Search Results (58)

Background: Acute kidney injury (AKI), characterized by high morbidity and mortality, is primarily caused by renal ischemia–reperfusion injury (RIRI). Ferroptosis plays a key role in RIRI, yet its underlying mechanisms remain unclear. The drug pair of Astragali Radix–Ligustri Lucidi Fructus (DAL) shows promise in renal diseases, but its protective effects against RIRI and associated molecular pathways via ferroptosis inhibition are unknown. This study aimed to investigate DAL’s therapeutic effects on RIRI and its mechanisms. Methods: A mouse model of bilateral renal ischemia–reperfusion was established. Renal function (serum creatinine, Scr; blood urea nitrogen, BUN), inflammatory cytokines (TNF-α, IFN-γ, IL-6), ferroptosis markers (GPX4, MDA, GSH, tissue iron), and pathological damage were evaluated. Transcriptomic sequencing and electron microscopy analyzed gene pathways and mitochondrial structure. In HK-2 cells, oxygen–glucose deprivation/reoxygenation (OGD/R) and RSL3-induced ferroptosis models were used to assess DAL-containing serum effects via cell viability, GPX4 expression, and mitochondrial morphology. LC-MS analyzed DAL’s chemical components, and network pharmacology predicted ferroptosis-related targets. Results: DAL significantly reduced Scr/BUN levels, alleviated tubular injury, fibrosis, and apoptosis, and downregulated inflammatory cytokines and damage markers. It inhibited ferroptosis by upregulating GPX4, decreasing MDA/tissue iron, and increasing GSH. Transcriptomics revealed enrichment in lipid metabolism pathways. DAL restored the mitochondrial cristae structure; DAL-containing serum improved cell viability, blocked RSL3-induced GPX4 downregulation, and mitigated mitochondrial dysfunction. Network pharmacology identified DAL’s potential active components and targets. Molecular docking validated binding affinity and interaction patterns of active components with targets. Conclusions: DAL protects against RIRI by upregulating GPX4, preserving the mitochondrial structure, and inhibiting ferroptosis, highlighting its therapeutic potential for AKI prevention and treatment. Full article

It was previously reported that tyrosine 97 (Y97) of cytochrome c is phosphorylated in cow heart tissue under physiological conditions. Y97 phosphorylation was shown to partially inhibit respiration in vitro in the reaction with purified cytochrome c oxidase. Here, we use phosphomimetic Y97E Cytc to further characterize the functional effects of this modification both in vitro and in cell culture models. In vitro, phosphomimetic Y97E Cytc showed lower activity in the reaction with purified cow heart cytochrome c oxidase (COX), decreased caspase-3 activity, and reduced rate of reduction. Additionally, the phosphomimetic Y97E Cytc tended to be resistant to heme degradation and showed an increased rate of oxidation. Intact mouse Cytc double knockout fibroblasts were transfected with plasmids coding for phosphomimetic Y97E Cytc and other variants. Compared to cells expressing wild-type Cytc, the cells expressing phosphomimetic Y97E Cytc showed reduced respiration, mitochondrial membrane potential, and reactive oxygen species production, and protection from apoptosis. In an oxygen–glucose deprivation/reoxygenation cell culture model of ischemia/reperfusion injury, mitochondrial membrane potential and reactive oxygen species production were decreased. These data show that Cytc phosphorylation controls the overall flux through the electron transport chain by maintaining optimal intermediate ΔΨm potentials for efficient ATP production while minimizing reactive oxygen species production, thus protecting the cell from apoptosis. Full article

Background: Metabolic cancers are defined by metabolic reprogramming. Although this reprograming drives rapid tumour growth and invasion, it also reveals specific metabolic vulnerabilities that can be therapeutically exploited in cancer therapy. A novel form of programmed cell death, known as disulfidptosis, was identified last year; tumour cells with high SLC7A11 expression undergo disulfidptosis when deprived of glucose. Natural products have attracted increasing attention and have shown potential to treat metabolic cancers through diverse mechanisms. Methods: We systematically searched electronic databases involving PubMed, Web of Science, Gooale Scholar. To ensue comprehensive exploration, keywords including metabolic reprogramming, metabolic cancer, disulfidptosis, natural products and some other words were employed. Results: In this review, we focus on the shared characteristics and metabolic vulnerabilities of metabolic cancers. Additionally, we discuss the molecular mechanisms underlying disulfidptosis and highlight key regulatory genes. Furthermore, we predict bioactive natural products that target disulfidptosis-related genes, offering new perspectives for anticancer strategies through the modulation of disulfidptosis. Conclusions: By summarizing current research progress, this review mainly analyzed the potential mechanisms of natural products in the treatment of metabolic cancer. Full article

Background: Ethnic and socioeconomic disparities in cancer outcomes are exacerbated by clinical trial underrepresentation. This study aims to identify inequalities in ethnicity and socioeconomic features among ovarian cancer clinical trial participants in two London cancer centres. Methods: All ovarian cancer patients treated between 2017 and 2022 were included. Patients participating in clinical trials were classified as the trial population (TP); the remainder were considered the non-trial population (NTP). Data on disease characteristics and sociodemographic features, including ethnicity and Indices of Multiple Deprivation (IMD) deciles, were accessed from electronic patient records. Results: Of the 892 patients, 212 (24%) were enrolled in trials: 87 in Phase II, 103 in Phase III, and 21 in prospective, non-investigational medicinal product trials. The TP were more likely to be of White ethnicity (72.6% vs. 57.5%; p < 0.001), younger (mean age 58 vs. 60; p = 0.003), living in less deprived areas (most deprived tercile: 21.2% vs. 34.0%; p = 0.004), and English-speaking (95.8% vs. 90.9%; p = 0.041). In the multivariate analysis, White ethnicity (p < 0.0001), age (p = 0.003), IMD decile (p = 0.007), and interpreter requirement (p = 0.037) were independent predictors of trial participation. Conclusions: Ethnic and socioeconomic inequalities affect trial participation, potentially worsening health disparities in ovarian cancer patients. Strategies to overcome trial recruitment barriers for underserved groups are needed to improve the equity of care. Full article

Microbes frequently experience nutrient deprivations in the natural environment and may enter dormancy. Aggregatibacter actinomycetemcomitans is known to establish long-term infections in humans. This study examined the dormancy-like phenotype of an A. actinomycetemcomitans strain D7S-1 and its isogenic smooth-colony mutant D7SS. A tissue culture medium RPMI-1640 was nutrient-deficient (ND) and unable to support A. actinomycetemcomitans growth. RPMI-1640 amended with bases was nutrient-limited (NL) and supported limited growth of A. actinomycetemcomitans less than the nutrient-enriched (NE) laboratory medium did. Strain D7S-1, after an initial 2-log reduction in viability, maintained viability from day 4 to day 15 in the NL medium. Strain D7SS, after 1-log reduction in viability, maintained viability from day 3 to day 5. In contrast, bacteria in the NE medium were either non-recoverable (D7S-1; >6-log reduction) or continued to lose viability (D7SS; 3-log reduction) on day 5 and beyond. Scanning and transmission electron microscopy showed that A. actinomycetemcomitans in the NL medium formed robust biofilms similar to those in the NE medium but with evidence of stress. A. actinomycetemcomitans in the ND medium revealed scant biofilms and extensive cellular damage. We concluded that A. actinomycetemcomitans grown in the NL medium exhibited a dormancy-like phenotype characterized by minimum growth, prolonged viability, and distinct cellular morphology. Full article

The olive fruit fly, known as Bactrocera oleae (Rossi) (Diptera: Tephritidae), is causing substantial economic losses in olive crops worldwide. Studying the activity patterns of the insect may expand our knowledge to eventually adopt more sustainable and effective pest control approaches. In the present study, we investigated the impact of food and water deprivation on the mobility of olive fruit flies using a modified version of the LAM25 system (locomotor activity monitor)—Trikinetics, an automated locomotor activity electronic device. Both male and female flies at four different age groups, reared on olives in the laboratory, were individually placed in glass tubes. Their locomotor activity was recorded every minute by three monitors within the digital device over a three-day period. Our observations revealed that adults exhibited significantly reduced movement during nighttime compared to daytime. The greatest mobility was observed during the period of 15:00 to 20:59. Additionally, younger flies demonstrated higher levels of mobility compared to older ones. Flies subjected to both food and water deprivation exhibited higher mobility compared to the control group. These insights offer valuable insights for enhancing pest management strategies aimed at controlling olive fruit flies adopting a more sustainable approach. Full article

Global warming due to climate change has increased the frequency of sand and dust storms that affect air quality and ecosystems in general, contributing to air pollution. The Sahara Desert is the most potent emitter of atmospheric dust. The atmosphere is an extreme environment and microorganisms living in the troposphere are exposed to greater ultraviolet radiation, desiccation, low temperatures and nutrient deprivation than in other habitats. The Iberian Peninsula, and specifically the Canary Islands—due to its strategic location—is one of the regions that receive more Saharan dust particles annually, increasing year after year, although culturable microorganisms had previously never been described. In the present work, dust samples were collected from three calima events in the Canary Islands between 2021 and 2022. The sizes, mineralogical compositions and chemical compositions of dust particles were determined by laser diffraction, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), respectively. Particle morphology and biological features were also studied by scanning electron microscopy (SEM-EDX) and confocal laser scanning microscopy (CLSM). The mineral–bacteria interactions were described from microscopic observations, which revealed the presence of iberulites and small neoformed kaolinite crystals in association with bacteria. This article defines the term “mineral atmospherogenesis” and its variant, “mineral bioatmospherogenesis”, through microbial interaction. This is the first described case of kaolinite produced through mineral bioatmospherogenesis. The bacterial growth in atmospheric dust was illustrated in SEM images, constituting a novel finding. Twenty-three culturable microorganisms were isolated and identified by 16S rRNA sequencing. Members of the phyla Pseudomonadota, Bacillota and Actinomycetota have been found. Some of these microorganisms, such as Peribacillus frigoritolerans, have Plant Growth-Promoting Rhizobacteria (PGPR) properties. Potential human pathogenic bacteria such as Acinetobacter lwoffii were also found. The presence of desert dust and iberulites in the Canary Islands, together with transported biological components such as bacteria, could have a significant impact on the ecosystem and human health. Full article

The uncontrolled spread of drug-resistant tuberculosis (DR-TB) clinical cases necessitates the urgent discovery of newer chemotypes with novel mechanisms of action. Here, we report the chemical synthesis of rationally designed novel transition-state analogues (TSAs) by targeting the cyclization (Cy) domain of phenyloxazoline synthase (MbtB), a key enzyme of the conditionally essential siderophore biosynthesis pathway. Following bio-assay-guided evaluation of TSA analogues preferentially in iron-deprived and iron-rich media to understand target preferentiality against a panel of pathogenic and non-pathogenic mycobacteria strains, we identified a hit, i.e., TSA-5. Molecular docking, dynamics, and MMPBSA calculations enabled us to comprehend TSA-5’s stable binding at the active site pocket of MbtB_Cy and the results imply that the MbtB_Cy binding pocket has a strong affinity for electron-withdrawing functional groups and contributes to stable polar interactions between enzyme and ligand. Furthermore, enhanced intracellular killing efficacy (8 μg/mL) of TSA-5 against Mycobacterium aurum in infected macrophages is noted in comparison to moderate in vitro antimycobacterial efficacy (64 μg/mL) against M. aurum. TSA-5 also demonstrates whole-cell efflux pump inhibitory activity against Mycobacterium smegmatis. Identification of TSA-5 by focusing on the modular MbtB_Cy domain paves the way for accelerating novel anti-TB antibiotic discoveries. Full article

Photosystem I (PSI) is a critical component of the photosynthetic machinery in plants. Under conditions of environmental stress, PSI becomes photoinhibited, leading to a redox imbalance in the chloroplast. PSI photoinhibition is caused by an increase in electron pressure within PSI, which damages the iron–sulfur clusters. In this study, we investigated the susceptibility of PSI to photoinhibition in plants at different concentrations of CO₂, followed by global gene expression analyses of the differentially treated plants. PSI photoinhibition was induced using a specific illumination protocol that inhibited PSI with minimal effects on PSII. Unexpectedly, the varying CO₂ levels combined with the PSI-PI treatment neither increased nor decreased the likelihood of PSI photodamage. All PSI photoinhibition treatments, independent of CO₂ levels, upregulated genes generally involved in plant responses to excess iron and downregulated genes involved in iron deficiency. PSI photoinhibition also induced genes encoding photosynthetic proteins that act as electron acceptors from PSI. We propose that PSI photoinhibition causes a release of iron from damaged iron–sulfur clusters, which initiates a retrograde signal from the chloroplast to the nucleus to modify gene expression. In addition, the deprivation of CO₂ from the air initiated a signal that induced flavonoid biosynthesis genes, probably via jasmonate production. Full article

Cerebral ischemia, a leading cause of disability and mortality worldwide, triggers a cascade of molecular and cellular pathologies linked to several central nervous system (CNS) disorders. These disorders primarily encompass ischemic stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, and other CNS conditions. Despite substantial progress in understanding and treating the underlying pathological processes in various neurological diseases, there is still a notable absence of effective therapeutic approaches aimed specifically at mitigating the damage caused by these illnesses. Remarkably, ischemia causes severe damage to cells in ischemia-associated CNS diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including mitochondrial permeability transition pore (MPTP) opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species (ROS) and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of ischemia-associated CNS diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in cerebral ischemia have not yet been clarified. Thus, we analyzed the underlying mechanism between mitochondrial dysfunction and ferroptosis in ischemia-associated CNS diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of ROS and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of ischemia-associated CNS diseases. Full article

This literature review of growth hormone (GH) therapy and sleep-related health outcomes in children diagnosed with Prader–Willi syndrome (PWS) assembles evidence for the consequences of sleep deprivation and poor sleep quality: difficulty concentrating and learning at school, behavioral problems, diminished quality of life, and growth impairment. Sleep-disordered breathing (SDB) is another factor that impacts a child’s well-being. We searched the electronic databases Medline PubMed Advanced Search Builder, Scopus, and Web of Science using MeSH terms and text words to retrieve articles on GH deficiency, recombinant human growth hormone (rhGH) therapy, sleep quality, SDB, and PWS in children. The censor date was April 2023. The initial search yielded 351 articles, 23 of which were analyzed for this review. The study findings suggest that while GH may have a role in regulating sleep, the relationship between GH treatment and sleep in patients with PWS is complex and influenced by GH dosage, patient age, and type and severity of respiratory disorders, among other factors. GH therapy can improve lung function, linear growth, and body composition in children with PWS; however, it can also trigger or worsen obstructive sleep apnea or hypoventilation in some. Long-term GH therapy may contribute to adenotonsillar hypertrophy and exacerbate sleep apnea in children with PWS. Finally, GH therapy can improve sleep quality in some patients but it can also cause or worsen SDB in others, leading to diminished sleep quality and overall quality of life. The current evidence suggests that the initial risk of worsening SDB may improve with long-term therapy. In conclusion, rhGH is the standard for managing patients with PWS. Nonetheless, its impact on respiratory function during sleep needs to be thoroughly evaluated. Polysomnography is advisable to assess the need for adenotonsillectomy before initiating rhGH therapy. Close monitoring of sleep disorders in patients with PWS receiving GH therapy is essential to ensure effective and safe treatment. Full article

Ferroptosis is closely associated with the pathophysiology of myocardial ischemia. Hydroxysafflor yellow A (HSYA), the main active ingredient in the Chinese herbal medicine safflower, exerts significant protective effects against myocardial ischemia/reperfusion injury (MI/RI). The aim of this study was to investigate the protective effects of HSYA against MI/RI and identify the putative underlying mechanisms. An in vivo model of acute MI/RI was established in C57 mice. Subsequently, the effects of HSYA on myocardial tissue injury were evaluated by histology. Lipid peroxidation and myocardial injury marker contents in myocardial tissue and serum and iron contents in myocardial tissue were determined using biochemical assays. Mitochondrial damage was assessed using transmission electron microscopy. H9C2 cardiomyocytes were induced in vitro by oxygen–glucose deprivation/reoxygenation, and ferroptosis inducer erastin was administered to detect ferroptosis-related indicators, oxidative-stress-related indicators, and expressions of ferroptosis-related proteins and HIF-1α. In MI/RI model mice, HSYA reduced myocardial histopathological damage, ameliorated mitochondrial damage in myocardial cells, and decreased total cellular iron and ferrous ion contents in myocardial tissue. HSYA increased the protein levels of SLC7A11, HIF-1α, and GPX4 and mitigated erastin- or HIF-1α siRNA-induced damage in H9C2 cells. In summary, HSYA alleviated MI/RI by activating the HIF-1α/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis. Full article

Acute sleep deprivation can reduce the cognitive ability and change the emotional state in humans. However, little is known about how brain EEGs and facial expressions change during acute sleep deprivation (SD). Herein, we employed 34 healthy adult male subjects to undergo acute SD for 36 h, during which, their emotional states and brain EEG power were measured. The subjects were divided randomly into electronic stimulation and control groups. We performed TDCS on the left dorsolateral prefrontal cortex for 2 mA and 30 min in the TDCS group. These results indicated that the proportion of disgusted expressions in the electrical stimulation group was significantly less than the controls after 36 h post-acute SD, while the proportion of neutral expressions was increased post-restorative sleep. Furthermore, the electrical stimulation group presented a more significant impact on slow wave power (theta and delta) than the controls. These findings indicated that emotional changes occurred in the subjects after 36 h post-acute SD, while electrical stimulation could effectively regulate the cortical excitability and excitation inhibition balance after acute SD. Full article

Sleep is extremely important for the homeostasis of the organism. In recent years, various studies have been carried out to address factors related to sleep patterns and their influence on food choices, as well as on the onset of chronic noncommunicable diseases. The aim of this article is to provide a scientific literature review on the possible role of sleep patterns on eating behavior and the risk of noncommunicable diseases. A search was performed on Medline (PubMed interface) using several keywords (e.g., “Factors Influencing Sleep” OR “Sleep and Chronic Diseases”). Articles published between 2000 and the present date that relate sleep to cyclic metabolic processes and changes in eating behavior were selected. Changes in sleep patterns are increasingly detected today, and these modifications are mainly caused by work and lifestyle conditions as well as a growing dependence on electronic devices. Sleep deprivation and the resultant short sleep duration lead to an increased appetite via an increase in the hunger hormone (ghrelin) and a decrease in the satiety hormone (leptin). Nowadays, sleep is undervalued, and thus often impaired, with consequences for the performance of various body systems. Sleep deprivation alters physiological homeostasis and influences eating behavior as well as the onset of chronic diseases. Full article

Background: For many years, occupational physicians have debated whether there is a link between working the night shift and depression and other co-occurring mental health issues, with an emphasis on work-related, biological, individual, and environmental factors. We performed this systematic review and meta-analysis to estimate the overall association between sleep deprivation and depression among nurses working night shifts. Methods: A systematic search was carried out across the electronic databases PubMed, Scopus, and Web of Science from inception to 30 September 2022, for studies that reported a relationship between estimated night shift work and depression in nurses. The outcomes were measured using the odds ratio (OR) and matching 95% confidence interval (CI). The I² statistic was used to assess heterogeneity. The Grading of Recommendations Assessment, Development and Evaluation technique was used to evaluate the quality of the evidence, and the Newcastle–Ottawa Scale was utilized to assess the methodological quality of each of the included studies. We determined the overall relationship between working nights and the onset of depression. Results: A total of 20 studies were included in the systematic review. Furthermore, 8 studies were included in the meta-analysis due to their common use of the OR as an effect measure. The 8 studies gave an overall estimate indicating a statistically significant association between night shift work and depression among nurses (OR = 1.49 95% CI: 1.26, 1.76). The prediction interval for the overall estimate was (0.995, 2.231). This implies that the true OR in a future study would most likely fall within this range, with a 95% certainty. Conclusions: The outcome of this systematic review and meta-analysis showed a significant association between night shift work, the circadian and sleep disruption it causes, and the risk of depression in nurses. This demonstrates that nurses who work night shifts are at risk of developing depression. Full article