in cuticular component synthesis, but rather in flavonoid synthesis. Investigating the role of flavonoids in cuticle permeability led us to identify periclinal inner integument 1 tannic cell walls being attached, together with the cuticle, to the endosperm surface upon seed coat rupture. Hence, inner integument 1 tannic cell walls and the cuticle form two fused layers present at the surface of the exposed endosperm upon seed coat rupture, regulating its permeability. Their potential physiological role during seed germination is discussed.

Embryonic Photosynthesis Affects Post-Germination Plant Growth.

Photosynthesis is the fundamental process fueling plant vegetative growth and development. The progeny of plants relies on maternal photosynthesis, via food reserves in the seed, to supply the necessary energy for seed germination and early seedling establishment. Intriguingly, before seed maturation, Arabidopsis (Arabidopsis thaliana) embryos are also photosynthetically active, the biological significance of which remains poorly understood. Investigating this system is genetically challenging because mutations perturbing photosynthesis are expected to affect both embryonic and vegetative tissues. Here, we isolated a temperature-sensitive mutation affecting CPN60α2, which encodes a subunit of the chloroplast chaperonin complex CPN60. When exposed to cold temperatures, cpn60α2 mutants accumulate less chlorophyll in newly produced tissues, thus allowing the specific disturbance of embryonic photosynthesis. Analyses of cpn60α2 mutants were combined with independent genetic and pharmacological approaches to show that embryonic photosynthetic activity is necessary for normal skoto- and photomorphogenesis in juvenile seedlings as well as long-term adult plant development. Our results reveal the importance of embryonic photosynthetic activity for normal adult plant growth, development, and health.

Towards establishing no observed adverse effect levels (NOAEL) for different sources of dietary phosphorus in feline adult diets: results from a 7-month feeding study.

High dietary phosphorus (P), particularly soluble salts, may contribute to chronic kidney disease development in cats. The aim of the present study was to assess the safety of P supplied at 1 g/1000 kcal (4184kJ) from a highly soluble P salt in P-rich dry format feline diets. Seventy-five healthy adult cats (n 25/group) were fed either a low P control (1·4 g/1000 kcal [4184kJ]; Ca:P ratio 0·97) or one of two test diets with 4 g/1000 kcal (4184 kJ); Ca:P 1·04 or 5 g/1000 kcal (4184kJ); Ca:P 1·27, both incorporating 1 g/1000 kcal (4184 kJ) sodium tripolyphosphate (STPP) - for a period of 30 weeks in a randomised parallel-group study. Health markers in blood and urine, glomerular filtration rate, renal ultrasound and bone density were assessed at baseline and at regular time points. At the end of the test period, responses following transition to a commercial diet (total P - 2·34 g/1000 kcal [4184kJ], Ca:P 1·3) for a 4-week washout period were also assessed. No adverse effects on general, kidney or bone (skeletal) function and health were observed. P and Ca balance, some serum biochemistry parameters and regulatory hormones were increased in cats fed test diets from week 2 onwards (P ≤ 0·05). Data from the washout period suggest that increased serum creatinine and urea values observed in the two test diet groups were influenced by dietary differences during the test period, and not indicative of changes in renal function. The present data suggest no observed adverse effect level for feline diets containing 1 g P/1000 kcal (4184 kJ) from STPP and total P level of up to 5 g/1000 kcal (4184 kJ) when fed for 30 weeks.

Horizontal-to-Vertical Spectral Ratio of Ambient Vibration Obtained with Hilbert-Huang Transform.

The Horizontal-to-Vertical Spectral Ratio (HVSR) of ambient vibration measurements is a common tool to explore near surface shear wave velocity (Vs) structure. HVSR is often applied for earthquake risk assessments and civil engineering projects. Ambient vibration signal originates from the combination of a multitude of natural and man-made sources. Ambient vibration sources can be any ground motion inducing phenomena, e.g., ocean waves, wind, industrial activity or road traffic, where each source does not need to be strictly stationary even during short times. Typically, the Fast Fourier Transform (FFT) is applied to obtain spectral information from the measured time series in order to estimate the HVSR, even though possible non-stationarity may bias the spectra and HVSR estimates. This problem can be alleviated by employing the Hilbert-Huang Transform (HHT) instead of FFT. Comparing 1D inversion results for FFT and HHT-based HVSR estimates from data measured at a well studied, urban, permanent station, we find that HHT-based inversion models may yield a lower data misfit χ2 by up to a factor of 25, a more appropriate Vs model according to available well-log lithology, and higher confidence in the achieved model.

Effects of a Peripherally Restricted Hybrid Inhibitor of CB1 Receptors and iNOS on Alcohol Drinking Behavior and Alcohol-Induced Endotoxemia.

Alcohol consumption is associated with gut dysbiosis, increased intestinal permeability, endotoxemia, and a cascade that leads to persistent systemic inflammation, alcoholic liver disease, and other ailments. Craving for alcohol and its consequences depends, among other things, on the endocannabinoid system. We have analyzed the relative role of central vs. peripheral cannabinoid CB1 receptors (CB1R) using a "two-bottle" as well as a "drinking in the dark" paradigm in mice. The globally acting CB1R antagonist rimonabant and the non-brain penetrant CB1R antagonist JD5037 inhibited voluntary alcohol intake upon systemic but not upon intracerebroventricular administration in doses that elicited anxiogenic-like behavior and blocked CB1R-induced hypothermia and catalepsy. The peripherally restricted hybrid CB1R antagonist/iNOS inhibitor S-MRI-1867 was also effective in reducing alcohol consumption after oral gavage, while its R enantiomer (CB1R inactive/iNOS inhibitor) was not. The two MRI-1867 enantiomers were equally effective in inhibiting an alcohol-induced increase in portal blood endotoxin concentration that was caused by increased gut permeability. We conclude that (i) activation of peripheral CB1R plays a dominant role in promoting alcohol intake and (ii) the iNOS inhibitory function of MRI-1867 helps in mitigating the alcohol-induced increase in endotoxemia.

ICE1 and ZOU determine the depth of primary seed dormancy in Arabidopsis independently of their role in endosperm development.

Seed dormancy is a widespread and key adaptive trait that is essential for the establishment of soil seed banks and prevention of pre-harvest sprouting. Herein we demonstrate that the endosperm-expressed transcription factors ZHOUPI (ZOU) and INDUCER OF CBF EXPRESSION1 (ICE1) play a role in determining the depth of primary dormancy in Arabidopsis. We show that ice1 or zou increases seed dormancy and the double mutant has an additive phenotype. This increased dormancy is associated with increased ABA levels, and can be separated genetically from any role in endosperm maturation because loss of ABA biosynthesis or DELAY OF GERMINATION 1 reverses the dormancy phenotype without affecting the aberrant seed morphology. Consistent with these results, ice1 endosperms had an increased capacity for preventing embryo greening, a phenotype previously associated with an increase in endospermic ABA levels. Although ice1 changes the expression of many genes, including some in ABA biosynthesis, catabolism and/or signalling, only ABA INSENSITIVE 3 is significantly misregulated in ice1 mutants. We also demonstrate that ICE1 binds to and inhibits expression of ABA INSENSITIVE 3. Our data demonstrate that Arabidopsis ICE1 and ZOU determine the depth of primary dormancy during maturation independently of their effect on endosperm development.

Spatially and genetically distinct control of seed germination by phytochromes A and B.

Phytochromes phyB and phyA mediate a remarkable developmental switch whereby, early upon seed imbibition, canopy light prevents phyB-dependent germination, whereas later on, it stimulates phyA-dependent germination. Using a seed coat bedding assay where the growth of dissected embryos is monitored under the influence of dissected endosperm, allowing combinatorial use of mutant embryos and endosperm, we show that canopy light specifically inactivates phyB activity in the endosperm to override phyA-dependent signaling in the embryo. This interference involves abscisic acid (ABA) release from the endosperm and distinct spatial activities of phytochrome signaling components. Under the canopy, endospermic ABA opposes phyA signaling through the transcription factor (TF) ABI5, which shares with the TF PIF1 several target genes that negatively regulate germination in the embryo. ABI5 enhances the expression of phytochrome signaling genes PIF1, SOMNUS, GAI, and RGA, but also of ABA and gibberellic acid (GA) metabolic genes. Over time, weaker ABA-dependent responses eventually enable phyA-dependent germination, a distinct type of germination driven solely by embryonic growth.

A Maternally Deposited Endosperm Cuticle Contributes to the Physiological Defects of transparent testa Seeds.

Mature dry seeds are highly resilient plant structures where the encapsulated embryo is kept protected and dormant to facilitate its ultimate dispersion. Seed viability is heavily dependent on the seed coat's capacity to shield living tissues from mechanical and oxidative stress. In Arabidopsis (Arabidopsis thaliana), the seed coat, also called the testa, arises after the differentiation of maternal ovular integuments during seed development. We recently described a thick cuticle tightly embedded in the mature seed's endosperm cell wall. We show here that it is produced by the maternal inner integument 1 layer and, remarkably, transferred to the developing endosperm. Arabidopsis transparent testa (tt) mutations cause maternally derived seed coat pigmentation defects. TT gene products encode proteins involved in flavonoid metabolism and regulators of seed coat development. tt mutants have abnormally high seed coat permeability, resulting in lower seed viability and dormancy. However, the biochemical basis of this high permeability is not fully understood. We show that the cuticles of developing tt mutant integuments have profound structural defects, which are associated with enhanced cuticle permeability. Genetic analysis indicates that a functional proanthocyanidin synthesis pathway is required to limit cuticle permeability, and our results suggest that proanthocyanidins could be intrinsic components of the cuticle. Together, these results show that the formation of a maternal cuticle is an intrinsic part of the normal integumental differentiation program leading to testa formation and is essential for the seed's physiological properties.

[Evaluation of endoscopic and histological activity as predictors of clinical relapse in ulcerative colitis]. / Evaluación de actividad endoscópica e histológica como predictores de recaída clínica en colitis ulcerativa.

Ulcerative colitis is a chronic inflammatory disease characterized by a recurrent and remitting course. Clinical remission and mucosal healing are the current therapeutic goals in management. The histological remission could be a better objective because of its prognostic impact. OBJECTIVE: To evaluate endoscopic and histological activity as predictors of clinical relapse in patients with ulcerative colitis. MATERIALS AND METHODS: Prospective descriptive study conducted from January 2015 to June 2018 at Guillermo Almenara Irigoyen National Hospital. Thirty-three patients diagnosed with ulcerative colitis who presented clinical remission after a flare were evaluated. Endoscopic remission was assessed (Mayo Score ≤1) after 6 months of follow- up with ileocolonoscopy and rectosigmoid biopsies. Histological remission was defined as score < 2 in the Simplified Geboes Score (SGS). Follow-up was performed for one year to observe relapses. RESULTS: 26 (78.8%) patients achieved endoscopic remission at 6 months (mean age 53 years, males 57.7%). Histological remission was observed in 69.2% (18/26). After 1 year of follow-up, 83.3% (15/18) of the patients who presented clinical, endoscopic and histological remission remained clinically asymptomatic. The RR of clinical relapse at one year was 3,18 (95% IC, 1,58-6,42, p=0,004) in patients without endoscopic remission and 4 (95% IC, 1,34-11,94, p=0,003) in patients without histological remission. CONCLUSIONS: Histological activity could be a better predictor of relapse compared to endoscopic remission, and should be the final therapeutic objective in the management of patients with ulcerative colitis.

Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer.

The kallikrein family comprises tissue kallikrein and 14 kallikrein-related peptidases (KLKs) recognized as a subgroup of secreted trypsin- or chymotrypsin-like serine proteases. KLKs are expressed in many cellular types where they regulate important physiological activities such as semen liquefaction, immune response, neural development, blood pressure, skin desquamation and tooth enamel formation. Tissue kallikrein, the oldest member and kinin-releasing enzyme, and KLK3/PSA, a tumor biomarker for prostate cancer are the most prominent components of the family. Additionally, other KLKs have shown an abnormal expression in neoplasia, particularly in breast cancer. Thus, increased levels of some KLKs may increase extracellular matrix degradation, invasion and metastasis; other KLKs modulate cell growth, survival and angiogenesis. On the contrary, KLKs can also inhibit angiogenesis and produce tumor suppression. However, there is a lack of knowledge on how KLKs are regulated in tumor microenvironment by molecules present at the site, namely cytokines, inflammatory mediators and growth factors. Little is known about the signaling pathways that control expression/secretion of KLKs in breast cancer, and further how activation of PAR receptors may contribute to functional activity in neoplasia. A better understanding of these molecular events will allow us to consider KLKs as relevant therapeutic targets for breast cancer.

Possible role of phytoestrogens in breast cancer via GPER-1/GPR30 signaling.

Estrogens generated within endocrine organs and the reproductive system act as ligands for at least three types of estrogen receptors. Estrogen receptors α (ERα) and ß (ERß) belong to the so-called classical family of estrogen receptors, whereas the G protein-coupled receptor GPR30, also known as GPER-1, has been described as a novel estrogen receptor sited in the cell membrane of target cells. Furthermore, these receptors are under stimulation of a family of exogenous estrogens, known as phytoestrogens, which are a diverse group of non-steroidal plant compounds derived from plant food consumed by humans and animals. Because phytoestrogens are omnipresent in our daily diet, they are becoming increasingly important in both human health and disease. Recent evidence indicates that in addition to classical estrogen receptors, phytoestrogens also activate GPER-1 a relevant observation since GPER-1 is involved in several physiopathological disorders and especially in estrogen-dependent diseases such as breast cancer.The first estrogen receptors discovered were the classical ERα and ERß, but from an evolutionary point of view G protein-coupled receptors trace their origins in history to over a billion years ago suggesting that estrogen receptors like GPER-1 may have been the targets of choice for ancient phytoestrogens and/or estrogens.This review provides a comprehensive and systematic literature search on phytoestrogens and its relationship with classical estrogen receptors and GPER-1 including its role in breast cancer, an issue still under discussion.

An Endosperm-Associated Cuticle Is Required for Arabidopsis Seed Viability, Dormancy and Early Control of Germination.

Cuticular layers and seeds are prominent plant adaptations to terrestrial life that appeared early and late during plant evolution, respectively. The cuticle is a waterproof film covering plant aerial organs preventing excessive water loss and protecting against biotic and abiotic stresses. Cutin, consisting of crosslinked fatty acid monomers, is the most abundant and studied cuticular component. Seeds are dry, metabolically inert structures promoting plant dispersal by keeping the plant embryo in an arrested protected state. In Arabidopsis thaliana seeds, the embryo is surrounded by a single cell endosperm layer itself surrounded by a seed coat layer, the testa. Whole genome analyses lead us to identify cutin biosynthesis genes as regulatory targets of the phytohormones gibberellins (GA) and abscisic acid (ABA) signaling pathways that control seed germination. Cutin-containing layers are present in seed coats of numerous species, including Arabidopsis, where they regulate permeability to outer compounds. However, the role of cutin in mature seed physiology and germination remains poorly understood. Here we identify in mature seeds a thick cuticular film covering the entire outer surface of the endosperm. This seed cuticle is defective in cutin-deficient bodyguard1 seeds, which is associated with alterations in endospermic permeability. Furthermore, mutants affected in cutin biosynthesis display low seed dormancy and viability levels, which correlates with higher levels of seed lipid oxidative stress. Upon seed imbibition cutin biosynthesis genes are essential to prevent endosperm cellular expansion and testa rupture in response to low GA synthesis. Taken together, our findings suggest that in the course of land plant evolution cuticular structures were co-opted to achieve key physiological seed properties.

Primary seed dormancy: a temporally multilayered riddle waiting to be unlocked.

Primary seed dormancy is an important adaptive plant trait whereby seed germination is blocked under conditions that would otherwise be favorable for germination. This trait is found in newly produced mature seeds of many species, but not all. Once produced, dry seeds undergo an aging time period, called dry after-ripening, during which they lose primary dormancy and gradually acquire the capacity to germinate when exposed to favorable germination conditions. Primary seed dormancy has been extensively studied not only for its scientific interest but also for its ecological, phenological, and agricultural importance. Nevertheless, the mechanisms underlying primary seed dormancy and its regulation during after-ripening remain poorly understood. Here we review the principal developmental stages where primary dormancy is established and regulated prior to and during seed after-ripening, where it is progressively lost. We attempt to identify and summarize what is known about the molecular and genetic mechanisms intervening over time in each of these stages.

Three-Dimensional Localized-Delocalized Anderson Transition in the Time Domain.

Systems which can spontaneously reveal periodic evolution are dubbed time crystals. This is in analogy with space crystals that display periodic behavior in configuration space. While space crystals are modeled with the help of space periodic potentials, crystalline phenomena in time can be modeled by periodically driven systems. Disorder in the periodic driving can lead to Anderson localization in time: the probability for detecting a system at a fixed point of configuration space becomes exponentially localized around a certain moment in time. We here show that a three-dimensional system exposed to a properly disordered pseudoperiodic driving may display a localized-delocalized Anderson transition in the time domain, in strong analogy with the usual three-dimensional Anderson transition in disordered systems. Such a transition could be experimentally observed with ultracold atomic gases.

Therapeutic Approaches in Mitochondrial Dysfunction, Proteolysis, and Structural Alterations of Diaphragm and Gastrocnemius in Rats With Chronic Heart Failure.

Patients with chronic heart failure (CHF) experience exercise intolerance, fatigue and muscle wasting, which negatively influence their survival. We hypothesized that treatment with either the antioxidant N-acetyl cysteine (NAC) or the proteasome inhibitor bortezomib of rats with monocrotaline-induced CHF may restore inspiratory and limb muscle mass, function, and structure through several molecular mechanisms involved in protein breakdown and metabolism in the diaphragm and gastrocnemius. In these muscles of CHF-cachectic rats with and without treatment with NAC or bortezomib (N = 10/group) and non-cachectic controls, proteolysis (tyrosine release, proteasome activities, ubiquitin-proteasome markers), oxidative stress, inflammation, mitochondrial function, myosin, NF-κB transcriptional activity, muscle structural abnormalities, and fiber morphometry were analyzed together with muscle and cardiac functions. In diaphragm and gastrocnemius of CHF-cachectic rats, tyrosine release, proteasome activity, protein ubiquitination, atrogin-1, MURF-1, NF-κB activity, oxidative stress, inflammation, and structural abnormalities were increased, while muscle and cardiac functions, myosin content, slow- and fast-twitch fiber sizes, and mitochondrial activity were decreased. Concomitant treatment of CHF-cachectic rats with NAC or bortezomib improved protein catabolism, oxidative stress, inflammation, muscle fiber sizes, function and damage, superoxide dismutase and myosin levels, mitochondrial function (complex I, gastrocnemius), cardiac function and decreased NF-κB transcriptional activity in both muscles. Treatment of CHF-cachectic animals with NAC or bortezomib attenuated the functional (heart, muscles), biological, and structural alterations in muscles. Nonetheless, future studies conducted in actual clinical settings are warranted in order to assess the potential beneficial effects and safety concerns of these pharmacological agents on muscle mass loss and wasting in CHF-cachectic patients.