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Progress in Molecular Biology and... 2024Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are... (Review)
Review
Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are several types of CVDs like stroke, endothelial dysfunction, thrombosis, atherosclerosis, plaque instability and heart failure. Identification of a new drug for heart disease takes longer duration and its safety efficacy test takes even longer duration of research and approval. This chapter explores drug repurposing, nano-therapy, and plant-based treatments for managing CVDs from existing drugs which saves time and safety issues with testing new drugs. Existing drugs like statins, ACE inhibitor, warfarin, beta blockers, aspirin and metformin have been found to be useful in treating cardiac disease. For better drug delivery, nano therapy is opening new avenues for cardiac research by targeting interleukin (IL), TNF and other proteins by proteome interactome analysis. Nanoparticles enable precise delivery to atherosclerotic plaques, inflammation areas, and damaged cardiac tissues. Advancements in nano therapeutic agents, such as drug-eluting stents and drug-loaded nanoparticles are transforming CVDs management. Plant-based treatments, containing phytochemicals from Botanical sources, have potential cardiovascular benefits. These phytochemicals can mitigate risk factors associated with CVDs. The integration of these strategies opens new avenues for personalized, effective, and minimally invasive cardiovascular care. Altogether, traditional drugs, phytochemicals along with nanoparticles can revolutionize the future cardiac health care by identifying their signaling pathway, mechanism and interactome analysis.
Topics: Humans; Drug Repositioning; Drug Discovery; Animals; Heart Diseases
PubMed: 38942536
DOI: 10.1016/bs.pmbts.2024.02.001 -
Pharmacological Research Jun 2024Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a... (Review)
Review
Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.
PubMed: 38942341
DOI: 10.1016/j.phrs.2024.107281 -
European Journal of Pharmacology Jun 2024Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, which endothelial-to-mesenchymal transition (EndMT) being its main progressive phase....
Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, which endothelial-to-mesenchymal transition (EndMT) being its main progressive phase. Wogonin, a flavonoid extracted from the root of Scutellaria baicalensis Georgi, hinders the abnormal proliferation of cells and has been employed in the treatment of several cardiopulmonary diseases. This study was designed to investigate how wogonin affected EndMT during PH. Monocrotaline (MCT) was used to induce PH in rats. Binding capacity of TGF-β1 receptor to wogonin detected by molecular docking and molecular dynamics. EndMT model was established in pulmonary microvascular endothelial cells (PMVECs) by transforming growth factor beta-1 (TGF-β1). The result demonstrated that wogonin (20 mg/kg/day) attenuated right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular thickness in PH rats. EndMT in the pulmonary vascular was inhibited after wogonin treatment as evidenced by the restored expression of CD31 and decreased expression of α-SMA. Wogonin has strong affinity for both TGFBRI and TGFBRII, and has a better binding stability for TGFBRI. In TGF-β1-treated PMVECs, wogonin (0.3, 1, and 3 μM) exhibited significant inhibitory effects on this transformation process via down-regulating the expression of p-Smad2 and Snail, while up-regulating the expression of p-Smad1/5. Additionally, results of western blot and fluorescence shown that the expression of α-SMA were decrease with increasing level of CD31 in PMVECs. In conclusion, our research showed that wogonin suppressed EndMT via the TGF-β1/Smad pathway which may lead to its alleviated effect on PH. Wogonin may be a promising drug against PH.
PubMed: 38942264
DOI: 10.1016/j.ejphar.2024.176786 -
Journal of Affective Disorders Jun 2024Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on...
BACKGROUND
Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on short-term HRV, with limited exploration of the 24-h HRV circadian rhythm, despite its ability to comprehensively capture overall HRV distribution and dynamic fluctuations. In this study, we investigated the circadian rhythms of 24-h HRV indices in patients with MDD and their associations with symptom severity.
METHODS
We recorded 24-h electrocardiograms in 73 patients with MDD (53 in major depressive episode and 20 in remission period) and 31 healthy controls. An extended cosine model was used to model the circadian rhythm of six HRV indices by five parameters: the mesor, amplitude, duty cycle, curve smoothness, and acrophase. Symptom severity was evaluated using the Hamilton Depression Scale and Hamilton Anxiety Scale.
RESULTS
Compared with the control group, patients with MDD had a significantly smaller SampEn mesor, higher HF duty cycle, and lower heart rate (HR) duty cycle. They also had a significantly higher curve smoothness for HR, RMSSD, and HF. The mesor for SampEn, along with the curve smoothness for HR and ln RMSSD, were associated with certain symptoms in patients with MDD.
LIMITATIONS
The cross-sectional design and psychiatric treatment of most patients with MDD limited our findings.
CONCLUSION
Patients with MDD exhibit abnormal HRV circadian rhythms that are associated with symptoms. Moreover, 24-h ECG monitoring may potentially serve as an adjunct value to objectively evaluate clinical symptoms in these patients.
PubMed: 38942206
DOI: 10.1016/j.jad.2024.06.102 -
Ageing Research Reviews Jun 2024Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by loss of dopaminergic neurons in the substantia nigra, as well as the... (Review)
Review
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by loss of dopaminergic neurons in the substantia nigra, as well as the abnormal accumulation of misfolded α-synuclein. Clinically, PD is featured by typical motor symptoms and some non-motor symptoms. Up to now, although considerable progress has been made in understanding the pathogenesis of PD, there is still no effective therapeutic treatment for the disease. Thus, exploring new therapeutic strategies has been a topic that needs to be addressed urgently. Noteworthy, with the proposal of the microbiota-gut-brain axis theory, antimicrobial drugs have received significant attention due to their effects on regulating the intestinal microbiota. Nowadays, there is growing evidence showing that some antimicrobial drugs may be promising drugs for the treatment of PD. Data from pre-clinical and clinical studies have shown that some antimicrobial drugs may play neuroprotective roles in PD by modulating multiple biochemical and molecular pathways, including reducing α-synuclein aggregation, inhibiting neuroinflammation, regulating mitochondrial structure and function, as well as suppressing oxidative stress. In this paper, we summarized the effects of some antimicrobial drugs on PD treatment from recent pre-clinical and clinical studies. Then, we further discussed the potential of a few antimicrobial drugs for treating PD based on molecular docking and molecular dynamics simulation. Importantly, we highlighted the potential of clorobiocin as the therapeutic strategy for PD owing to its ability to inhibit α-synuclein aggregation. These results will help us to better understand the potential of antimicrobial drugs in treating PD and how antimicrobial drugs may alleviate or reverse the pathological symptoms of PD.
PubMed: 38942200
DOI: 10.1016/j.arr.2024.102387 -
Gene Jun 2024This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473...
This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VI), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VI, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.
PubMed: 38942180
DOI: 10.1016/j.gene.2024.148727 -
The American Journal of the Medical... Jun 2024Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of > 1.4 kg from morning to night, increasing edema,... (Review)
Review
Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of > 1.4 kg from morning to night, increasing edema, increasing truncal and abdominal girth with bloating when assuming an upright position and nocturia that is unrelated to menses. There is an increase in morbidity but not mortality. Increased capillary membrane leakage appears to be the underlying pathophysiologic abnormality that explains the myriad of clinical presentations. We present 2 cases of life-threatening complications of IE that resulted in seizures related to acute hyponatremia in one and extreme postural dizziness and fainting induced by postural hypotension in the other. The first patient was successfully treated with salt restriction, timely use of furosemide and limitation of water intake; the other was successfully treated by use of support hose. Treatment of these patients required a fundamental understanding of the intricate pathophysiological consequences of a leaky capillary membrane, an understanding of Starling forces and detailing the effectiveness of a low salt diet, use of diuretics and limited water intake in one and why support hose would be beneficial in the other patient. Both patients experienced significant physical and emotional benefits that substantially improved quality of life.
PubMed: 38942171
DOI: 10.1016/j.amjms.2024.06.024 -
Journal of Ethnopharmacology Jun 2024The traditional medicinal formulation, Qifu-yin (QFY), has been widely prescribed for Alzheimer's disease (AD) treatment in China, yet the comprehensive mechanisms...
ETHNOPHARMACOLOGICAL RELEVANCE
The traditional medicinal formulation, Qifu-yin (QFY), has been widely prescribed for Alzheimer's disease (AD) treatment in China, yet the comprehensive mechanisms through which QFY mitigates AD pathology remain to be fully delineated.
AIM OF THE STUDY
This study aimed to explore the therapeutic implications of QFY on the synaptic injury and oxidative stress in the hippocampus of APPswe/PS1dE9 (APP/PS1) mice, with a concerted effort to elucidate the molecular mechanisms related to synaptic preservation and memory improvement.
MATERIALS AND METHODS
The components of QFY were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The neuroprotective effects of QFY was evaluated using six-month-old male APP/PS1 mice. Subsequent to a 15 days of QFY regimen, spatial memory was assessed utilizing the Morris water maze (MWM) test. Amyloid-beta (Aβ) aggregation was detected via immunostaining, while the quantification of Aβ and Aβ was achieved through enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to investigate the synaptic structure and mitochondrial morphology. Golgi staining was applied to examine dendritic spine density. Reactive oxygen species (ROS), 3-nitrotyrosine (3-NT) and 4-hydroxy-nonenal (4-HNE) assays were employed to assess oxidative stress. The expression profiles of Aβ metabolism-associated enzymes and the Keap1/Nrf2/ARE signaling pathway were determined by Western blot.
RESULTS
A total of 20 principal compounds in QFY were identified. QFY mitigated memory deficits of APP/PS1 mice, including reducing escape latency and search distance and increasing the time and distance spent in the target quadrant. In addition, QFY increased platform crossings of APP/PS1 mice in the probe trial of MWM tests. TEM analysis showed that QFY increased synapse number in the CA1 region of APP/PS1 mice. Further studies indicated that QFY elevated the expression levels of Post synaptic density protein 95 (PSD95) and synaptophysin, and mitigated the loss of dendritic spine density in the hippocampus of APP/PS1 mice. QFY has been shown to ameliorated the structural abnormalities of mitochondria, including mitochondrial dissolution and degradation, up-regulate ATP synthesis and membrane potential in the hippocampus of APP/PS1 mice. Moreover, QFY activated the Keap1/Nrf2/ARE signaling pathway in the hippocampus of APP/PS1 mice, which might contribute to the neuroprotective effects of QFY.
CONCLUSION
QFY activates the Keap1/Nrf2/ARE signaling, and protects against synaptic and mitochondrial dysfunction in APP/PS1 mice, proposing a potential alternative therapeutic strategy for AD management.
PubMed: 38942156
DOI: 10.1016/j.jep.2024.118497 -
Clinics in Dermatology Jun 2024Frontal fibrosing alopecia (FFA) is characterized by a receding hairline in the frontotemporal region due to the gradual loss of hair follicles and then follicular stem...
Frontal fibrosing alopecia (FFA) is characterized by a receding hairline in the frontotemporal region due to the gradual loss of hair follicles and then follicular stem cells and follicular fibrosis. Follicular stem cells are crucial in skin healing after chemical peeling and other resurfacing procedures. Although there is a possible association of FFA with a history of facial and scalp surgical procedures, there is no information on the safety of cosmetic procedures in patients with FFA. We report five patients with FFA who experienced unusual and complicated outcomes after undergoing a deep chemical peel (phenol and croton oil). As the prevalence of FFA continues to increase globally, it is essential to raise awareness about the potential incompatibility of this dermatologic disorder with specific cosmetic procedures, such as deeper peels and other resurfacing modalities.
PubMed: 38942154
DOI: 10.1016/j.clindermatol.2024.06.024 -
British Journal of Hospital Medicine... Jun 2024Although electromyography has been extensively used in the diagnosis of neurological diseases, there is no comprehensive understanding of the electromyography...
Specific electromyography characteristics can distinguish longitudinally extensive transverse myelitis from congestive myelopathy due to spinal dural arteriovenous fistula: a retrospective study.
Although electromyography has been extensively used in the diagnosis of neurological diseases, there is no comprehensive understanding of the electromyography manifestations of spinal dural arteriovenous fistula. Given the widespread use of electromyography in the diagnosis of neurological conditions, it is worthwhile to holistically analyse the electromyography findings of spinal dural arteriovenous fistula to differentiate it from neurological diseases that share similar clinical manifestations. The aim of this study is to evaluate whether electromyography can distinguish spinal dural arteriovenous fistula from longitudinally extensive transverse myelitis. We holistically reviewed files of all patients who were diagnosed with spinal dural arteriovenous fistula or longitudinally extensive transverse myelitis at The First Medical Centre of PLA General Hospital from 1 January 2010 to 31 December 2020. We compared the symptomology, epidemiology, and imaging results of patients with spinal dural arteriovenous fistula and longitudinally extensive transverse myelitis, placing emphasis on their electromyography manifestations. Student's t test was used to analyse normally distributed data, while Chi-square test was used to compare classification statistics. Lesions of spinal dural arteriovenous fistula shown on images tend to appear at lower lumbar and sacral segments, whereas lesions of the cervical and upper thoracic segments are more characteristic of longitudinally extensive transverse myelitis. Spinal dural arteriovenous fistula patients and longitudinally extensive transverse myelitis patients overlap in terms of clinical manifestations. After comparison, the two groups of patients had different demographics (age, sex), onset mode, predisposing factors before onset, and electromyographic features. The electromyographic features of patients with spinal dural arteriovenous fistula were associated with neurogenic damage ( < 0.001). In patients with spinal dural arteriovenous fistula, electromyography can help clinicians to identify early disease, avoid patient treatment delay, and eliminate unnecessary treatment.
Topics: Humans; Electromyography; Male; Female; Myelitis, Transverse; Central Nervous System Vascular Malformations; Retrospective Studies; Middle Aged; Adult; Aged; Diagnosis, Differential; Spinal Cord Diseases; Magnetic Resonance Imaging
PubMed: 38941974
DOI: 10.12968/hmed.2024.0111