Protective Role Research Articles

Siderophores promote cooperative interspecies and intraspecies cross-protection against antibiotics in vitro.

The antibiotic cefiderocol hijacks iron transporters to facilitate its uptake and resists β-lactamase degradation. While effective, resistance has been detected clinically with unknown mechanisms. Here, using experimental evolution, we identified cefiderocol resistance mutations in Pseudomonas aeruginosa. Resistance was multifactorial in host-mimicking growth media, led to multidrug resistance and paid fitness costs in cefiderocol-free environments. However, kin selection drove some resistant populations to cross-protect susceptible individuals from killing by increasing pyoverdine secretion via a two-component sensor mutation. While pyochelin sensitized P. aeruginosa to cefiderocol killing, pyoverdine and the enterobacteria siderophore enterobactin displaced iron from cefiderocol, preventing uptake by susceptible cells. Among 113 P. aeruginosa intensive care unit clinical isolates, pyoverdine production directly correlated with cefiderocol tolerance, and high pyoverdine producing isolates cross-protected susceptible P. aeruginosa and other Gram-negative bacteria. These in vitro data show that antibiotic cross-protection can occur via degradation-independent mechanisms and siderophores can serve unexpected protective cooperative roles in polymicrobial communities.

Happy Moments between Children and Their Parents: A Multi-method and Multi-informant Perspective

Research interest in children’s happiness has increasingly grown in recent years. Studies of children’s happiness have shown that happiness promotes greater social and emotional well-being during childhood. The present study explores the different perspectives of children and their parents on happy moments spent together, examining potential discrepancies in points of view. Semi-structured interviews were conducted with 154 children (6–13 years old: Mage=8.72, SD = 2.00; 57% girls), their mothers (Mage=42.30, SD = 4.50), and their fathers (Mage=45.47, SD = 5.42). Children were asked to indicate their level of happiness using a single item and to recount their happy moments spent with their fathers and mothers. Parents were asked to evaluate their children’s happiness and to identify what they thought was the happiest moment their children had experienced with them. The data was analyzed using Thematic Analysis. Six main themes related to children’s happy moments emerged from the transcripts: (1) Activities outside the home; (2) Shared activities between parents and children; (3) Happy moments of play between parents and children; (4) Parent-child moments of affection; (5) Relevance of material gifts; (6) Non-specified happy moments. Emotional interactions characterized the happiest moments reported with mothers, while those with fathers were more frequently playful and fun situations. Results showed that parents and children disagree on children’s happiness levels and tend to identify different episodes as the happiest moments spent together. The study examined parent-child interactions in the context of family happiness, considering the protective role of a child’s happiness against negative psychological symptoms. It aimed to identify components of happier moments as potential indicators of family well-being, given the family’s role in psychological development.

The protective role of ginsenoside Rg3 in heart diseases and mental disorders.

Ginsenoside Rg3, a compound derived from Panax ginseng C. A. Mey., is increasingly recognized for its wide range of pharmacological effects. Under the worldwide healthcare challenges posed by heart diseases, Rg3 stands out as a key subject in modern research on Chinese herbal medicine, offering a novel approach to therapy. Mental illnesses are significant contributors to global disease mortality, and there is a well-established correlation between cardiac and psychiatric conditions. This connection is primarily due to dysfunctions in the sympathetic-adrenomedullary system (SAM), the hypothalamic-pituitary-adrenal axis, inflammation, oxidative stress, and brain-derived neurotrophic factor impairment. This review provides an in-depth analysis of Rg3's therapeutic benefits and its pharmacological actions in treating cardiac and mental health disorders respectively. Highlighting its potential for the management of these conditions, Rg3 emerges as a promising, multifunctional therapeutic agent.

Serum fetuin-a and risk of thoracic aortic aneurysms: a two-sample mendelian randomization study.

Recent studies have revealed a significant decrease in serum fetuin-A levels in atherosclerotic aneurysms, indicating that fetuin-A may play a protective role in the progression of arterial calcification. However, the specific mechanism behind this phenomenon remains unclear. We aimed to examine the association between fetuin-A levels in thoracic aortic aneurysms (TAAs) and risk of TAAs and to evaluate whether this association was causal. A total of 26 SNPs were selected as instrumental variables for fetuin-A in 9,055 participants of European ancestry from the CHARGE consortium, and their effects on thoracic aortic aneurysm and decreased descending thoracic aortic diameter were separately estimated in 353,049 and 39,688 individuals from FinnGen consortium. We used two-sample Mendelian randomization (MR) analysis to examine the causal association. At the same time, we employed various methods, including random-effects inverse variance weighting, weighted median, MR Egger regression, and MR PRESSO, to ensure the robustness of causal effects. We assessed heterogeneity using Cochran's Q value and examined horizontal pleiotropy through MR Egger regression and retention analysis. Fetuin-A level was associated with a significantly decreasing risk of thoracic aortic aneurysm (odds ratio (OR) 0.64, 95% CI 0.47 - 0.87, P = 0.0044). Genetically predicted fetuin-A was also correlated with the decreased descending thoracic aortic diameter (β = -0.086, standard error (SE) 0.036, P = 0.017). Serum fetuin-A level was negatively associated with risk of TTAs and correlated with the decreased descending thoracic aortic diameter. Mendelian randomization provides support for the potential causal relationship between fetuin-A and thoracic aortic aneurysm.

Vitamin D supply, respiratory viral infections and persistent wheezing in children: how significant is the relationship?

The review discusses the multifaceted effect of vitamin D on antiviral immunity, induction of antimicrobial peptides, functional activity of immunocompetent cells, autophagy processes, clearance of viruses and viral fragments. The relationship between vitamin D and allergic inflammatory cells, its modulating and tolerogenic potential is considered. The inhibitory effect of vitamin D on eosinophils, mast cells, the production of pro-inflammatory and proallergic mediators, and the synthesis of IgE has been shown. The protective role of vitamin D in the development of remodeling and hyperresponsiveness of the respiratory tract has been established by reducing the number of goblet cells, mucus hypersecretion, and the expression of metalloproteinases. The effects of vitamin D on the replication of respiratory viruses and experimental resistance to them through the induction of antimicrobial peptides and other mechanisms have been demonstrated. Data from clinical studies on the preventive effect of vitamin D on the incidence of respiratory infections and episodes of persistent wheezing in children are presented. Children with respiratory syncytial infection and vitamin D deficiency were more likely to require respiratory support and mechanical ventilation. The preventive role of vitamin D in the development of obstructive bronchitis in children and severe bronchiolitis in infants has been shown. It has been established that normal levels of 25(OH)D in the mother significantly reduce the risk of developing bronchial obstruction in the child. Alternative data that do not support a protective effect of vitamin D on respiratory morbidity and wheezing in children are discussed. Further monitoring studies that take into account geographic location and analysis of the dose of cholecalciferol used to assess its preventive role in the development of wheezing and bronchial asthma in children are advisable.

Beliefs, practices and support needs of preschool teachers toward shy‐withdrawn behaviours

AbstractShy‐withdrawn behaviours place preschoolers at increased risk of experiencing adverse developmental outcomes. Positive teacher‐child relationships play a protective role against these negative socioemotional outcomes. This study aimed to understand, in‐depth, the beliefs, practices and support needs of preschool teachers toward shy‐withdrawn children. Thirty preschool teachers of children aged 3–5 years were interviewed, using a semistructured guide. The thematic analysis revealed that most preschool teachers were aware of the main manifestations, transactional influences and consequences of shy‐withdrawn behaviours, and of the empirically validated strategies that may be useful to modify them. However, a noteworthy proportion of participants reported misconceptions about the intentionality of shy‐withdrawn behaviours, negative emotions and inconsistent or less effective practices. Our findings highlight that strengthening pre‐service and in‐service training and providing coaching to the preschool staff may be helpful to restructure dysfunctional beliefs about shy‐withdrawn behaviours, translate developmental knowledge in evidence‐based classroom practices and enhance professionals' self‐awareness.Highlights This study explored, in‐depth, the beliefs, practices and support needs of preschool teachers toward shy‐withdrawn children. Most of the 30 interviewed preschool teachers were aware of the main manifestations, transactional influences and consequences of shy‐withdrawn behaviours. Our findings highlight the need to strengthen teachers' training, bridging theoretical knowledge with professional development.

Use of the traditional Chinese medicine “compound healthy ear agent” to protect against age-related hearing loss in mice: A proteomics study

BackgroundPrevious studies have shown that the traditional Chinese medicine (TCM) called “compound healthy ear agent” (CHEA) had anti-apoptosis effects in cochlear hair cells and spiral ganglion neurons, and could protect mice hearing against presbycusis or age-related hearing loss (AHL), as well as aminoglycoside antibiotic-induced ototoxicity. Because its mechanisms of action are still unclear, we investigated the mechanism of action of CHEA against AHL in mice using proteomics techniques. MethodsEighteen C57BL/6J mice at 1 month of age were randomly divided into three groups: (A) drinking water until 2 months of age, K2M); (B) drinking water until 7 months of age to induce AHL, K7M; (C) drinking water containing CHEA daily until 7 months of age as treatment group, Z7M. At 2 or 7 months mice were sacrificed and their cochleae were removed for proteomics analysis. ResultsThe numbers of proteins with a false discovery rate (FDR) < 1% were respectively 5873 for qualitative and 5492 for quantitative statistics. The numbers of proteins with differential enrichment at least 1.5-fold (p < 0.05) were respectively 351 for K7M vs K2M groups, 52 for Z7M vs K7M groups, 264 for Z7M vs K2M groups. The differentially expressed proteins in the Z7M group were involved in synaptic molecular transmission, energy metabolism, immune response, antioxidant defenses, and anti-apoptosis. ConclusionThe TCM CHEA played a protective role against AHL in mice by regulating the expression of specific proteins and genes in cochlear hair cells and spiral ganglion neurons. Besides the pathways expected to be involved (antioxidant and anti-apoptosis), proteins related to immune response is a new finding of the present study.

Urolithin B protects PC12 cells against glutamate-induced toxicity.

The involvement of malfunctioning glutamate systems in various central nervous system (CNS) disorders is widely acknowledged. Urolithin B, known for its neuroprotective and antioxidant properties, has shown potential as a therapeutic agent for these disorders. However, little is known about its protective effects against glutamate-induced toxicity in PC12 cells. Therefore, in this study, for the first time we aimed to investigate the ability of Urolithin B to reduce the cytotoxic effects of glutamate on PC12 cells. Different non-toxic concentrations of urolithin B were applied to PC12 cells for 24h before exposure to glutamate (10mM). The cells were then analyzed for cell viability, intracellular reactive oxygen species (ROS), cell cycle arrest, apoptosis, and the expression of Bax and Bcl-2 genes. The results of MTT assay showed that glutamate at a concentration of 10mM and urolithin B at a concentration of 114μM can reduce PC12 cell viability by 50%. However, urolithin B at non-toxic concentrations of 4 and 8μM significantly reduced glutamate-induced cytotoxicity (p < 0.01). Interestingly, treatment with glutamate significantly enhanced the intracellular ROS levels and apoptosis rate in PC12 cells, while pre-treatment with non-toxic concentrations of urolithin B significantly reduced these cytotoxic effects. The results also showed that pre-treatment with urolithin B can decrease the Bax (p < 0.05) and increase the Bcl-2 (p < 0.01) gene expression, which was dysregulated by glutamate. Taken together, urolithin B may play a protective role through reducing oxidative stress and apoptosis against glutamate-induced toxicity in PC12 cells, which merits further investigations.

Caffeic acid protects against l-methionine induced reduction in neurogenesis and cognitive impairment in a rat model

l-methionine (L-met) is a substantial non-polar amino acid for normal development. L-met is converted to homocysteine that leads to hyperhomocysteinemia and subsequent excessive homocysteine in serum resulting in stimulating oxidative stress and vascular dementia. Several studies have found that hyperhomocysteine causes neuronal cell damage, which leads to memory impairment. Caffeic acid is a substrate in phenolic compound discovered in plant biosynthesis. Caffeic acid contains biological antioxidant and neuroprotective properties. The neuroprotective reaction of caffeic acid can protect against the brain disruption from hydrogen peroxide produced by oxidative stress. It also enhances GSH and superoxide dismutase activities, which protect against neuron cell loss caused by oxidative stress in the hippocampus. Hence, we investigated the protective role of caffeic acid in hippocampal neurogenesis and cognitive impairment induced by L-met in rats. Six groups of Sprague Dawley rats were assigned including control, L-met (1.7 g/kg/day), caffeic acid (20, 40 mg/kg), and L-met + caffeic acid (20, 40 mg/kg) groups. Spatial and recognition memories were subsequently examined using novel object location (NOL) and novel object recognition (NOR) tests. Moreover, the immunofluorescence technique was performed to detect Ki-67/RECA-1, bromodeoxyuridine (BrdU)/NeuN and p21 markers to represent hippocampal neurogenesis changes. The results revealed decreases in vasculature related cell proliferation and neuronal cell survival. By contrast, cell cycle arrest was increased in the L-met group. These results showed the association of the spatial and recognition memory impairments. However, the deterioration can be restored by co-administration with caffeic acid.

Pterostilbene protects against H2 O2 -induced oxidative stress by regulating GAS6/Axl signaling in HL-1 cells.

Pterostilbene (PTE,trans-3,5-dimethoxy-4'-hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axlsignaling pathway in cardiomyocytes. Hydrogen peroxide (H2 O2 )-induced oxidative stress HL-1cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real-time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE'sprotective role. The results showed that PTEtreatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H2 O2 -injured HL-1cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE-mediated pleiotropic effects.

The role of frailty in the relationships between social relationships and health outcomes: a longitudinal study

BackgroundSocially isolated older adults incur increased risks of adverse health outcomes, though the strength of this association is unclear. We examined whether changes in physical frailty moderated the associations between changes in social relationships and changes in health outcomes among older adults.MethodsThis longitudinal study is based on three waves of the FRéLE study among 1643 Canadian community-dwelling older adults aged 65 years and older over 2 years. We performed latent growth curve modelling (LGMs) to assess changes with the assumption of missing not at random, adjusting for time-invariant covariates. We used the latent moderated structural equations (LMS) to test the interactions in LGMs. Social relationships were measured by social participation, social networks, and social support from different social ties. Frailty was assessed using the five components of the phenotype of frailty.ResultsThe results revealed that changes in frailty moderated changes in social participation (β = 3.229, 95% CI: 2.212, 4.245), social contact with friends (β = 4.980, 95% CI: 3.285, 6.675), and social support from friends (β = 2.406, 95% CI: 1.894, 2.917), children (β = 2.957, 95% CI: 1.932, 3.982), partner (β = 4.170, 95% CI: 3.036, 5.305) and extended family (β = 6.619, 95% CI: 2.309, 10.923) with changes in cognitive function and depressive symptoms, but not with chronic diseases. These results highlight the beneficial role of social relationships in declining depressive symptoms and improving cognitive health among older adults experiencing increases in frailty.ConclusionsThe findings suggest that changes in social support have a protective and compensatory role in decreasing depressive symptoms and enhancing cognitive health among older adults with increasing frailty. Public health policy and strategies should consider the impact of social support on multiple health outcomes among older adults with increasing frailty. Further experimental studies and interventions are warranted to extend findings on the relationships between social relationships and health outcomes, targeting frail older adults. Future studies may also consider other health-related risk factors that may impact the associations between social relationships and health outcomes among older adults.

The maternal embrace: the protection of plant embryos.

All land plants - the embryophytes - produce multicellular embryos, as other multicellular organisms, such as brown algae and animals. A unique characteristic of plant embryos is their immobile and confined nature. Their embedding in maternal tissues may offer protection from the environment, but also physically constrains development. Across the different land plants, a huge discrepancy is present between their reproductive structures whilst leading to similarly complex embryos. Therefore, we review the roles that maternal tissues play in the control of embryogenesis across land plants. These nurturing, constraining, and protective roles include both direct and indirect effects. In this review, we explore how the maternal surroundings affect embryogenesis and which chemical and mechanical barriers are in place. We regard these questions through the lens of evolution, and identify key questions for future research.

Curcumin attenuates aflatoxin B1-induced ileum injury in ducks by inhibiting NLRP3 inflammasome and regulating TLR4/NF-κB signaling pathway.

Aflatoxin B1 (AFB1) is a widespread toxic contamination in feed for animals. The primary active component of turmeric, curcumin (Cur), is an antioxidant and an anti-inflammatory. However, it is yet unknown how AFB1 affects the intestinal epithelial barrier and whether Cur acts as a protective mechanism when exposed to AFB1. Here, we explored the mechanism of AFB1-induced intestinal injury from intestinal epithelial barrier, inflammation, pyroptosis, and intestinal flora, and evaluated the protective role of Cur. We found that AFB1 caused weight loss and intestinal morphological damage that is mainly characterized by shortened intestinal villi, deepened crypts, and damaged intestinal epithelium. Exposure to AFB1 decreased the expression of Claudin-1, MUC2, ZO-1, and Occludin and increased the expression of pyroptosis-related factors (NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18) and inflammation-related factors (TLR4, NF-κB, IκB, IFN-γ, and TNF-α). Furthermore, ileal gut microbiota was altered, and simultaneously, the Lactobacillus abundance was decreased. The gut microbiota interacts with a wide range of physiologic functions and disease development in the host through its metabolites, and disturbances in gut microbial metabolism can cause functional impairment of the ileum. Meanwhile, Cur can ameliorate histological ileum injuries and intestinal flora disturbance caused by AFB1. We found that Cur reversed the effects of AFB1 through modulating both NLRP3 inflammasome and the TLR4/NF-κB signaling pathway. In conclusion, AFB1 can induce inflammatory damage and pyroptosis in duck ileum, while Cur has obviously protective effects on all the above damages.

Inhibiting apoptosis and GSDME-mediated pyroptosis attenuates hepatic injury in septic mice

BackgroundSepsis is characterized by severe inflammation and organ dysfunction resulting from a dysregulated organismal response to infection. Although pyroptosis has been presumably shown to be a major cause of multiple organ failure and septic death, whether gasdermin E (GSDME)-mediated pyroptosis occurs in septic liver injury and whether inhibiting apoptosis and GSDME-mediated pyroptosis can attenuate septic liver injury remain unclear. This study investigated the role of apoptosis and GSDME-mediated pyroptosis in septic liver injury. MethodsAdult male C57BL/6 mice were randomly divided into four groups: sham, cecal ligation puncture (CLP), CLP + Z-DEVD-FMK (a caspase-3 inhibitor, 5 mg/kg), and CLP + Ac-DMLD-CMK (a GSDME inhibitor, 5 mg/kg). Sepsis severity was assessed using the murine sepsis score (MSS). Hepatic tissue damage was observed by the hematoxylin-eosin staining method, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the levels of malondialdehyde (MDA), the concentrations of interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured according to the related kits, and the changes in the hepatic tissue reactive oxygen species (ROS) levels were detected by immunofluorescence (IF). The protein expression levels of cleaved caspase-3, GSDME-N, IL-1β, B-cell lymphoma-2 (Bcl-2), cytochrome C (Cyt-c), and acetaldehyde dehydrogenase 2 (ALDH2) were detected using western blotting. GSDME expression was detected by immunohistochemistry. ResultsCompared with the Sham group, CLP mice showed high sepsis scores and obvious liver damage. However, in the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups, the sepsis scores were reduced and liver injury was alleviated. Compared with the Sham group, the serum ALT and AST activities, MDA and ROS levels, and IL-1β and TNF-α concentrations were increased in the CLP group, as well as the protein expression of cleaved caspase-3, GSDME-N, IL-1β, Cyt-c, and GSDME positive cells (P < 0.05). However, the expression levels of Bcl-2 and ALDH2 protein were decreased (P < 0.05). Compared with the CLP group, the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups showed low sepsis scores, ALT and AST activities, MDA and ROS levels, decreased IL-1β and TNF-α concentrations, and decreased expression of cleaved caspase-3, GSDME-N, IL-1β protein expression, and GSDME positive cells (P < 0.05). The expression levels of Bcl-2 and ALDH2 protein were increased (P < 0.05). ConclusionApoptosis and GSDME-mediated pyroptosis are involved in the development of sepsis-induced hepatic injury. Inhibition of apoptosis and GSDME-mediated pyroptosis attenuates injury. ALDH2 plays a protective role by inhibiting apoptosis and pyroptosis.

The interplay of mitophagy, autophagy, and apoptosis in cisplatin-induced kidney injury: involvement of ERK signaling pathway

AKI induced by CP chemotherapy remains an obstacle during patient treatments. Extracellular signal-regulated protein kinases 1/2 (ERK), key participants in CP-induced nephrotoxicity, are suggested to be involved in the regulation of mitophagy, autophagy, and apoptosis. Human renal proximal tubular cells (HK-2) and BALB/cN mice were used to determine the role of ERK in CP-induced AKI. We found that active ERK is involved in cell viability reduction during apoptotic events but exerts a protective role in the early stages of treatment. Activation of ERK acts as a maintainer of the mitochondrial population and is implicated in mitophagy initiation but has no significant role in its conduction. In the late stages of CP treatment when ATP is deprived, general autophagy that requires ERK activation is initiated as a response, in addition to apoptosis activation. Furthermore, activation of ERK is responsible for the decrease in reserve respiratory capacity and controls glycolysis regulation during CP treatment. Additionally, we found that ERK activation is also required for the induction of NOXA gene and protein expression as well as FoxO3a nuclear translocation, but not for the regular ERK-induced phosphorylation of FoxO3a on Ser294. In summary, this study gives detailed insight into the involvement of ERK activation and its impact on key cellular processes at different time points during CP-induced kidney injury. Inhibitors of ERK activation, including Mirdametinib, are important in the development of new therapeutic strategies for the treatment of AKI in patients receiving CP chemotherapy.

Comparison of the Effect of Eight Weeks Aerobic and Combined Exercise on Some Hemodynamic Indicators in Middle-Aged Male Patients Undergoing Coronary Artery Bypass Graft Surgery

Introduction: Exercise training by modulating blood pressure and heart rate have a protective role for middle-aged cardiac patients. Aim of this study was to compare the effect of eight weeks of aerobic and combined exercise on some hemodynamic indicators in middle-aged male patients undergoing coronary artery bypass graft surgery.&#x0D; Methods: In this clinical trial, a sample of 30 middle-aged men who underwent coronary artery surgery in 2023 were enrolled after meeting predetermined eligibility criteria and randomized for participation. They were divided into three aerobic (n=10), combined (n=10) and control (n=10) groups. The individuals of the 2 intervention groups performed selected aerobic and combined exercises (with an intensity of 55 - 75% of the maximum heart rate, for 60 minutes) for 8 weeks, 3 sessions per week. Blood pressure, heart rate and peripheral oxygen saturation (SpO2) were measured before and after the intervention. The parametric paired sample t-test, one-way ANOVA test and Tukey's Test were used to examine differences at a significance level of P ≤ 0.05.&#x0D; Results: The effect of aerobic exercises on systolic blood pressure (P=0.036), diastolic blood pressure (P=0.040) and heart rate (P=0.013) was significant and caused a decrease in these indicators, but the decrease in the combined group was not significant (P&gt;0.05). The intergroup effect difference was not significant (P&gt;0.05). In both aerobic (P=0.000) and combined (P=0.007) groups, the peripheral oxygen saturation has increased significantly and intergroup mean difference was significant (P=0.004).&#x0D; Conclusion: It seems that aerobic and combined exercises as a helpful intervention strategy to improve hemodynamic indicators, make the patient more adaptable to the conditions after coronary artery bypass graft surgery.

Therapeutic potency of A1 adenosine receptor antagonists in the treatment of cardiovascular diseases, current status and perspectives.

Cardiomyocytes form, transport, and metabolize the omnipresent metabolite adenosine. Depending upon the adenosine concentrations and the pharmacological properties of receptor subtypes, adenosine exerts (patho)physiological responses in the cardiovascular system. The objective of this review is to present different protective mechanisms of A1-adenosine receptor inhibitors in cardiovascular diseases. Literature references were collected and sorted using relevant keywords and key phrases as search terms in scientific databases such as Web of Science, PubMed and Google Scholar. A1 adenosine receptor regulates free fatty acid metabolism, lipolysis, heart rate, blood pressure, and cardiovascular toxicity. The evidence clearly supporting the therapeutic potency of pharmacological A1 adenosine receptors agonists and antagonists in modulating cardiovascular risk factor parameters and treatment of cardiovascular diseases. This review summarizes the protective role of pharmacological A1-adenosine receptor regulators in the pathogenesis of cardiovascular diseases for a better management of cardiovascular diseases.

3-O-Methyl-D-Glucose Blunts Cold Ischemia Damage in Kidney via Inhibiting Ferroptosis

BackgroundThe glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. MethodsPretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. ResultsOMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells. ConclusionOur study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.

Thylakoid membrane stacking controls electron transport mode during the dark-to-light transition by adjusting the distances between PSI and PSII.

The balance between linear electron transport (LET) and cyclic electron transport (CET) plays an essential role in plant adaptation and protection against photo-induced damage. This balance is largely maintained by phosphorylation-driven alterations in the PSII-LHCII assembly and thylakoid membrane stacking. During the dark-to-light transition, plants shift this balance from CET, which prevails to prevent overreduction of the electron transport chain and consequent photo-induced damage, towards LET, which enables efficient CO2 assimilation and biomass production. Using freeze-fracture cryo-scanning electron microscopy and transmission electron microscopy of Arabidopsis leaves, we reveal unique membrane regions possessing characteristics of both stacked and unstacked regions of the thylakoid network that form during this transition. A notable consequence of the morphological attributes of these regions, which we refer to as 'stacked thylakoid doublets', is an overall increase in the proximity and connectivity of the two photosystems (PSI and PSII) that drive LET. This, in turn, reduces diffusion distances and barriers for the mobile carriers that transfer electrons between the two PSs, thereby maximizing LET and optimizing the plant's ability to utilize light energy. The mechanics described here for the shift between CET and LET during the dark-to-light transition are probably also used during chromatic adaptation mediated by state transitions.

Assessing future land-uses under planning scenarios: A case study of The Brantas River Basin, Indonesia

Understanding land-use dynamics and patterns and how they respond to management scenarios helps to develop sustainable land use policies. This study simulated future land uses in Brantas River Basin (BRB), East Java, Indonesia using Land Change Modeler (LCM) under policy scenarios. Following identification of twelve important biophysical and socio-economic spatial drivers, the LCM accurately simulated land-use changes over the period 1995–2015, with validation against the 1995 land use map giving an overall accuracy of 85–88 %. Under a business-as-usual scenario, the LCM predicted that during the period 2015 to 2035 continuing deforestation may leave forest cover accounting for only 4 % of the total BRB area, and cause declines in dryland from 45 % to 40 % and in rice-field farming from 24 % to 22 %. The results of that scenario also indicate the prospect of massive urban development, increasing from 18 % of the BRB area in 2015 to 30 % in 2035, with increasing threats to food security and water resources. Both percentage changes and a mean-weighted fractal dimension index suggest increased risks of forest fragmentation and urban aggregation. A spatial planning-influenced scenario, which aims to reduce forest loss and support watershed protection, is predicted to lead to 5.5 % forest cover, 37 % dryland, 29 % rice-field farming and 24 % urban area in 2035. Sensitivity analysis of the LCM showed that the model results were more sensitive to drivers, spatial resolution, and policy scenarios than to uncertainty in model parameters. It is concluded that despite some limitations, the LCM successfully provided" insights into policy impacts on land-uses in BRB, and the roles of forest and rice-field protection in spatial planning are essential in controlling urban development for watershed sustainability.