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American Journal of Cardiovascular... Jun 2024The clinical advantage of alprostadil [prostaglandin E1 (PGE1)] in the treatment of microcirculatory disturbances (defined as no-reflow or slow-flow) in acute...
OBJECTIVE
The clinical advantage of alprostadil [prostaglandin E1 (PGE1)] in the treatment of microcirculatory disturbances (defined as no-reflow or slow-flow) in acute percutaneous coronary intervention (PCI) is still disputed. The purpose of our study was to review the efficacy of PGE1 supplements in patients with acute myocardial infarction (AMI) who had urgent PCI.
DESIGN
This study was a meta-analysis of randomized controlled trials.
DATA SOURCES
PubMed, Embase, the Cochrane Library, Ovid, ProQuest, Scopus, the Chinese BioMedical Literature Database, China National Knowledge Internet, the China Science and Technology Journal Database, and the Wanfang Data Knowledge Service Platform were used as sources.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
We included randomized controlled trials including PGE1 for the treatment of intraoperative microcirculatory disorders and major cardiovascular adverse events in emergency PCI in people with AMI. Independent data extraction was conducted, and study quality was assessed. The meta-analysis was carried out by using random effects models to calculate the risk ratio (RR) of microcirculatory disorders between groups receiving PGE1 and those receiving placebo, nitroglycerin, or tirofiban.
MAIN OUTCOME MEASURES
The primary endpoint of the study was the incidence of microcirculatory disturbances. Secondary outcomes included corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), the percentage of patients with TIMI myocardial perfusion grade 3 (TMPG3), and the percentage of patients with myocardial blush grade 3 (MBG3) as efficacy indicators. Additionally, major adverse cardiovascular events (MACE) at 30 days and 180 days were assessed as safety indicators.
RESULTS
There were 18 trials involving a total of 1458 participants. PGE1 significantly reduced the occurrence of microcirculation disorders compared with conventional medications and placebo [risk ratio 0.48, 95% confidence interval (CI) 0.36-0.63, I = 46%; cTFC (RR -4.74, 95% -6.85 to -2.63, I 93%); percentage of patients with TMPG3 (RR 1.34, 95% CI 1.07-1.68, I 70%) or MBG3 (RR 1.33, 95% CI 1.19-1.49, I 0%); major adverse cardiovascular events (MACEs) in 30 days (RR 0.48, 95% CI 0.27-0.86, I 0%); and MACEs in 180 days (RR 0.41, 95% CI 0.28-0.60, I 0%)].
CONCLUSIONS
We found that PGE1 decreased the occurrence of micro-circulation disturbance in AMI and enhanced the outcome of PCI. Additional studies should be conducted to confirm these findings.
PubMed: 38850398
DOI: 10.1007/s40256-024-00655-3 -
Molecular Nutrition & Food Research Jun 2024Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates...
SCOPE
Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD.
METHODS AND RESULTS
This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1 and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1 mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1 mice. Nobiletin antagonizes the expression of these genes in Bmal1 mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner.
CONCLUSION
Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.
Topics: Animals; Flavones; ARNTL Transcription Factors; Liver Diseases, Alcoholic; Mice, Knockout; Lipogenesis; Proto-Oncogene Proteins c-akt; Male; Liver; Mice, Inbred C57BL; Mice; Protective Agents; Ethanol; Signal Transduction; Apoptosis
PubMed: 38850176
DOI: 10.1002/mnfr.202300833 -
Journal of Molecular and Cellular... Jun 2024An increasing body of evidence suggests a pivotal role for the microvasculature in the development of cardiovascular disease. A dysfunctional coronary microvascular... (Review)
Review
An increasing body of evidence suggests a pivotal role for the microvasculature in the development of cardiovascular disease. A dysfunctional coronary microvascular network, specifically within endothelial cells-the inner most cell layer of vessels-is considered a strong, independent risk factor for future major adverse cardiac events. However, challenges exist with evaluating this critical vascular bed, as many of the currently available techniques are highly invasive and cost prohibitive. The more easily accessible peripheral microcirculation has surfaced as a potential surrogate in which to study mechanisms of coronary microvascular dysfunction and likewise may be used to predict poor cardiovascular outcomes. In this review, we critically evaluate a variety of prognostic, physiological, and mechanistic studies in humans to answer whether the peripheral microcirculation can add insight into coronary microvascular health. A conceptual framework is proposed that the health of the endothelium specifically may link the coronary and peripheral microvascular beds. This is supported by evidence showing a correlation between human coronary and peripheral endothelial function in vivo. Although not a replacement for investigating and understanding coronary microvascular function, the microvascular endothelium from the periphery responds similarly to (patho)physiological stress and may be leveraged to explore potential therapeutic pathways to mitigate stress-induced damage.
PubMed: 38848808
DOI: 10.1016/j.yjmcc.2024.06.002 -
The International Journal of... Jun 2024Many lesions in patients undergoing percutaneous coronary intervention (PCI) exhibit significant calcification. Several techniques have been developed to improve...
Many lesions in patients undergoing percutaneous coronary intervention (PCI) exhibit significant calcification. Several techniques have been developed to improve outcomes in this setting. However, their impact on coronary microcirculation remains unknown. The aim of this study is to evaluate the influence of plaque modification techniques on coronary microcirculation across patients with severely calcified coronary artery disease. In this multicenter retrospective study, consecutive patients undergoing PCI with either Rotablation (RA) or Shockwave-intravascular-lithotripsy (IVL) were included. Primary endpoint was the impairment of coronary microvascular resistances assessed by Δ angiography-derived index of microvascular resistance (ΔIMRangio) which was defined as the difference in IMRangio value post- and pre-PCI. Secondary endpoints included the development of peri procedural PCI complications (flow-limiting coronary dissection, slow-flow/no reflow during PCI, coronary perforation, branch occlusion, failed PCI, stroke and shock developed during PCI) and 12-month follow-up adverse events. 162 patients were included in the analysis. Almost 80% of patients were male and the left descending anterior artery was the most common treated vessel. Both RA and IVL led to an increase in ΔIMRangio (22.3 and 10.3; p = 0.038, respectively). A significantly higher rate of PCI complications was observed in patients with ΔIMRangio above the median of the cohort (21.0% vs. 6.2%; p = 0.006). PCI with RA was independently associated with higher ΔIMRangio values (OR 2.01, 95% CI: 1.01-4.03; p = 0.048). Plaque modification with IVL and RA during PCI increases microvascular resistance. Evaluating the microcirculatory status in this setting might help to predict clinical and procedural outcomes and to optimize clinical results.
PubMed: 38848005
DOI: 10.1007/s10554-024-03152-5 -
Annals of Medicine and Surgery (2012) Jun 2024Kidney damage can result from various factors, leading to structural and functional changes in the kidney. Acute kidney injury (AKI) refers to a sudden decline in kidney... (Review)
Review
INTRODUCTION
Kidney damage can result from various factors, leading to structural and functional changes in the kidney. Acute kidney injury (AKI) refers to a sudden decline in kidney function, while chronic kidney disease involves a gradual deterioration lasting more than 3 months. Mechanisms of renal injury include impaired microcirculation, inflammation, and oxidative stress. Cysteinyl-leukotrienes (CysLTs) are inflammatory substances contributing to tissue damage. Montelukast, a leukotriene receptor antagonist, has shown potential renoprotective effects in experimental models of kidney injury.
METHODS
The authors conducted a scoping review using PubMed, Scopus, and Web of Science databases to identify relevant studies investigating the impact of montelukast on renal diseases. Articles published until 2022 were included and evaluated for quality. Data extraction and analysis were performed based on predetermined inclusion criteria.
RESULTS
The scoping review included 30 studies from 8 countries. Montelukast demonstrated therapeutic effects in various experimental models of nephrotoxicity and AKI induced by agents such as cisplatin, lipopolysaccharide, diclofenac, amikacin, , cyclosporine, methotrexate, cobalt-60 gamma radiation, doxorubicin, and cadmium. Studies involving human subjects with nephrotic syndrome, pyelonephritis, and other renal diseases also reported positive outcomes with montelukast treatment. Montelukast exhibited anti-inflammatory, anti-apoptotic, antioxidant, and neutrophil-inhibiting properties, leading to improved kidney function and histopathological changes.
CONCLUSIONS
Montelukast shows promise as a renoprotective medication, particularly in early-stage kidney injury. Its ability to mitigate inflammation, oxidative stress, and neutrophil infiltration contributes to its therapeutic effects. Further research is needed to explore the clinical applications and mechanisms underlying the renoprotective action of montelukast.
PubMed: 38846849
DOI: 10.1097/MS9.0000000000002085 -
Heliyon Jun 2024Shenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the...
BACKGROUND
Shenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm? inistration timing.
METHODS
Twenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP 'were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed.
RESULTS
SF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group.
CONCLUSIONS
SF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase.
PubMed: 38845930
DOI: 10.1016/j.heliyon.2024.e31377 -
Developmental Neurobiology Jun 2024Visual impairment caused by optic neuropathies is irreversible because retinal ganglion cells (RGCs), the specialized neurons of the retina, do not have the capacity for... (Review)
Review
Visual impairment caused by optic neuropathies is irreversible because retinal ganglion cells (RGCs), the specialized neurons of the retina, do not have the capacity for self-renewal and self-repair. Blindness caused by optic nerve neuropathies causes extensive physical, financial, and social consequences in human societies. Recent studies on different animal models and humans have established effective strategies to prevent further RGC degeneration and replace the cells that have deteriorated. In this review, we discuss the application of electrical stimulation (ES) and magnetic field stimulation (MFS) in optic neuropathies, their mechanisms of action, their advantages, and limitations. ES and MFS can be applied effectively in the field of neuroregeneration.. Although stem cells are becoming a promising approach for regenerating RGCs, the inhibitory environment of the CNS and the long visual pathway from the optic nerve to the superior colliculus are critical barriers to overcome. Scientific evidence has shown that adjuvant treatments, such as the application of ES and MFS help direct thetransplanted RGCs to extend their axons and form new synapses in the central nervous system (CNS). In addition, these techniques improve CNS neuroplasticity and decrease the inhibitory effects of the CNS. Possible mechanisms mediating the effects of electrical current on biological tissues include the release of anti-inflammatory cytokines, improvement of microcirculation, stimulation of cell metabolism, and modification of stem cell function. ES and MFS have the potential to promote angiogenesis, direct axon growth toward the intended target, and enhance appropriate synaptogenesis in optic nerve regeneration.
PubMed: 38844425
DOI: 10.1002/dneu.22949 -
Experimental Eye Research Jun 2024Clouding of the eye lens or cataract is an age-related anomaly that affects middle-aged humans. Exploration of the etiology points to a great extent to oxidative stress...
Clouding of the eye lens or cataract is an age-related anomaly that affects middle-aged humans. Exploration of the etiology points to a great extent to oxidative stress due to different forms of reactive oxygen species/metabolites such as Hydrogen peroxide (HO) that are generated due to intracellular metabolism and environmental factors like radiation. If accumulated and left unchecked, the imbalance between the production and degradation of HO in the lens could lead to cataracts. Our objective was to explore ex vivo the effects of HO on lens physiology. We investigated transparency, intracellular pH (pH), intercellular gap junction coupling (GJC), hydrostatic pressure (HP) and membrane water permeability after subjecting two-month-old C57 wild-type (WT) mouse lenses for 3 h or 8 h in lens saline containing 50 μM HO; the results were compared with control lenses incubated in the saline without HO. There was a significant decrease in lens transparency in HO-treated lenses. In control lenses, pH decreases from ∼7.34 in the surface fiber cells to 6.64 in the center. Experimental lenses exposed to HO for 8 h showed a significant decrease in surface pH (from 7.34 to 6.86) and central pH (from 6.64 to 6.56), compared to the controls. There was a significant increase in GJC resistance in the differentiating (12-fold) and mature (1.4-fold) fiber cells compared to the control. Experimental lenses also showed a significant increase in HP which was ∼2-fold higher at the junction between the differentiating and mature fiber cells and ∼1.5-fold higher at the center compared to these locations in control lenses; HP at the surface was 0 mm Hg in either type lens. Fiber cell membrane water permeability significantly increased in HO-exposed lenses compared to controls. Our data demonstrate that elevated levels of lens intracellular HO caused a decrease in intracellular pH and led to acidosis which most likely uncoupled GJs, and increased AQP0-dependent membrane water permeability causing a consequent rise in HP. We infer that an abnormal increase in intracellular HO could induce acidosis, cause oxidative stress, alter lens microcirculation, and lead to the development of accelerated lens opacity and age-related cataracts.
PubMed: 38843983
DOI: 10.1016/j.exer.2024.109957 -
The Journal of Endocrinology Aug 2024Characteristic symptoms of hyperthyroidism include weight loss, heart palpitation, and sweating. Thyroid hormones (TH) can stimulate thermogenesis through central and...
Characteristic symptoms of hyperthyroidism include weight loss, heart palpitation, and sweating. Thyroid hormones (TH) can stimulate thermogenesis through central and peripheral mechanisms. Previous studies have shown an association between dysfunction of cardiotrophin-like cytokine factor 1 (CLCF1) and cold-induced sweating syndrome, with recent research also indicating a link between CLCF1 and brown adipose tissue thermogenesis. However, it remains unclear whether CLCF1 and TH have synergistic or antagonistic effects on thermogenesis. This study aims to investigate the influence of thyroid hormone on circulating CLCF1 levels in humans and explore the potential possibilities of thyroid hormone in regulating energy metabolism by modulating Clcf1 in mice. By recruiting hyperthyroid patients and healthy subjects, we observed significantly lower serum CLCF1 levels in hyperthyroid patients compared to healthy subjects, with serum CLCF1 levels independently associated with hyperthyroidism after adjusting for potential confounders. Tissue analysis from mice treated with T3 revealed a decrease in CLCF1 expression in BAT and iWAT of C57BL/6 mice. These findings suggest that TH may play a role in regulating CLCF1 expression in adipose tissue.
Topics: Hyperthyroidism; Animals; Male; Triiodothyronine; Humans; Mice; Adult; Female; Mice, Inbred C57BL; Middle Aged; Adipose Tissue, Brown; Cytokines; Thermogenesis; Case-Control Studies
PubMed: 38842921
DOI: 10.1530/JOE-23-0412 -
Current Opinion in Critical Care Aug 2024We review the current Society for Cardiovascular Angiography and Interventions (SCAI) cardiogenic shock classification system and consider alternatives or iterations... (Review)
Review
PURPOSE OF REVIEW
We review the current Society for Cardiovascular Angiography and Interventions (SCAI) cardiogenic shock classification system and consider alternatives or iterations that may enhance our current descriptions of cardiogenic shock trajectory.
RECENT FINDINGS
Several studies have identified the potential prognostic value of serial SCAI stage re-assessment, usually within the first 24 h of shock onset, to predict deterioration and clinical outcomes across shock causes. In parallel, numerous registry-based analyses support the utility of a more precise assessment of the macrocirculation and microcirculation, leveraging invasive haemodynamics, imaging and additional laboratory and clinical markers. The emergence of machine learning and artificial intelligence capabilities offers the opportunity to integrate multimodal data into high fidelity, real-time metrics to more precisely define trajectory and inform our therapeutic decision making.
SUMMARY
Whilst the SCAI staging system remains a pivotal tool in cardiogenic shock assessment, communication and reassessment, it is vital that the sophistication with which we measure and assess shock trajectory evolves in parallel our understanding of the complexity and variability of clinical course and clinical outcomes.
Topics: Humans; Shock, Cardiogenic; Prognosis; Hemodynamics; Societies, Medical
PubMed: 38841918
DOI: 10.1097/MCC.0000000000001168