Pathogenic Mechanisms Research Articles

Ultra-High-Performance Liquid Chromatography-Orbitrap-MS-Based Untargeted Lipidomics Reveal Lipid Characteristics of a Clinical Strain of Mycoplasma bovis from Holstein Cow.

Mycoplasma bovis is a global concern for the cattle industry owing to its high rates of infection and resulting morbidity, but there are no reports on the lipid composition and metabolic pathways. This study examined the lipidomics of M. bovis to better investigate the biological characteristics of clinical isolates of M. bovis. The M. bovis strains NX114 and PG45, cultivated to log-phase, underwent untargeted lipidomics via ultra-high-performance liquid chromatography-mass spectrometry for differential analysis. Over 65 lipid types and 1476 lipid molecules were identified. We found that glycerophospholipids and sphingolipids constitute the predominant lipid components of M. bovis, with significant constituents of its cell membrane comprising ceramides, phosphatidylglycerols, sphingomyelins, triacylglycerols, hexosylceramides, ether-linked oxidized phosphatidylcholines, and oxidized phosphatidylglycerols. Secondly, 562 differentially expressed lipid molecules were identified, including 17 lipid subclasses (15 up-regulated and 2 down-regulated) with significant differences in relative content. These findings indicate that distinct M. bovis isolates contain structurally varied lipid molecules, with sphingomyelin, phosphatidylinositol, cardiolipin, and phosphatidylcholine being characteristic lipids. The glycerophospholipid metabolism pathway was identified as a key pathway regulating lipid metabolism in M. bovis by KEGG pathway enrichment analysis. The results indicated alterations in the lipid metabolism of M. bovis, offering insights into its pathogenic mechanisms.

Transcriptomic analysis reveals pathogenicity mechanisms of Phytophthora capsici in black pepper.

The devastating disease "quick wilt" or "foot rot" is caused by the oomycete Phytophthora capsici Leonian and is affecting the economically significant spice crop black pepper (Piper nigrum L.). The details on the mechanism of interaction of P. capsici with its host black pepper remain poorly understood, hindering efforts to enhance disease resistance. To address this knowledge gap, we conducted an RNA-seq analysis to investigate the gene expression profile of P. capsici infecting black pepper. Comparative transcriptome analysis between axenic culture, and early and late infection stages of P. capsici revealed a substantial number of differentially expressed genes. Our findings demonstrate the induction of metabolic pathways, signaling cascades, and crucial pathogenicity-related processes during infection of black pepper by P. capsici. Specifically, we observed orchestrated expression of cell wall-degrading enzymes, effectors, and, detoxifying transporters at different infection time points, implicating their roles in pathogenicity. The expression patterns of key pathogenicity-associated genes, including effectors, were validated using reverse transcription quantitative real-time PCR. The effectiveness of agroinfiltration-mediated transient expression in black pepper for functional studies of effectors is also demonstrated in this study. Overall, this study establishes a strong foundation for further studies elucidating the pathogenic mechanisms employed by P. capsici infecting black pepper and for developing effective disease management strategies. Future investigations building upon these findings are essential for advancing our understanding of this pathosystem and for implementing targeted approaches to mitigate black pepper foot rot.

Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke.

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO's aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe-TMAO pathway.

Effects of the Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Empagliflozin Added to Metformin in Patients with Type 2 Diabetes

Introduction: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by a progressive decline in pancreatic beta-cell function and insulin resistance. Multiple blood glucose-lowering agents targeting the main pathogenic mechanisms of insulin deficiency and insulin resistance are available for the management of type 2 diabetes. However, many patients do not achieve or maintain recommended blood glucose targets even with combination therapies, which are often delayed. Therefore, this study aimed to observe the effects of Empagliflozin as an add-on to Metformin in patients with type 2 diabetes. Methods: This was a retrospective observational study and was conducted in the Department of Medicine, Popular Medical College Hospital, Dhaka, Bangladesh during the period from January 2023 to December 2023. In our study, we included 255 type 2 diabetes mellitus patients who came to receive treatment at the outdoor department of medicine of our hospital. The patients were divided into three groups- Group A (Patients who received the combination of Empagliflozin 10 mg and Metformin 1000 mg), Group B (Patients who received Empagliflozin 10 mg), and Group C (Patients who received Metformin 1000 mg). Result: We found the mean age was 55.8 ± 11.3 years. Most of our patients were male (60%). Among our patients, the majority (57.25%) of them had HbA1c of 8% to 9%. Most patients (60%) got < 8% HbA1c level in Empagliflozin 10 mg combined with metformin 1000 mg group at the end of our study. The majority (9.41%) of patients in the Empagliflozin 10 mg group had >9% HbA1c level compared to other groups. Dizziness, dyspepsia, diarrhea, nasopharyngitis, hyperglycemia, and hypoglycemia were the most common adverse events. Conclusion: The findings of the study showed that in people with Type 2 diabetes and insufficient glycaemic control, 52 weeks’ treatment with empagliflozin 10 mg as an add-on to metformin 1000 mg resulted in sustained and clinically substantial decreases in HbA1c, body weight,FPG, systolic and diastolic blood pressure.

Characterization of N6-methyladenosine long non-coding RNAs in sporadic congenital cataract and age-related cataract.

To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC). Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs. Large amount of m6A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair. Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Current Treatment Options for Diabetes: A Review

Diabetes mellitus, a chronic condition characterized by insufficient insulin production or utilization, has a rich historical context and has evolved significantly since its early identification in ancient civilizations. This article explores the multifaceted nature of diabetes, including its types—Type 1 diabetes (T1D), Type 2 diabetes (T2D), and Latent Autoimmune Diabetes in Adults (LADA)—alongside the pathogenic mechanisms that contribute to its development. The prevalence of diabetes has escalated globally, posing a substantial healthcare burden and leading to serious complications, including cardiovascular diseases and kidney failure. Management strategies have advanced, highlighting the importance of lifestyle modifications, continuous glucose monitoring, and emerging treatments such as artificial pancreas systems, smart insulin, and gene therapy. Furthermore, the potential of stem cell therapy and nanotechnology in the management of diabetes is discussed, indicating a shift towards innovative therapeutic approaches. This comprehensive overview underscores the necessity of tailored treatment strategies and the ongoing research efforts aimed at improving the quality of life for individuals affected by diabetes while addressing the global diabetes epidemic.

Resolution of Chronic Inflammation, Restoration of Epigenetic Disturbances and Correction of Dysbiosis as an Adjunctive Approach to the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with multifactorial and unclear pathogenesis. Its development is characterized by two key elements: epigenetic dysregulation of molecular pathways involved in AD pathogenesis and disrupted skin and gut microbiota (dysbiosis) that jointly trigger and maintain chronic inflammation, a core AD characteristic. Current data suggest that failed inflammation resolution is the main pathogenic mechanism underlying AD development. Inflammation resolution is provided by specialized pro-resolving mediators (SPMs) derived from dietary polyunsaturated fatty acids acting through cognate receptors. SPM levels are reduced in AD patients. Administration of SPMs or their stable, small-molecule mimetics and receptor agonists, as well as supplementation with probiotics/prebiotics, demonstrate beneficial effects in AD animal models. Epidrugs, compounds capable of restoring disrupted epigenetic mechanisms associated with the disease, improve impaired skin barrier function in AD models. Based on these findings, we propose a novel, multilevel AD treatment strategy aimed at resolving chronic inflammation by application of SPM mimetics and receptor agonists, probiotics/prebiotics, and epi-drugs. This approach can be used in conjunction with current AD therapy, resulting in AD alleviation.

Exploring the Molecular Interaction Between NR2E3 and NR1D1 in Retinitis Pigmentosa: A Docking and Molecular Dynamics Study

ABSTRACTBackground and AimsRetinitis pigmentosa (RP) is a hereditary retinal disorder that gradually leads to vision loss due to photoreceptor cell degeneration. This study aims to investigate the clinical features and genetic underpinnings of RP within a large Iranian family. Our focus centered on mutations in the NR2E3 gene, which plays a critical role in the development and maintenance of the retina.MethodsTwenty‐five family members showed symptoms of RP, and fourteen of them underwent clinical examinations conducted by geneticists and ophthalmologists. The DNA samples of five individuals diagnosed with RP from the family were subjected to whole‐exome sequencing (WES) as part of the study. The candidate variant identified through WES was subsequently confirmed using bidirectional sequencing in additional family members. Additionally, in silico analysis, including molecular modeling, protein–protein docking, and molecular dynamics simulation (MD), was employed to assess potential pathogenic effects associated with the candidate variants.ResultsOphthalmic examination revealed night blindness, which is a common symptom among affected individuals. Genetic analysis identified a homozygous missense variant (c.934G>A/p.R311Q) in NR2E3 exon 6, which co‐segregates with other affected family members. Furthermore, molecular docking analysis indicated potential disruption in the binding affinity between NR2E3 and NR1D1 proteins. In‐depth, molecular dynamics analysis, considering parameters such as RMSD, RMSF, and hydrogen bonding, revealed notable differences between normal and mutant protein complexes.ConclusionExploring the molecular interaction between NR2E3 and NR1D1 provides new insights into the pathogenic mechanism of the p.R311Q mutation in RP.

Comparison of efficacy of romosozumab with denosumab and risedronate in patients newly initiating glucocorticoid therapy

Abstract Context Wnt/β-catenin signaling pathway is one of the pathogenic mechanisms of glucocorticoid-induced osteoporosis (GIOP). We previously reported the potential of inhibiting sclerostin as a treatment for GIOP. Objective To compare the efficacy of romosozumab (ROMO), a monoclonal antibody against sclerostin, with existing therapy for GIOP. Methods Patients with rheumatic diseases who had not previously received treatment for osteoporosis and were newly treated with prednisolone 15 mg/day or more were randomly assigned to receive ROMO, denosumab (DMAb), or bisphosphonates (BP). After the initiation of GC therapy, we measured the bone mineral density (BMD) of the lumbar spine, femoral neck, and total hip every 6 months and bone turnover markers every 3 months for 12 months. Results Eleven patients were assigned to the ROMO group, 14 to the DMAb group, and 14 to the BP group. The median [25th to 75th percentile] percent change in lumbar spine BMD from baseline at 12 months was the greatest in the ROMO group (ROMO; 8.6 [3.1–12.4] %, DMAb; 3.3 [1.5–6.2] %, BP; -0.4 [-3.4–1.1] %). Among bone formation markers, serum levels of bone alkaline phosphatase were slightly elevated in the ROMO group, while those of N-terminal propeptide of type I procollagen and osteocalcin decreased in all three groups; however, these changes were smaller in the ROMO group. Serum levels of bone resorption markers and a urine bone quality marker decreased in all groups. Conclusion Treatment with ROMO significantly increased lumbar spine BMD in GC-treated patients, suggesting that ROMO is effective for GIOP.

IPEC-J2 Autophagy Induced by TLR4 and NSP6 Interactions Facilitate Porcine Epidemic Diarrhea Virus Replication.

Autophagy is an important cellular response against intracellular pathogens. However, some viruses have evolved mechanisms to hijack this defensive process to provide favorable conditions for virus replication in host cells. The porcine epidemic diarrhea virus (PEDV) has been shown to alter autophagy pathways; however, it is still unknown through which receptors PEDV induces autophagy in IPEC-J2 cells, whether autophagy facilitates PEDV replication, and which functional domains of PEDV proteins are primarily responsible for inducing autophagy. Here, we found that PEDV infection induces autophagy in host cells via distinct and uncoupled molecular pathways. RNA-seq technology was used to analyze the expression patterns of intracellular genes in PEDV-infected IPEC-J2 cells using transcriptomics. The results demonstrate that PEDV triggers autophagy via the cellular pathogen receptor TLR4 and the AKT-mTOR pathway. As evidenced by autophagosome detection, PEDV infection increases autophagosomes and light chain 3 (LC3)-II as well as downregulated AKT-mTOR phosphorylation. Our study revealed that the binding of the viral protein NSP61-2C (56-151aa) to TLR4 triggers autophagy and inactivates the AKT-mTOR pathway, both of which are critical for facilitating PEDV infection. Through screening and analysis, TLR4 was found to be a key gene involved in PEDV-induced autophagy. The screening of the key functional domains of NSP6 (56-151aa) for their ability to induce autophagy in IPEC-J2 cells provided a basis for the in-depth analysis of the pathogenic mechanism of PEDV infection-induced autophagy and promotion of self-replication and also provided an important target for the study of PEDV antiviral drugs. In conclusion, we elucidated that the PEDV infection of IPEC-J2 cells could induce autophagy and found that PEDV could use autophagy to promote its own replication.

Elevated Cerebrospinal Fluid Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 in Asymptomatic C9orf72 Hexanucleotide Repeat Expansion Carriers.

To identify biochemical changes in individuals at higher risk of developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) via C9orf72 hexanucleotide repeat expansion (HRE) heterozygosity. Cross-sectional observational study of 48 asymptomatic C9orf72 HRE carriers, 39 asymptomatic non-carrier controls, 19 people with sporadic ALS, 10 with C9orf72 ALS, 14 with sporadic FTD, and 10 with C9orf72 FTD. Relative abundance of 30 pre-defined cerebrospinal fluid biomarkers of ALS and FTD were compared in asymptomatic C9orf72 HRE carriers and age-matched non-carrier controls. Differential abundance of these proteins was quantified using data independent acquisition mass spectrometry or electro chemiluminescent assay for neurofilament light chain. Unbiased analysis of the entire cerebrospinal fluid proteome was then carried out. Ubiquitin carboxyl-hydrolase isozyme L1 levels were higher in asymptomatic C9orf72 HRE carriers compared with age-matched non-carriers (log2fold change 0.20, FDR-adjusted p-value = 0.034), whereas neurofilament light chain levels did not significantly differ. Ubiquitin carboxyl-hydrolase isozyme L1 levels remained elevated after matching of groups by neurofilament levels (p = 0.011), and after adjusting for age, sex, and neurofilament levels. A significant difference was also observed when restricting analysis to younger participants (<37) matched by neurofilament level (p = 0.007). Elevated cerebrospinal fluid ubiquitin carboxyl-hydrolase isozyme L1 levels in C9orf72 HRE carriers can occur in the absence of increased neurofilament levels, potentially reflecting either compensatory or pathogenic mechanisms preceding rapid neuronal loss. This brings forward the window on changes associated with the C9orf72 HRE carrier state, with potential to inform understanding of penetrance and approaches to prevention. ANN NEUROL 2024.

Exfoliation syndrome genetics in the era of post-GWAS

Exfoliation syndrome (XFS), or pseudoexfoliation syndrome, is considered a systemic disorder that leads to glaucoma with progressive visual field loss. A better insight into the underlying pathogenic mechanism will help diagnose the disease and prevent and slow progression. Here, we provide an overview of disease pathogenesis in the light of GWAS and multi-omics research. We discuss possible environmental interactions related to XFS. We investigate the potential interactions in differentially expressed genes from RNA-Seq by using Ingenuity Pathway Analysis. MAPK pathway was identified as the top network of these genes. Further investigation is needed to verify our results in vivo. It is necessary to establish an animal model mimicking exfoliation syndrome phenotypes.

Analysis and comparison of biomarkers for Alzheimer's disease

Abstract. Alzheimer's disease (AD), commonly known as dementia, is a neurodegenerative disease that causes memory and cognitive decline. Alzheimer's disease is a neurodegenerative disease that causes memory and cognitive deterioration in patients. 70% of the world's more than 50 million elderly patients suffer from Alzheimer's disease. Currently, scholars around the world mainly classify Alzheimer's disease (AD) patients into seven stages from onset to death. The pathogenesis of Alzheimer's disease (AD) has not yet been clarified by studies on different stages, and the main theories include the A- amyloid hypothesis and other theories such as abnormal phosphorylation of Tau protein. The A- amyloid hypothesis proposes that a type of A42 forms a large number of oligomers in the patient's brain due to misfolding and accumulation, which then develop into mature fibres and protofibrils, eventually accumulating into plaques that impede signalling between the patient's nerves and neurons to cause problems in the brain. The Tau protein theory proposes that it is due to over phosphorylation of pTau protein that disrupts the neuronal skeleton and forms neuronal fibre tangles (NFTS) causing impaired axonal transport to affect signalling. fibre tangles (NFTS) causing impaired axonal transport to affect signalling. This review provides an overview of the A amyloid hypothesis and the abnormal phosphorylation of Tau protein hypothesis, and compares their pathogenic mechanisms and proposes ideas to address the different mechanisms. This thesis finds that Alzheimer's disease (AD) can be treated using targeted approaches for different pathogenic mechanisms.

Targeted treatment of gastric cancer and its pathogenic mechanism

Abstract. Gastric cancer (GC) is a malignant tumor with high morbidity and mortality in our country. The traditional treatment methods include operation, radiotherapy and chemotherapy. At present, it cannot be cured by traditional treatment. Targeted therapy is a treatment method for GC targeting specific targets. Currently, the main therapeutic targets developed include HER2, VEGF and EGFR. It has the advantages of less side effects and good efficacy, but it still has the defect of not fully covering the patient population. This paper mainly introduces targeted therapy of GC, an emerging treatment method, and obtains relevant information about the pathogenic mechanism and main drugs of its main targets HER2, VEGF and EGFR. By summarizing the above information, this paper hopes to provide reference for the future research of targeted therapy of GC and make contributions to the development of more new targets of GC in the future.

Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy.

Diabetic retinopathy (DR), as one of the most common and significant microvascular complications of diabetes mellitus (DM), continues to elude effective targeted treatment for vision loss despite ongoing enrichment of the understanding of its pathogenic mechanisms from perspectives such as inflammation and oxidative stress. Recent studies have indicated that characteristic neuroglial degeneration induced by DM occurs before the onset of apparent microvascular lesions. In order to comprehensively grasp the early-stage pathological changes of DR, the retinal neurovascular unit (NVU) will become a crucial focal point for future research into the occurrence and progression of DR. Based on existing evidence, ferroptosis, a form of cell death regulated by processes like ferritinophagy and chaperone-mediated autophagy, mediates apoptosis in retinal NVU components, including pericytes and ganglion cells. Autophagy-dependent ferroptosis-related factors, including BECN1 and FABP4, may serve as both biomarkers for DR occurrence and development and potentially crucial targets for future effective DR treatments. The aforementioned findings present novel perspectives for comprehending the mechanisms underlying the early-stage pathological alterations in DR and open up innovative avenues for investigating supplementary therapeutic strategies.

The study on the preparation of new drugs targeting the pathogenesis and related influencing factors of Alzheimer's disease

Abstract. With the development of society, Alzheimers disease has gradually become an important issue in the world health system. However, after a long period of research, the pathogenic factors and mechanisms of Alzheimers disease are still unclear, which has a serious impact on an increasing number of elderly people. So drug research for Alzheimers disease is particularly urgent. This article takes Alzheimers disease as the background, and proposes constructive treatment suggestions and potential targets by studying the impact mechanisms of some substances. The article consists of four parts: Amyloid Precursor Protein, Brain-Gut Axis , the Curcumin, and Glycogen Synthase Kinase 3 Inhibitors. By exploring each mechanism of action, this paper predicts its therapeutic methods and targets in Alzheimers disease. Through analysis, it is believed that in the future, although people may still not be able to completely cure Alzheimers disease, we can better transform it into a chronic disease. Updating the original diagnostic methods for blood and cerebrospinal fluid can improve the cure rate and enable early detection and treatment.

Isolation, characterization, and whole genome sequencing analysis of Aeromonas veronii from Channa argus in China.

Aeromonas veronii has emerged as a significant pathogen that impacts both fish and mammals. Recently, an infectious disease characterized by multiple ulcers on the body surface with a high mortality rate occurred in Channa argus cultured in Jiangsu Province, China. A Gram-negative bacterial strain (Aer12) was isolated from the body surface of the diseased fish and identified as A. veronii by the physiological, biochemical, and 16S rRNA gene analysis. Intra-peritoneal injection of Aer12 into the healthy C. argus resulted in the development of multiple ulcers on the body surface, and the histopathological results showed that muscle tissue rupture was the most severe symptom. Aer12 showed both protease and lipase activities with no β-hemolytic activity. Furthermore, Aer12 contained seven virulence genes (aer, act, alt, fla, ascV, aexT, and ela) and one antibiotic resistance gene (qnrS) identified by the PCR assay. The results of whole genome sequencing revealed that Aer12 had a circular chromosome that measured 4,719,428bp. It comprised 4301 predicted protein-coding sequences (CDS) in addition to 31 rRNA, 124 tRNA, and 49 sRNA genes. Furthermore, a total of 676 virulence genes and 216 antibiotic resistance genes have been predicted. Aer12 was susceptible to 21 antibiotics, including ampicillin and erythromycin. The results of Chinese herbs susceptibility assay showed that Aer12 was highly susceptible to Sanguisorba officinalis, Galla chinensis, and Schisandra chinensis. The results of this study will serve as a reference for future research on the pathogenic mechanism of A. veronii and the prevention and control of bacterial diseases in C. argus farming.

Mechanism of ropinirole in the treatment of amyotrophic lateral sclerosis

Abstract. Amyotrophic lateral sclerosis (ALS) is now still a rare disease that cannot be cured, so patients are in desperate need of medications that can treat the disease. Until now, many researchers have tried to illustrate the pathogenesis of ALS, including misfolded protein aggregation, oxidative stress damage, etc. At the same time, many drugs are in the research phase. However, no consensus has been reached on the pathogenesis of ALS and the drugs on the market can only slow down the process of ALS. This paper firstly investigated researches on the pathogenesis of ALS, and then investigated the possible mechanism of ropinirole, a drug originally used to treat Parkinsons disease (PD) but promising as a treatment for ALS. Meanwhile, the latest clinical trials of ropinirole were reviewed in this paper, suggesting ropinirole could possibly treat ALS through multiple mechanisms including reducing oxidative stress, inducing autophagy, etc. Through investigation, this paper provides theoretical guidance for future studies on the mechanisms of ropinirole in ALS. However, the pathogenic mechanism of ALS and the therapeutic mechanism of ropinirole are not fully understood, especially the pathway of ropinirole in scavenging ROS and regulating the abnormal metabolism of lipids needs further studies.

The mechanism of action of traditional Chinese medicine in the prevention and treatment of influenza

Abstract. Influenza, because of its virus is highly contagious and easy to mutate, has caused many outbreaks around the world. Traditional Chinese medicine (TCM) has been used in China for the prevention and treatment of influenza since ancient times, and now more and more people choose to use TCMs to prevent and treat influenza in their daily life. At present, researchers have also tried to study the mechanism of action of TCMs against influenza virus from multiple angles, but there are still many problems in the existing research that deserve further improvement. This article summarizes the researches on the mechanism of action of various TCMs against influenza virus by researchers at home and abroad in recent years and divides the mechanism of action of TCM against influenza virus, which according to the pathogenic mechanism of influenza virus, into two categories: direct inhibition and indirect inhibition. At the same time, this article found that many TCMs can also reduce the damage caused by viral infections by inhibiting the body's excessive immune response. This article also found that there are still some problems in the current research, such as unclear active ingredients, unclear effective dosage, lack of clinical trials, lack of comparative experiments between Chinese and Western medicines, and lack of research on influenza virus B, etc., which are hoped to be focused on in the future researches.

Analysis of single-cell RNA sequencing in human oocytes with diminished ovarian reserve uncovers mitochondrial dysregulation and translation deficiency

BackgroundDiminished ovarian reserve (DOR) is clinically characterized by a decrease in the number of available ovarian follicles and a decline in the quality of oocytes, accompanied by hormonal changes. Low quality of DOR oocyte leads to impaired embryo development, an increased risk of aneuploid pregnancies and miscarriages. However, the specific pathogenic mechanism remains unclear, posing a significant challenge for assisted reproductive technology.MethodsFor the first time, our study employed single-cell RNA sequencing to reveal the altered transcriptomic landscape of DOR oocytes at GV stage after ovarian stimulation. Differentially expressed genes analysis (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interactions network analysis were performed.ResultsWe found 132 up-regulated genes and 466 down-regulated genes in DOR oocytes, with the down-regulated genes primarily enriched in mitochondrial function and translation. Hub genes, identified through integrated analysis of WGCNA and DEGs, were further validated in DOR and control oocytes using RT-qPCR. By utilizing hub genes and employing transcription factor enrichment tools, it had been predicted that pleomorphic adenoma gene 1 (PLAG1) played a crucial role as a transcriptional regulatory factor in DOR oocytes. Additionally, we conformed the PLAG1-IGF2 axis was dysregulated in DOR oocytes.ConclusionsTranscriptome analysis revealed that DOR oocytes exhibited mitochondrial dysfunction and translational defects, and the PLAG1-IGF2 axis might be a potential contributor for the low quality of DOR oocytes.