Pathophysiological Effects Research Articles

Endothelial-Protective Actions of Diethylether Extract from Gentiana kochiana and Xanthone Gentiacaulein Against Oxidized LDL-Induced Injury—In Vitro Evaluation

Endothelial dysfunction is an early pathophysiological event in atherosclerosis. The endothelial-protective abilities of diethylether extract (EE) from the Gentiana kochiana (Gentianaceae) herb and its main component, xanthone aglycone gentiacaulein (GC), were evaluated in an oxidized low-density lipoprotein (oxLDL)-treated EA.hy926 endothelial cell line. The EE and GC actions were assessed using cell viability assays, flow cytometry, immunoblot, DPPH, NBT, TBARS, conjugated diene formation, and Griess tests. Both EE and GC prevented oxLDL-induced apoptosis by reducing intracellular reactive oxygen species levels, mitochondrial depolarization, and caspase activation in EA.hy926 cells. EE and GC dose-dependently diminished oxLDL-induced cellular lipid peroxidation. In cell-free conditions, EE moderately scavenged superoxide anions and had no affinity toward DPPH radicals, GC did not interact with either of investigated free radicals, while both EE and GC effectively delayed Cu²⁺-induced LDL oxidation. EE and GC upregulated oxLDL-suppressed protective Akt/CREB/eNOS and ERK signals and restored oxLDL-reduced nitric oxide levels. Therefore, EE and GC effectively counteract oxLDL-induced endothelial apoptosis by reducing oxidative stress, promoting mitochondrial recovery, and enhancing the prosurvival Akt/CREB/eNOS axis and ERK activity. Our study is the first to demonstrate that xanthone-rich EE from aerial parts of G. kochiana and xanthone GC alleviate oxLDL-induced endothelial cell injury, underscoring their potential for cardiovascular protection.

Dermatological Manifestations of COVID-19: A Comprehensive Review

Background:COVID-19, caused by SARS-CoV-2, manifests in multiple organ systems, including the skin, presenting a range of dermatologic symptoms. Recognizing these cutaneous signs is essential, as they often appear early or alongside respiratory symptoms, aiding in diagnosis and management. Key skin manifestations include pernio-like lesions (COVID toes), maculopapular rashes, urticarial eruptions, vesicular lesions, and vascular-related signs, each potentially valuable for prognostic assessment. Methods:A systematic review of major databases, including PubMed, Google Scholar, Scopus, and Web of Science, was conducted. Studies published between 2015 and 2024 were included, focusing on the prevalence, pathophysiology, and clinical significance of COVID-19-related skin lesions. Selection criteria prioritized case reports, case series, cohort studies, and systematic reviews reporting quantitative data on cutaneous presentations. Main Findings:COVID-19-associated dermatologic symptoms vary in prevalence and severity, with maculopapular rashes and COVID toes being among the most common. Notably, vascular lesions are linked to severe cases and may serve as indicators of coagulopathy or cytokine storms. Cutaneous signs can often precede or appear in the absence of respiratory symptoms, offering clinicians a window for early detection. Histopathological findings reveal immune-mediated mechanisms, suggesting skin lesions could signal systemic inflammation in COVID-19. Conclusion:The diverse skin manifestations of COVID-19 underscore the need for dermatologic assessment in patient care. These findings support the integration of dermatology into COVID-19 care teams, especially for severe cases, where skin signs may correlate with systemic complications. Further research on pathophysiology and long-term effects is essential for advancing diagnostic and prognostic approaches, reinforcing the role of dermatologic indicators in comprehensive COVID-19 management.

In Vivo Measurement of Intestinal Permeability to Macromolecules in Adult Zebrafish (Danio rerio).

Intestinal permeability plays a crucial role in intestinal barrier function. Altered intestinal permeability is well documented in numerous chronic diseases and may serve as a risk factor for disease onset as well as a target for innovative therapeutic strategies. While reliable and sensitive approaches for studying intestinal permeability have been established in animal models, such as mice and zebrafish larvae, methods for investigating this in adult zebrafish remain a considerable challenge. The zebrafish has emerged as a valuable model for studying intestinal development, physiology, and disease. Moreover, zebrafish offer certain advantages over rodent models, such as the ability to evaluate the dynamic interactions of labeled markers invivo and in real time. In this study, we present a comprehensive pipeline for assessing invivo intestinal permeability in adult zebrafish using fluorescent-labeled dextran. Detailed protocols for fish handling, reagent preparation, optimization of reagent dosage and delivery routes, and quantification of fluorescent markers in extraintestinal sites are provided. Our findings suggest that zebrafish hold promise as an alternative model for invivo investigations of intestinal permeability induced by genetic, pathophysiological, and/or pharmacological events.

The IL-4-IL-4Rα axis modulates olfactory neuroimmune signaling to induce loss of smell.

IL-4 and IL-13 have non-redundant effects in olfaction, with loss of smell in mice evoked only by intranasal administration of IL-4, but not IL-13. IL-4-evoked pathophysiological effects on olfaction is independent of compromised structural integrity of the olfactory neuroepithelium. IL-4-IL-4Rα signaling modulates neuronal crosstalk with immune cells, suggesting a functional link between olfactory impairment and neuroinflammation. Abbreviations: IL, interleukin; KO, knock-out; wk, week; WT, wild-type.

Physicochemical Characterization of Hyaluronic Acid-Methylcellulose Semi-Gels for Mitochondria Transplantation.

Traumatic spinal cord injury (SCI) presents a significant medical challenge due to its intricate nature and treatment complexities. SCI can cause physical impairments by affecting neural and motor functions as well as initiating a series of pathophysiological events exacerbating the initial trauma. Leakage from ruptured neurons and vessels disrupt ionic balance and induces excitotoxicity, leading to progressive cellular degeneration. Introducing mitochondria to the SCI lesion has shown potential in attenuating secondary injury. Mitochondria transplantation improves cellular bioenergetics and reduces concentration of reactive oxygen species achieving homeostasis and neuroprotection. Nonetheless, keeping mitochondria viable outside cell environment for a time longer than a few minutes proves to be challenging. Additionally, localized delivery to the injury site has also been limited by other factors including flow rate of cerebrospinal fluid that washes away mobilized organelle from the compromised tissue site. Previously we showed that using hyaluronic acid-methylcellulose semi-gels (HAMC) as a biocompatible, erodible thermogelling delivery vehicle helped to overcome some of these challenges. HAMC allows for controlled release at and around the injury site, utilizing the reverse thermogelling property of MC. Sustained release of mitochondria at slower rate can increase their uptake in spinal tissue. To better optimize the semi-gel delivery of mitochondria requires a more complete understanding of the physicochemical properties of the HAMC semi-gels. We have used ultraviolet-visible spectroscopy to measure optical density of HAMC semi-gels for different HA to MC ratios and examine the temperature dependent gelation properties above their low critical solution temperature (LCST). The viscosity and degree of crystallinity of the resulting HAMC semi-gels were also assessed. Semi-gel erosion and mitochondrial release over time were studied using a fluorescence microplate reader. Lastly, seahorse assay was used to study released mitochondria respiration and viability after incubation in HAMC semi-gel.

Epilepsy Genetics.

This article reviews essential concepts and terminology in epilepsy genetics, discusses current guidance on when and how to pursue genetic evaluation, provides an overview of genetic syndromes, and offers illustrative examples of the effect of genetic diagnosis in epilepsy patient care. The growing availability of next-generation genetic sequencing methods for clinical use provides an opportunity to make etiologic diagnoses in a larger number of epilepsy patients, which can affect therapeutic management, prognostic counseling, surveillance for comorbid conditions, and other aspects of epilepsy care. Exome and genome sequencing may have high diagnostic yields in patients with unexplained epilepsy. The body of knowledge in epilepsy genetics is growing more complex, not only because of gene discovery but also because of an increasingly nuanced understanding of the varying pathophysiologic effects of specific types of variation within epilepsy genes. Genetic testing plays a key role in the evaluation of epilepsy patients. Clinicians caring for patients with epilepsy should understand patient selection, test selection, and result interpretation in genetic testing. The recommended first-line test in most patients is exome or genome sequencing.

The protective role of ethanolic extract of ginseng (Panax ginseng) against adverse physiological and histological alterations in the liver of female rabbits exposed to chlorine

Background: Ginseng (Panax ginseng) has garnered considerable attention due to its medicinal properties. This study aimed to assess the protective effects of ginseng ethanolic extract against chlorine-induced toxicity in female rabbits. .Methods: Thirty-two female rabbits were randomly divided into four groups: a negative control group receiving chlorine-free water, a positive control group receiving tap water with chlorine (0.05 ppm/L), a group exposed to chlorine (5 ppm/L) in water, and a group exposed to chlorine (5 ppm/L) along with ethanolic ginseng extract (200 mg/kg body weight). Treatment lasted for four weeks.Results: revealed that oral exposure to chlorine led to oxidative stress, evidenced by elevated levels of malondialdehyde (MDA) and liver enzymes (AST & ALT), as well as suppressed blood parameters (PCV, HB, and RBC count), and histological liver alterations compared to the normal control group. Conversely, administration of ginseng extracts alongside chlorine for four weeks reduced MDA levels and liver enzyme activity while enhancing blood parameters, accompanied by decreased inflammatory histological changes.Conclusion: These findings suggest that ginseng extract possesses potent antioxidant activity, mitigating chlorine-induced toxicity and its associated pathophysiological consequences. Keywords: Ginseng; Chlorine; MDA; Liver enzymes; Blood parameters

State of precision medicine for heart failure with preserved ejection fraction in a new therapeutic age.

Heart failure with preserved ejection fraction (HFpEF) is defined by heart failure (HF) with a left ventricular ejection fraction (LVEF) of at least 50%. HFpEF has a complex and heterogeneous pathophysiology with multiple co-morbidities contributing to its presentation. Establishing the diagnosis of HFpEF can be challenging. Two algorithms, the 'Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension, Elderly age >60, elevated Filling pressures' (H2FPEF) and the 'Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology' (HFA-PEFF), can help to determine the likelihood of HFpEF in individuals with symptoms of HF. Phenotype clusters defined largely by the total number and types of co-morbidities may delineate groups of patients with HFpEF with different management needs. It is important to recognize alternative diagnoses or HFpEF mimics such as infiltrative cardiomyopathies, coronary artery disease, lung disease, anxiety, depression, anaemia, severe obesity, and physical deconditioning, among others. Treatment with sodium-glucose co-transporter 2 inhibitors (dapagliflozin and empagliflozin) is recommended for all patients with HFpEF unless contraindicated. Future research should consider alternative approaches to guide the initial diagnosis and treatment of HFpEF, including phenotype clustering models and artificial intelligence, and consider whether LVEF is the most useful distinguishing feature for categorizing HF. Ongoing clinical trials are evaluating novel pharmacological and device-based approaches to address the pathophysiological consequences of HFpEF.

Effects of MeCP2 on chronic seizures and cognitive function in mice with temporal lobe epilepsy.

Mutations in methyl CpG binding protein 2 (MeCP2) are linked to Rett syndrome, in which epilepsy is one of the most well-described disorders. However, little is known about the specific role of MeCP2 during epileptogenesis. Our previous study has demonstrated that MeCP2 has a unique control on the development of mossy fiber sprouting (MFS) in the epileptic hippocampus. This study aimed to (1) examine whether MeCP2 affects spontaneous recurrent seizures (SRSs) and cognitive deficits in mice with pilocarpine-induced epilepsy, and (2) profile MeCP2's downstream molecular events. In the dentate gyrus (DG), we found that over-expression or suppression of MeCP2 significantly reduced or increased the frequency, duration, and number of stage 5 seizures of SRSs during the chronic stage after the SE. Over-expression of MeCP2 improved cognitive deficits in TLE mice, while exacerbated cognitive performances were observed following MeCP2 knockdown. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-sequence analyses revealed that MeCP2-targeted genes have far‑reaching impacts on the pathophysiological events during epileptogenesis, including neuron differentiation, neurogenesis, axon guidance, and so on.

Electroencephalographic markers in Major Depressive Disorder: insights from absolute, relative power, and asymmetry analyses.

Major Depressive Disorder (MDD) leads to dysfunction and impairment in neurological structures and cognitive functions. Despite extensive research, the pathophysiological mechanisms and effects of MDD on the brain remain unclear. This study aims to assess the impact of MDD on brain activity using EEG power spectral analysis and asymmetry metrics. EEG recordings were obtained from 48 patients with MDD and 78 healthy controls. The data were segmented into 2-second windows (1024 data points) and analyzed using the Welch method, an advanced variant of the Fast Fourier Transform (FFT). A Hanning time window with 50% overlap was applied to compute the modified periodogram. Absolute and relative power, along with asymmetry values in the theta, alpha, and beta frequency bands, were calculated. Patients with MDD exhibited significantly higher absolute and relative power in the theta and beta bands and decreased power in the alpha band compared to healthy controls. Asymmetry analysis revealed significant differences between symmetric channels in the theta band (F7-F8, C3-C4, T3-T4, T5-T6), alpha band (F7-F8, C3-C4, T3-T4, T5-T6, O1-O2), and beta band (C3-C4, T3-T4, T5-T6, P3-P4). The findings suggest that MDD affects brain mechanisms and cognitive functions, as evidenced by altered power values in the theta and alpha bands. Additionally, asymmetry values in theta, alpha, and beta bands may serve as potential biomarkers for MDD. This study highlights that beyond the commonly used alpha asymmetry, theta and beta asymmetry can also provide valuable insights into the neurophysiological effects of MDD, aligning with previous neuroimaging studies that indicate impairments in memory, attention, and neuroanatomical connectivity in MDD.

L-type Calcium Channel Blockade Worsens Glucose Tolerance and β-Cell Function in C57BL6/J Mice Exposed to Intermittent Hypoxia.

Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated. Adult male C57BL6/J mice were exposed to either nifedipine or vehicle concurrently with IH or intermittent air (IA) over five days. IH exposure entailed cycling fractional inspired oxygen levels between 0.21 and 0.055 at a rate of 60 events per hour. Nifedipine (20 mg/kg/day) or vehicle was administered via subcutaneous osmotic pumps resulting in four groups of mice: IA-vehicle (control), IA-nifedipine, and IH-vehicle, IH-nifedipine. Compared to IA (control), IH increased fasting glucose (Mean Δ:33.0 mg/dl; p<0.001) and insulin (mean Δ: 0.53 ng/ml; p<0.001) with nifedipine having no independent effect. Furthermore, glucose tolerance was worse with nifedipine alone, and IH further exacerbated the impairment in glucose disposal (p=0.013 for interaction). Nifedipine also decreased glucose-stimulated insulin secretion and the insulinogenic index, with addition of IH attenuating those measures further. There were no discernible alterations in insulin biosynthesis/processing, insulin content, or islet morphology. These findings underscore the detrimental impact of IH on insulin sensitivity and glucose tolerance, while highlighting that nifedipine exacerbates these disturbances through impaired β- cell function. Consequently, cautious use of L-type calcium channel blockers is warranted in OSA patients, particularly in those at risk for type 2 diabetes.

Infants of diabetic mothers: epidemiology, pathophysiology, fetal heartassessment, structural and functional heart consequences: A narrative review.

Infants of diabetic mothers are neonates born to a woman who had periodic hyperglycaemia during pregnancy. Consequently, infants of diabetic mothers are at higher risks of illness besides morbidity and mortality due to teratogenic effects on the fetal cardiovascular system, causing most frequent CHDs. The primary purpose of this review is to present, on this topic, a better-comprehended review covering pertinent material and data to be informed of severe risks to a newborn's cardiac system and function. These conditions can affect maternal, fetal, neonatal, and future adult health. Further research should be addressed towards the early detection of diabetes, its magnitude, and management. Immediate interventions should be proposed to lessen the diabetes burden and its adversative effects during the prenatal period.

L-type calcium channel blockade worsens glucose tolerance and β-cell function in C57BL6/J mice exposed to intermittent hypoxia.

Intermittent hypoxemia (IH), a pathophysiologic consequence of obstructive sleep apnea (OSA), adversely affects insulin sensitivity, insulin secretion, and glucose tolerance. Nifedipine, an L-type calcium channel blocker frequently used for the treatment of hypertension, can also impair insulin sensitivity and secretion. However, the cumulative and interactive repercussions of IH and nifedipine on glucose homeostasis have not been previously investigated. Adult male C57BL6/J mice were exposed to either nifedipine or vehicle concurrently with IH or intermittent air (IA) over 5 days. IH exposure entailed cycling fractional-inspired oxygen levels between 0.21 and 0.055 at a rate of 60 events/h. Nifedipine (20 mg/kg/day) or vehicle was administered via subcutaneous osmotic pumps resulting in four groups of mice: IA-vehicle (control), IA-nifedipine, IH-vehicle, and IH-nifedipine. Compared with IA (control), IH increased fasting glucose (mean Δ: 33.0 mg/dL; P < 0.001) and insulin (mean Δ: 0.53 ng/mL; P < 0.001) with nifedipine having no independent effect. Furthermore, glucose tolerance was worse with nifedipine alone, and IH further exacerbated the impairment in glucose disposal (P = 0.013 for interaction). Nifedipine also decreased glucose-stimulated insulin secretion and the insulinogenic index, with addition of IH attenuating those measures further. There were no discernible alterations in insulin biosynthesis/processing, insulin content, or islet morphology. These findings underscore the detrimental impact of IH on insulin sensitivity and glucose tolerance while highlighting that nifedipine exacerbates these disturbances through impaired β-cell function. Consequently, cautious use of L-type calcium channel blockers is warranted in patients with OSA, particularly in those at risk for type 2 diabetes.NEW & NOTEWORTHY The results of this study demonstrate the interaction between intermittent hypoxemia (IH) and nifedipine in a murine model. IH raises fasting glucose and insulin levels, with nifedipine exacerbating these disturbances. Glucose tolerance worsens when nifedipine is administered alone, and IH magnifies the impairment in glucose disposal. These findings raise the possibility of potential deleterious effects of L-type calcium channel blockers in patients with obstructive sleep apnea (OSA).

Pathophysiological effects of hypoxia on testis function and spermatogenesis

Pathophysiological effects of hypoxia on testis function and spermatogenesis

Imino and Thioureidic Derivatives as New Tools for Alzheimer's Disease: Preliminary Studies.

Alzheimer's disease is a neurodegenerative chronic disease with a severe social and economic impact in the societies, which still lacks an efficient therapy. Several pathophysiological events (β-amyloid [Aβ] deposits, τ-protein aggregation, loss of cholinergic activity, and oxidative stress) occurs in the progression of the disease. Therefore, the search for efficient multi-targeted agents for the treatment of Alzheimer's disease becomes indispensable. In this paper we evaluated the AChE inhibition by Ellman's method and antioxidant activity by DPPH assay of nine synthetic compounds: two hydroxy-benzene derivatives (1 and 2), three bis-thioureidic derivatives (3-5), two imidazole derivatives (6 and 7), and two phenylacetamide derivatives (8 and 9). The compound 2, (3s,5s,7s)-adamantan-1-yl 4-(((E)-2,5-dihydroxybenzylidene)amino)benzoate, exhibited the best antioxidant activity (30.00 ± 1.05 μM eq Trolox) and compound 4 showed the highest AChE inhibition value (IC50 [μM] 8.40 ± 0.32). In the search for a compound showing combined activities (antioxidant and AChE inhibition), the compound 4, octane-1,8-diyl-bis-S-amidinothiourea dihydrobromide, (19.02 ± 1.52 μM eq Trolox; IC50 [μM] 8.40 ± 0.32) was chosen to carry out a molecular docking study. The results showed that compound 4 has the ability to bind the active site of acetylcholinesterase with considerable affinity (estimated binding energies of -8.5 kcal/mol). All data indicate that compound 4 has the potential to be further investigated as a possible candidate in the Alzheimer's disease treatment.

Imaging Findings and Management Strategies for Liver Masses in Children with Predisposition Disorders: A Review by the Pediatric LI-RADS Group.

Liver masses in children with underlying systemic disease or a predisposing syndrome can be benign or malignant, ranging from focal fat to hepatocellular carcinoma (HCC). Knowledge of the underlying condition, the pathophysiologic effect on the liver, and the development of liver disease and specific liver lesions allows radiologists to guide imaging with regard to modality and frequency and give recommendations for biopsy when appropriate. In some predisposition disorders, such as Beckwith Wiedemann spectrum, familial adenomatous polyposis syndrome, and tuberous sclerosis complex, established guidelines for imaging screening exist. In many of the syndromes discussed, masses may occur outside of the liver and the liver may not be the primary focus of screening. For other entities, no consensus recommendations exist. Screening recommendations may be based on the risk of development of chronic liver disease. Once cirrhosis occurs, the risk of developing HCC is elevated. The authors summarize the spectrum of liver lesions that may be encountered in children with predisposing syndromes and systemic diseases, the imaging appearance of the lesions with various modalities, and screening guidelines where published. ©RSNA, 2024 See the invited commentary by Rutten and Chavan in this issue.

Pathophysiological Effects on Coronary Arteries Following Radiofrequency Ablation: A Comprehensive Review.

Radiofrequency ablation (RFA) is a safe and effective treatment for patients experiencing ventricular and atrial tachyarrhythmias. While complications after RFA are generally rare, the occurrence of coronary artery (CA) injury, albeit infrequent, can have significant clinical implications. Given the proximity of CAs to common ablation sites, understanding the interplay between RFA and CA perfusion pathophysiology is paramount. Although previous studies have discussed the presentation and outcomes of CA injury post-ablation, a comprehensive review consolidating the mechanisms of CA injury following RFA remains absent in the cardiology literature. In this review, we conducted an extensive literature search spanning the past three decades to explore the link between the biophysics of RFA and CA perfusion pathophysiology, focusing on injury mechanisms. We delve into RFA lesion pathology, elucidate the mechanisms of CA injury resulting from RFA, and examine factors influencing lesion formation, such as convective cooling and the "shadow effect." Furthermore, we outline methods to mitigate CA injury post-RFA and propose novel research avenues to optimize lesion formation and ensure the safety of arrhythmia treatments, particularly in cases where tissue ablation is performed close to CAs.

Association between allostatic load and cardiac structural and functional abnormalities in young adults with serious mental disorders.

Allostatic load refers to the pathophysiological consequences of uncompensated adaptation to chronic stress. Few studies have investigated the effect of allostatic load on cardiac health in patients with serious mental disorders (SMDs), a population at high risk of cardiac mortality. Herein we evaluated associations between allostatic load and cardiac structure and function in young adults with SMDs. A total of 106 participants aged younger than 45years underwent echocardiographic study, blood biochemistry examination, and blood cell count analysis. Echocardiographic imaging was conducted in accordance with recommendations of the American Society of Echocardiography and European Association of Cardiovascular Imaging. Allostatic load index was calculated using 15 measures representing cardiovascular, metabolic, and inflammatory or oxidative stress markers. The SMD group exhibited a significantly higher allostatic load index than did control (Cohen's d=0.59). Additionally, they exhibited a greater left ventricular relative wall thickness (LVRWT, Cohen's d=0.39) and a less favorable mitral valve E/A ratio (Cohen's d=0.31), left ventricular ejection fraction (Cohen's d=0.51), and global longitudinal strain (Cohen's d=0.71). After demographic and clinical characteristics were adjusted for, multiple linear regression revealed that allostatic load index was positively associated with LVRWT (β=0.255) and negatively associated with mitral valve E/A ratio (β=-0.247) in the SMD group. This is the first study to suggest that allostatic load may play a critical role in accelerated adverse cardiac remodeling among young patients with SMDs. Future studies should elucidate the underlying mechanisms.

Differential modulation of the hepatocellular metabolome, cytoprotective and inflammatory responses due to endotoxemia and lipotoxicity.

The present work aimed to examine the primary mechanisms of liver damage, namely the impact of gut-derived endotoxins along the gut-liver axis and adipose-derived free fatty acids along the adipose-liver axis. These processes are known to play a significant role in the development of hepatic inflammation and steatosis. Although possible overlapping in the pathogenesis was expected, these processes have unique pathophysiological consequences. Therefore, we used HepG2 cells as a model system to investigate the impact of lipopolysaccharides (LPS) and free fatty acid (FFA; albumin conjugated palmitic acid) on the intracellular metabolome. Although both LPS and FFA triggered the expression of nuclear factor κB (NFκB)-dependent inflammation, only LPS treatment was able to trigger a Toll-like receptor 4 (TLR4) dependent response. The intracellular cytoprotective enzymatic levels (catalase, peroxidase, glutathione) were increased due to FFA but lowered due to LPS. The free-radical neutralizing efficacies of cell-free metabolites of FFA-treated cells were better than those of the LPS-treated ones. The use of untargeted metabolomics allowed for the identification of distinct metabolic pathway enrichments, providing further insights into the differential effects of LPS and FFA on the metabolism of hepatocytes. Collectively, the current study highlights the distinct impacts of endotoxemia and lipotoxicity on the metabolome of hepatocytes, hence offering valuable insights into hepatocellular function.

Dysregulated Long Non-coding RNAs in Myasthenia Gravis- A Mini-Review.

Myasthenia gravis (MG) is an acquired autoimmune disease that is mediated by humoral immunity, supplemented by cellular immunity, along with participation of the complement system. The pathogenesis of MG is complex; although autoimmune dysfunction is clearly implicated, the specific mechanism remains unclear. Long non-coding RNAs (lncRNAs) are a class of non-coding RNA molecules with lengths greater than 200 nucleotides, with increasing evidence of their rich biological functions and high-level structure conservation. LncRNAs can directly interact with proteins and microRNAs to regulate the expression of target genes at the transcription and post-transcription levels. In recent years, emerging studies have suggested that lncRNAs play roles in the differentiation of immune cells, secretion of immune factors, and complement production in the human body. This suggests the involvement of lncRNAs in the occurrence and progression of MG through various mechanisms. In addition, the differentially expressed lncRNAs in peripheral biofluid may be used as a biomarker to diagnose MG and evaluate its prognosis. Moreover, with the development of lncRNA expression regulation technology, it is possible to regulate the differentiation of immune cells and influence the immune response by regulating the expression of lncRNAs, which will provide a potential therapeutic option for MG. Here, we review the research progress on the role of lncRNAs in different pathophysiological events contributing to MG, focusing on specific lncRNAs that may largely contribute to the pathophysiology of MG, which could be used as potential diagnostic biomarkers and therapeutic targets.