Deleterious Changes Research Articles

Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.

Approximately 10%-15% of couples worldwide are infertile, and male factors account for approximately half of these cases. Teratozoospermia is a major cause of male infertility. Although various mutations have been identified in teratozoospermia, these can vary among ethnic groups. In this study, we performed whole-exome sequencing to identify genetic changes potentially causative of teratozoospermia. Out of seven genes identified, one, ATP/GTP Binding Protein 1 (AGTPBP1), was characterized, and three missense changes were identified in two patients (Affected A: p.Glu423Asp and p.Pro631Leu; Affected B: p.Arg811His). In those two cases, severe sperm head and tail defects were observed. Moreover, AGTPBP1 localization showed a fragmented pattern compared to control participants, with specific localization in the neck and annulus regions. Using murine models, we found that AGTPBP1 is localized in the manchette structure, which is essential for sperm structure formation. Additionally, in Agtpbp1-null mice, we observed sperm head and tail defects similar to those in sperm from AGTPBP1-mutated cases, along with abnormal polyglutamylation tubulin and decreasing △-2 tubulin levels. In this study, we established a link between genetic changes in AGTPBP1 and human teratozoospermia for the first time and identified the role of AGTPBP1 in deglutamination, which is crucial for sperm formation.

Arginine and Lysine Supplementation Potentiates the Beneficial β-Hydroxy ß-Methyl Butyrate (HMB) Effects on Skeletal Muscle in a Rat Model of Diabetes.

Skeletal muscle is the key tissue for maintaining protein and glucose homeostasis, having a profound impact on the development of diabetes. Diabetes causes deleterious changes in terms of loss of muscle mass, which will contribute to reduced glucose uptake and therefore progression of the disease. Nutritional approaches in diabetes have been directed to increase muscle glucose uptake, and improving protein turnover has been at least partially an oversight. In muscle, β-hydroxy β-methyl butyrate (HMB) promotes net protein synthesis, while arginine and lysine increase glucose uptake, albeit their effects on promoting protein synthesis are limited. This study evaluates if the combination of HMB, lysine, and arginine could prevent the loss of muscle mass and function, reducing the progression of diabetes. Therefore, the combination of these ingredients was tested in vitro and in vivo. In muscle cell cultures, the supplementation enhances glucose uptake and net protein synthesis due to an increase in the amount of GLUT4 transporter and stimulation of the insulin-dependent signaling pathway involving IRS-1 and Akt. In vivo, using a rat model of diabetes, the supplementation increases lean body mass and insulin sensitivity and decreases blood glucose and serum glycosylated hemoglobin. In treated animals, an increase in GLUT4, creatine kinase, and Akt phosphorylation was detected, demonstrating the synergic effects of the three ingredients. Our findings showed that nutritional formulations based on the combination of HMB, lysine, and arginine are effective, not only to control blood glucose levels but also to prevent skeletal muscle atrophy associated with the progression of diabetes.

Telomeres as hotspots for innate immunity and inflammation

Aging is marked by the gradual accumulation of deleterious changes that disrupt organ function, creating an altered physiological state that is permissive for the onset of prevalent human diseases. While the exact mechanisms governing aging remain a subject of ongoing research, there are several cellular and molecular hallmarks that contribute to this biological process. This review focuses on two factors, namely telomere dysfunction and inflammation, which have emerged as crucial contributors to the aging process. We aim to discuss the mechanistic connections between these two distinct hallmarks and provide compelling evidence highlighting the loss of telomere protection as a driver of pro-inflammatory states associated with aging. By reevaluating the interplay between telomeres, innate immunity, and inflammation, we present novel perspectives on the etiology of aging and its associated diseases.

The Skin and Inflamm-Aging.

With its unique anatomical location facing both the external and internal environment, the skin has crucial functions, including shielding the body from damage caused by ultraviolet radiation and chemicals, preventing water loss, acting as a primary barrier against pathogens, participating in metabolic processes like vitamin D production and temperature control and relaying information to the body through sensory and proprioceptor nerves. Like all organ systems, skin is known to undergo multiple changes with aging. A better understanding of the mechanisms that mediate aging-related skin dysfunction may allow the creation of targeted therapeutics that have beneficial effects not only on aged skin but also on other organs and tissues that experience a loss of or decline in function with aging. The skin is the largest organ of the body and can contribute to serum inflammatory mediator levels. One alteration known to occur with age is an impairment of skin barrier function; since disruption of the barrier is known to induce inflammation, skin may be a major contributor to the sustained, sub-clinical systemic inflammation associated with aging. Such "inflamm-aging" may underlie many of the deleterious changes observed in aged individuals. This review explores the role of age-related skin changes, skin inflammation and inflamm-aging.

Probiotics as a therapeutic approach in colorectal cancer.

Colorectal cancer (CRC) is a growing concern worldwide. In recent decades, the incidence of CRC has increased, and this has been attributed to changes in lifestyle. The lack of physical activity, smoking habits, and a diet high in red meat and fat and low in fiber are important aspects of these deleterious changes in lifestyle. The increase in the incidence of CRC has impelled researchers to investigate methods for preventing and treating CRC with greater efficacy and fewer complications. Probiotics are an attractive and potentially promising therapeutic approach. They have been evaluated by a large number of preclinical and clinical studies in recent years, and it has been found that they can play a role in the prevention, treatment, and management of complications of CRC. This review provides a concise summary of the mechanisms of action of probiotics. Furthermore, it focuses on the results of clinical and preclinical studies that evaluated probiotics' effects on CRC management. It also discusses the effects of different strains of probiotics and their combination in CRC treatment.

Níveis de gordura inerte de palma na ração para cabritos – avaliação de desempenho produtivo e comportamento ingestivo

Fat sources represent an important component in ruminant feed, as they provide 2.25 times more energy than carbohydrates, and new sources, such as inert fats from rumen degradation, are a good option due to their fatty acid profile. The objective was to evaluate the performance and ingestive behavior of goats fed increasing levels of inert palm fat in the diet. Sixteen goats were used, distributed in an entirely randomized design, dairy crossbred, entire males, with initial ages of 60 days and 18.66 kg of live weight. The experiment was conducted in an entirely randomized design with repeated measures in time, with four treatments: 0, 25, 50 and 75 grams of inert palm fat per head and four repetitions per treatment. Dry matter (DM), mineral matter (MML) and organic matter (OML) intake was evaluated, and morphometric measurements of treatments and periods were compared by regression study (P<0.05). The evaluations of weight gain were done weekly and the biometric measures, ECC and evaluation of ingestive behavior, fortnightly until the end of the experiment, which lasted 60 days. Only the treatment with the lowest inclusion of inert palm fat kept the DMC below the recommended by the NRC (2007). There was no statistical difference (P>0.05) for average daily gain, weight gain, biometric variables and ingestive behavior as palm inert fat was included in the diet of goats. For the presented ECC data it is noted that it was significant (P<0.05) and increasing keeping within the range for the category. Therefore, it is noted that the use of inert palm fat supplied at different levels did not promote deleterious changes in dry matter intake, morphometric measurements and ingestive behavior.

The influence of light on elasmobranch behavior and physiology: a review

In this review, we summarize the state of knowledge of the influence of light on the activity and physiology of elasmobranchs (sharks, skates, rays, and sawfish). These are a diverse group with great economic and ecological importance. The long-term success of a species is largely determined by its ability to respond to changes in its environment. Light plays an important role for many marine species in signaling rhythmic environmental changes which are part of daily and annual cycles. Behavioral and physiological changes by organisms in response to these signals have evolved enabling them to maximize survival and reproductive success. In an environment with increased levels of artificial light at night (ALAN), deleterious changes in activity and physiology can occur. By summarizing what is known about the influence of light on elasmobranch activity, it can be concluded that ALAN is likely to have a negative impact on elasmobranchs at the individual and population level. We also discuss the example of intentional nocturnal light pooling by the tourism industry to attract whale sharks (Rhincodon typus) and manta rays (Mobula spp.) and recommend regulation of this activity.

Physical Activity Associates with T1rho MRI of Femoral Cartilage After Anterior Cruciate Ligament Reconstruction.

Less physical activity has been associated with systemic biomarkers of cartilage breakdown after anterior cruciate ligament reconstruction (ACLR). However, previous research lacks analysis of deleterious cartilage compositional changes and objective physical activity after ACLR. The purpose of this study was to determine the association between physical activity quantified via accelerometer-based measures of daily steps and time in moderate-to-vigorous physical activity (MVPA), and T1rho magnetic resonance imaging (MRI) of the femoral articular cartilage, a marker of proteoglycan density in individuals with ACLR. Daily steps and MVPA were assessed over 7 d using an accelerometer worn on the hip in 26 individuals between 6 and 12 months after primary unilateral ACLR. Resting T1rho MRI was collected bilaterally, and T1rho MRI interlimb ratios (ILR: ACLR limb/contralateral limb) were calculated for lateral and medial femoral condyle regions of interest. We conducted univariate linear regression analyses to determine associations between T1rho MRI ILRs and daily steps and MVPA with and without controlling for sex. Greater T1rho MRI ILR of the central lateral femoral condyle, indicative of less proteoglycan density in the ACLR limb, was associated with greater time in MVPA ( R2 = 0.178, P = 0.032). Sex-adjusted models showed significant interaction terms between daily steps and sex in the anterior ( P = 0.025), central ( P = 0.002), and posterior ( P = 0.002) medial femoral condyle. Lesser physical activity may be a risk factor for maintaining cartilage health after ACLR; additionally, the relationship between physical activity and cartilage health may be different between males and females.

Protective Effect of Low-Volume High-Intensity Interval Training on Aspirin-Induced Reproductive Impairments in Adult Male Wistar Rats.

Lifestyle factors such as sedentary behavior and consumption of certain medications can disturb the function of the male reproductive system. In the present study, we investigated the potential co-treatment effects of low-volume high-intensity interval training (HIIT) on markers of reproductive function in adult male Wistar rats under aspirin (ASA) treatment. Eighteen adult male Wistar rats were randomized into three groups: control (C), aspirin treatment (AT), and aspirin treatment + exercise (ATE). Animals in the AT and ATE groups received an oral subchronic dose of aspirin (12.5 mg/kg body mass). The exercise was performed three times per week for 6 weeks (4-6 reps of 10-s sprints). Serum testosterone level, sperm parameters (sperm count, viability, maturity, and DNA fragmentation), histomorphometric (Leydig cell, tubule diameter, thickness of tubular epithelium, and indices of spermatogenesis and spermiogenesis), and histochemical parameter (testicular fat density) were assessed. Results revealed that compared to the C group, ASA consumption led to a negative alteration in serum testosterone levels, sperm parameters, and histomorphometric and histochemical parameters (P < 0.05). However, there were no significant differences between the C and ATE groups in terms of serum testosterone level, number of Leydig cells, epididymal fat density, tubule diameter, epithelium height, immature-to-mature sperm ratio, and DNA breakage (P > 0.05). These findings suggest that ASA treatment is associated with deleterious changes in male reproductive parameters. However, low-volume HIIT may prevent ASA-induced male reproductive impairments and could be considered a potential prophylactic measure in subjects under ASA treatment.

Eutectic phase transition during tablet manufacture: effect of melting point of eutectic forming drug

The aim was to investigate eutectic transition during tableting and storage. Mixtures of lidocaine and series of NSAIDs with increasing melting point were used as model systems to guide formulators to scaleup eutectic forming materials gaining enhanced dissolution while avoiding deleterious physical changes. Physical mixtures of NSAIDs with lidocaine were prepared at eutectic forming ratio. These were directly compressed, dry co-ground before compression, or compressed after wet granulation. Dissolution of tablets was compared to corresponding dry co-ground mixture. Thermograms of direct compressed tablet were compared to co-ground mixture and pure compound. Stability of direct compressed tablets was assessed. Tableting initiated eutexia which enhanced dissolution of NSAIDs. Eutexia was associated with tablet softening in case of low melting point ketoprofen and aceclofenac. Wet granulation hastened eutexia developing unacceptable tablet in case ketoprofen and aceclofenac. Tablets prepared by direct compression of physical mixtures underwent gradual eutectic transition upon storage with the magnitude of eutectic transition reducing with increased melting point of NSAIDs. Ketoprofen was physically unstable but aceclofenac degraded chemically as well. Tenoxicam and meloxicam tablets were physically and chemically stable. Direct compression after physical mixing is the best tableting technique, but low melting point drugs should consider different strategy before compression.

Trained immunity in diabetes and hyperlipidemia: Emerging opportunities to target cardiovascular complications and design new therapies.

Some metabolic diseases, such as diabetes and hyperlipidemia, are associated with a state of inflammation, which adversely affects cardiovascular health. Emerging evidence suggests that long-term hyperactivation of innate immune cells and their bone marrow progenitors, termed trained immunity, functions to accelerate atherosclerosis and its complications in cardiometabolic diseases. This review will focus on how trained immunity is established, particularly through metabolic and epigenetic reprogramming, to cause persistent and deleterious changes in immune cell function, even after the original stimulus has been corrected or removed. Understanding the mechanisms driving maladaptive trained immunity and its fundamental contribution to cardiovascular disease might enable the development of novel disease-modifying therapeutics for the reduction in cardiovascular risk in diabetes, hyperlipidemia, and related cardiometabolic states.

Social defeat and psychosis-related outcomes: Associative and experimental tests related to the nature of defeat, specificity of outcomes, and psychosis-proneness

Several forms of social defeat, including ostracism, discrimination, bullying, and related experiences, have been associated with psychotic disorders and experiences. The social defeat hypothesis of schizophrenia attempts to explain these associations by positing that chronic exclusion due to having outsider status leads to deleterious neurobiological changes that produce psychosis. Here, we test non-neurobiological tenets of this theory, including the relative impact of daily, real-world, chronic social defeat versus an acute, time-limited, experimentally-induced socially defeating experience (social exclusion), the moderating role of psychosis-proneness, and the specificity of social defeat on psychosis-related outcomes. We find that real-world, chronic, but not acute, time-limited, laboratory-based social defeat is associated with decreased trust, but not false-alarms on an auditory signal detection task. These associations were qualified by interactions that are in line with social reconnection (i.e., positive appraisals of social stimuli following exclusion). Real-world, chronic social defeat was also associated with delusion- and hallucination-proneness. Together, these data highlight the importance of daily, real-world forms of social defeat versus laboratory manipulations on specific psychosis-related outcomes.

AQcalc: A web server that identifies weak molecular interactions in protein structures.

Weak molecular interactions play an important role in protein structure and function. Computational tools that identify weak molecular interactions are, therefore, valuable for the study of proteins. Here, we present AQcalc, a web server (https://aqcalcbiocomputing.com/) that can be used to identify anion-quadrupole (AQ) interactions, which are weak interactions involving aromatic residue (Trp, Tyr, and Phe) ring edges and anions (Asp, Glu, and phosphate ion) both within proteins and at their interfaces (protein-protein, protein-nucleic acids, and protein-lipid bilayer). AQcalc identifies AQ interactions as well as clusters involving AQ, cation-π, and salt bridges, among others. Utilizing AQcalc we analyzed weak interactions in protein models, even in the absence of experimental structures, to understand the contributions of weak interactions to deleterious structural changes, including those associated with oncogenic and germline disease variants. We identified several deleterious variants with disrupted AQ interactions (comparable in frequency to cation-π disruptions). Amyloid fibrils utilize AQ to bury anions at frequencies that far exceed those observed for globular proteins. AQ interactions were detected three and five times more frequently than the hydrogen-bonded AQ (HBAQ) in fibril structures and protein-lipid bilayer interfaces, respectively. By contrast, AQ and HBAQ interactions were detected with similar frequencies in globular proteins. Collectively, these findings suggest AQcalc will be effective in facilitating fine structural analysis. As other web utilities designed to identify protein residue interaction networks do not report AQ interactions, wide use of AQcalc will enrich our understanding of residue interaction networks and facilitate hypothesis testing by identifying and experimentally characterizing these comparably weak but important interactions.

Use of Saccharomyces boulardii CNCM I-745 as therapeutic strategy for prevention of nonsteroidal anti-inflammatory drug-induced intestinal injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. This study examined the protective effects of the probiotic Saccharomyces boulardii CNCM I-745 in a rat model of diclofenac-induced enteropathy. Enteropathy was induced in 40-week-old male rats by intragastric diclofenac (4 mg·kg-1 BID for 14 days). S.boulardii CNCM I-745 (3 g·kg-1 BID by oral gavage) was administered starting 14 days before (preventive protocol) or along with (curative protocol) diclofenac administration. Ileal damage, inflammation, barrier integrity, gut microbiota composition and toll-like receptors (TLRs)-nuclear factor κB (NF-κB) pathway were evaluated. Diclofenac elicited intestinal damage, along with increments of myeloperoxidase, malondialdehyde, tumour necrosis factor and interleukin-1β, overexpression of TLR2/4, myeloid differentiation primary response 88 (Myd88) and NF-κB p65, increased faecal calprotectin and butyrate levels, and decreased blood haemoglobin levels, occludin and butyrate transporter monocarboxylate transporter 1 (MCT1) expression. In addition, diclofenac provoked a shift of bacterial taxa in both faecal and ileal samples. Treatment with S.boulardii CNCM I-745, in both preventive and curative protocols, counteracted the majority of these deleterious changes. Only preventive administration of the probiotic counteracted NSAID-induced decreased expression of MCT1 and increase in faecal butyrate levels. Occludin expression, after probiotic treatment, did not significantly change. Treatment with S.boulardii CNCM I-745 prevents diclofenac-induced enteropathy through anti-inflammatory and antioxidant activities. Such effects are likely to be related to increased tissue butyrate bioavailability, through an improvement of butyrate uptake by the enteric mucosa.

Acoustomicrofluidic synthesis of ZIF-8/HRP metal–organic framework composites with enhanced enzymatic activity and stability

Encapsulating enzymes within metal–organic frameworks (MOFs) constitute a promising strategy to circumvent their fragile nature in harsh environments, although deleterious molecular conformational changes and decreased substrate accessibility within the pores of the MOF during enzyme loading can often result in decreased catalytic activity. Herein, we report a rapid (within seconds) and facile one-pot aerosol-based method for simultaneous MOF crystallisation and enzyme encapsulation for the synthesis of ZIF-8/horseradish peroxidase (HRP) biocomposites using a high frequency acoustomicrofluidic nebulisation platform. As a consequence of the enhanced mixing and fast crystallisation afforded by the acoustic coupling into the precursors, the resultant combination of enhanced porosity, missing-linker/metal-node defect creation, pore activation and favourable conformational changes to the enzyme secondary structure allows for more efficient enzyme loading and greater enzyme–substrate interactions, and hence stronger enzyme binding within the MOF structure. Together, these culminate in a biocomposite that possesses four times greater enzymatic activity compared to that for the same material synthesized using conventional bulk-solution techniques, and endows the enzyme with increased protective effect (by approximately three to seven times) against high temperature and organic solvents, even after several exposure cycles. Such a possibility facilitates better potential for the enzyme to be recycled—an important factor given their typically high costs and the difficulty in recovering free enzymes in solution.

Environmental enrichment through virtual reality as multisensory stimulation to mitigate the negative effects of prolonged bed rest.

Prolonged bed rest causes a multitude of deleterious physiological changes in the human body that require interventions even during immobilization to prevent or minimize these negative effects. In addition to other interventions such as physical and nutritional therapy, non-physical interventions such as cognitive training, motor imagery, and action observation have demonstrated efficacy in mitigating or improving not only cognitive but also motor outcomes in bedridden patients. Recent technological advances have opened new opportunities to implement such non-physical interventions in semi- or fully-immersive environments to enable the development of bed rest countermeasures. Extended Reality (XR), which covers augmented reality (AR), mixed reality (MR), and virtual reality (VR), can enhance the training process by further engaging the kinesthetic, visual, and auditory senses. XR-based enriched environments offer a promising research avenue to investigate the effects of multisensory stimulation on motor rehabilitation and to counteract dysfunctional brain mechanisms that occur during prolonged bed rest. This review discussed the use of enriched environment applications in bedridden patients as a promising tool to improve patient rehabilitation outcomes and suggested their integration into existing treatment protocols to improve patient care. Finally, the neurobiological mechanisms associated with the positive cognitive and motor effects of an enriched environment are highlighted.

Population transcriptogenomics highlights impaired metabolism and small population sizes in tree frogs living in the Chernobyl Exclusion Zone

BackgroundIndividual functional modifications shape the ability of wildlife populations to cope with anthropogenic environmental changes. But instead of adaptive response, human-altered environments can generate a succession of deleterious functional changes leading to the extinction of the population. To study how persistent anthropogenic changes impacted local species’ population status, we characterised population structure, genetic diversity and individual response of gene expression in the tree frog Hyla orientalis along a gradient of radioactive contamination around the Chernobyl nuclear power plant.ResultsWe detected lower effective population size in populations most exposed to ionizing radiation in the Chernobyl Exclusion Zone that is not compensated by migrations from surrounding areas. We also highlighted a decreased body condition of frogs living in the most contaminated area, a distinctive transcriptomics signature and stop-gained mutations in genes involved in energy metabolism. While the association with dose will remain correlational until further experiments, a body of evidence suggests the direct or indirect involvement of radiation exposure in these changes.ConclusionsDespite ongoing migration and lower total dose rates absorbed than at the time of the accident, our results demonstrate that Hyla orientalis specimens living in the Chernobyl Exclusion Zone are still undergoing deleterious changes, emphasizing the long-term impacts of the nuclear disaster.

Early clinical outcomes and molecular smooth muscle cell phenotyping using a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome

ObjectivesPatients with Loeys-Dietz syndrome demonstrate a heightened risk of distal thoracic aortic events after valve-sparing aortic root replacement. This study assesses the clinical risks and hemodynamic consequences of a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome and characterizes smooth muscle cell phenotype in Loeys-Dietz syndrome aneurysmal and normal-sized downstream aorta. MethodsPatients with genetically confirmed Loeys-Dietz syndrome (n = 8) underwent prophylactic aortic arch replacement during valve-sparing aortic root replacement. Four-dimensional flow magnetic resonance imaging studies were performed in 4 patients with Loeys-Dietz syndrome (valve-sparing aortic root replacement + arch) and compared with patients with contemporary Marfan syndrome (valve-sparing aortic root replacement only, n = 5) and control patients (without aortopathy, n = 5). Aortic tissues from 4 patients with Loeys-Dietz syndrome and 2 organ donors were processed for anatomically segmented single-cell RNA sequencing and histologic assessment. ResultsPatients with Loeys-Dietz syndrome valve-sparing aortic root replacement + arch had no deaths, major morbidity, or aortic events in a median of 2 years follow-up. Four-dimensional magnetic resonance imaging demonstrated altered flow parameters in patients with postoperative aortopathy relative to controls, but no clear deleterious changes due to arch replacement. Integrated analysis of aortic single-cell RNA sequencing data (>49,000 cells) identified a continuum of abnormal smooth muscle cell phenotypic modulation in Loeys-Dietz syndrome defined by reduced contractility and enriched extracellular matrix synthesis, adhesion receptors, and transforming growth factor-beta signaling. These modulated smooth muscle cells populated the Loeys-Dietz syndrome tunica media with gradually reduced density from the overtly aneurysmal root to the nondilated arch. ConclusionsPatients with Loeys-Dietz syndrome demonstrated excellent surgical outcomes without overt downstream flow or shear stress disturbances after concomitant valve-sparing aortic root replacement + arch operations. Abnormal smooth muscle cell–mediated aortic remodeling occurs within the normal diameter, clinically at-risk Loeys-Dietz syndrome arch segment. These initial clinical and pathophysiologic findings support concomitant arch replacement in Loeys-Dietz syndrome.

Cardioprotective efficacy of Xin-shu-bao tablet in heart failure with reduced ejection fraction by modulating THBD/ARRB1/FGF1/STIM1 signaling

Traditional Chinese medicine offer unique advantages in mitigating and preventing early or intermediate stage for treating heart failure (HF). The purpose of this study was to assess the in vivo therapeutic efficacy of Xin-shu-bao (XSB) at different stages of HF following induction of a myocardial infarction (MI) in mice and use mass spectrometry-based proteomics to identify potential therapeutic targets for different stages of HF based on the molecular changes following XSB treatment. XSB had high cardioprotective efficacy in the pre-HF with reduced ejection fraction (HFrEF) stages, but had a weak or no effect in the post-HFrEF stages. This was supported by echocardiographic measurements showing that XSB decreased ejection fraction and fractional shortening in HF. XSB administration improved cardiac function in the pre- and post-HFrEF mouse model, ameliorated deleterious changes to the morphology and subcellular structure of cardiomyocytes, and reduced cardiac fibrosis. Proteomics analysis showed that XSB intervention exclusively targeted thrombomodulin (THBD) and stromal interaction molecule 1 (STIM1) proteins when administered to the mice for both 8 and 6 weeks. Furthermore, XSB intervention for 8, 6, and 4 weeks after MI induction increased the expression of fibroblast growth factor 1 (FGF1) and decreased arrestin β1 (ARRB1), which are classic biomarkers of cardiac fibroblast transformation and collagen synthesis, respectively. Overall, the study suggests that early intervention with XSB could be an effective strategy for preventing HFrEF and highlights potential therapeutic targets for further investigation into HFrEF remediation strategies.

Novel insights into the role of mitochondria in diabetic cardiomyopathy: molecular mechanisms and potential treatments.

Diabetic cardiomyopathy describes decreased myocardial function in diabetic patients in the absence of other heart diseases such as myocardial ischemia and hypertension. Recent studies have defined numerous molecular interactions and signaling events that may account for deleterious changes in mitochondrial dynamics and functions influenced by hyperglycemic stress. A metabolic switch from glucose to fatty acid oxidation to fuel ATP synthesis, mitochondrial oxidative injury resulting from increased mitochondrial ROS production and decreased antioxidant capacity, enhanced mitochondrial fission and defective mitochondrial fusion, impaired mitophagy, and blunted mitochondrial biogenesis are major signatures of mitochondrial pathologies during diabetic cardiomyopathy. This review describes the molecular alterations underlying mitochondrial abnormalities associated with hyperglycemia and discusses their influence on cardiomyocyte viability and function. Based on basic research findings and clinical evidence, diabetic treatment standards and their impact on mitochondrial function, as well as mitochondria-targeted therapies of potential benefit for diabetic cardiomyopathy patients, are also summarized.