Clinical Drugs Research Articles

Application of ensemble learning for predicting GABAA receptor agonists

BackgroundOver the past few decades, agonists binding to the benzodiazepine site of the GABAA receptor have been successfully developed as clinical drugs. Different modulators (agonist, antagonist, and reverse agonist) bound to benzodiazepine sites exhibit different or even opposite pharmacological effects, however, their structures are so similar that it is difficult to distinguish them based solely on molecular skeleton. This study aims to develop classification models for predicting the agonists. Methods306 agonists or non-agonists were collected from literature. Six machine learning algorithms including RF, XGBoost, AdaBoost, GBoost, SVM, and ANN algorithms were employed for model development. Using six descriptors including 1D/2D Descriptors, ECFP4, 2D-Pharmacophore, MACCS, PubChem, and Estate fingerprint to characterize chemical structures. The model interpretability was explored by SHAP method. ResultsThe best model demonstrated an AUC value of 0.905 and an MCC value of 0.808 for the test set. The PubMac-based model (PubMac-GB) achieved best AUC values of 0.935 for test set. The SHAP analysis results emphasized that MaccsFP62, ECFP_624, ECFP_724, and PubchemFP213 were the crucial molecular features. Applicability domain analysis was also performed to determine reliable prediction boundaries for the model. The PubMac-GB model was applied to virtual screening for potential GABAA agonists and the top 100 compounds were given. ConclusionOverall, our ensemble learning-based model (PubMac-GB) achieved comparable performance and would be helpful in effectively identifying agonists of GABAA receptors.

InterDILI: interpretable prediction of drug-induced liver injury through permutation feature importance and attention mechanism

Safety is one of the important factors constraining the distribution of clinical drugs on the market. Drug-induced liver injury (DILI) is the leading cause of safety problems produced by drug side effects. Therefore, the DILI risk of approved drugs and potential drug candidates should be assessed. Currently, in vivo and in vitro methods are used to test DILI risk, but both methods are labor-intensive, time-consuming, and expensive. To overcome these problems, many in silico methods for DILI prediction have been suggested. Previous studies have shown that DILI prediction models can be utilized as prescreening tools, and they achieved a good performance. However, there are still limitations in interpreting the prediction results. Therefore, this study focused on interpreting the model prediction to analyze which features could potentially cause DILI. For this, five publicly available datasets were collected to train and test the model. Then, various machine learning methods were applied using substructure and physicochemical descriptors as inputs and the DILI label as the output. The interpretation of feature importance was analyzed by recognizing the following general-to-specific patterns: (i) identifying general important features of the overall DILI predictions, and (ii) highlighting specific molecular substructures which were highly related to the DILI prediction for each compound. The results indicated that the model not only captured the previously known properties to be related to DILI but also proposed a new DILI potential substructural of physicochemical properties. The models for the DILI prediction achieved an area under the receiver operating characteristic (AUROC) of 0.88–0.97 and an area under the Precision-Recall curve (AUPRC) of 0.81–0.95. From this, we hope the proposed models can help identify the potential DILI risk of drug candidates at an early stage and offer valuable insights for drug development.

Prognosis of colorectal cancer, prognostic index of immunogenic cell death associated genes in response to immunotherapy, and potential therapeutic effects of ferroptosis inducers.

This study leverages bioinformatics and medical big data to integrate datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), providing a comprehensive overview of immunogenic cell death (ICD)-related gene expression in colorectal cancer (CRC). The research aims to elucidate the molecular pathways and gene networks associated with ICD in CRC, with a focus on the therapeutic potential of cell death inducers, including ferroptosis agents, and their implications for precision medicine. We conducted differential expression analysis and utilized advanced bioinformatic techniques to analyze ICD-related gene expression in CRC tissues. Unsupervised consensus clustering was applied to categorize CRC patients into distinct ICD-associated subtypes, followed by an in-depth immune microenvironment analysis and single-cell RNA sequencing to investigate immune responses and cell infiltration patterns. Experimental validation was performed to assess the impact of cell death inducers on ICD gene expression and their interaction with ferroptosis inducers in combination with other clinical drugs. Distinct ICD gene expression profiles were identified in CRC tissues, revealing molecular pathways and intricate gene networks. Unsupervised consensus clustering refined the CRC cohort into unique ICD-associated subtypes, each characterized by distinct clinical and immunological features. Immune microenvironment analysis and single-cell RNA sequencing revealed significant variations in immune responses and cell infiltration patterns across these subtypes. Experimental validation confirmed that cell death inducers directly affect ICD gene expression, highlighting their therapeutic potential. Additionally, combinatorial therapies with ferroptosis inducers and clinical drugs were shown to influence drug sensitivity and resistance in CRC. Our findings underscore the importance of ICD-related genes in CRC prognosis and therapeutic targeting. The study provides actionable insights into the efficacy of cell death-inducing therapies, particularly ferroptosis inducers, and their regulatory mechanisms in CRC. These discoveries support the development of precision medicine strategies targeting ICD genes and offer valuable guidance for translating these therapies into clinical practice, with the potential to enhance CRC treatment outcomes and patient survival.

Drugs and clinical prospects for the treatment of atherosclerosis

Atherosclerosis is a disease that occurs in blood vessels and is also responsible for numerous diseases, including coronary heart disease and cerebral infarction. It can affect the function of many organs of the human body, cause great damage to human health, and the incidence is high in the middle-aged and elderly people. The pathogenesis of atherosclerosis is very complex, which is the result of inflammation caused by lipid deposition on the blood vessel wall. At present, aspirin is the most commonly used drug in clinic. It has strong anti-inflammatory and antithrombotic effects. In addition, high density lipoprotein, or HDL, can transport cholesterol in the blood vessels, and it does exert some influence on the treatment of atherosclerosis, but the exact therapeutic pathway is still the subject of ongoing research. This paper illustrates the pathogenesis of atherosclerosis, and introduces the mechanism and feasibility of two therapeutic modalities, aspirin and HDL, and gives a reasonable future research direction.

Microbial-derived Urolithin A Targets GLS1 to Inhibit Glutaminolysis and Attenuate Cirrhotic Portal Hypertension

Background and AimsCirrhotic portal hypertension (CPH) is the leading cause of mortality in patients with cirrhosis. Over 50% patients with CPH treated with current clinical pharmacotherapy still present variceal bleeding or sometimes death owing to insufficient reduction in portal pressure. Elevated intrahepatic vascular resistance (IHVR) plays a fundamental role in increasing portal pressure. Because of its potent effect in reducing portal pressure and maintaining normal portal inflow to preserve liver function, lowering the IHVR is acknowledged as an optimal anti-CPH strategy but without clinical drugs. We aimed to investigate the protective effect of microbial-derived Urolithin A (UroA) in IHVR and CPH. MethodsCCl4 or BDL surgery was administered to mice to induce liver fibrosis and CPH. 16S rRNA gene sequencing was used for microbial analysis. Transcriptomics and metabolomics analyses were employed to study the host and cell responses. ResultsUroA was remarkably deficient in patients with CPH and was negatively correlated with disease severity. UroA deficiency was also confirmed in CPH mice and was associated with a reduced abundance of UroA-producing bacterial strain (Lactobacillus murinus, L. murinus). Glutaminolysis of hepatic stellate cells (HSCs) was identified as a previously unrecognized target of UroA. UroA inhibited the activity of glutaminase1 to suppress glutaminolysis, which counteracted fibrogenesis and contraction of HSCs and ameliorated CPH by relieving IHVR. Supplementation with UroA or L. murinus effectively ameliorated CPH in mice. ConclusionsWe for the first time identify the deficiency of gut microbial metabolite UroA as an important cause of CPH. We demonstrate that UroA exerts an excellent anti-CPH effect by suppressing HSC glutaminolysis to lower the IHVR, which highlighted its great potential as a novel therapeutic agent for CPH.

Nisin A elevates adenosine to achieve anti-inflammatory activity.

Inflammation is a ubiquitous physiological status that exists during the occurrence, development and prognosis of numerous diseases. Clinical anti-inflammatory drugs mainly include antibiotics, antivirals, non-steroids and corticosteroids, and the treatments are often accompanied by side effects, including nausea, abdominal pain, allergy, nerve injury and organ dysfunction. Current studies have focused on continuously exploring efficient anti-inflammatory natural components with high biosafety, while nisin, a natural bioactive anti-microbial peptide produced by Lactococcus, has been reported to have anti-inflammatory activity via its superior anti-bacterial abilities. Several recent studies have focused on the potent direct anti-inflammation of nisin, whereas its effects and the corresponding mechanism still remain unclear. The cellular and Caenorhabditis elegans (C. elegans) models were constructed in this study to evaluate the anti-inflammatory effects of nisin A both in vitro and in vivo, while the inflammatory mechanism was further uncovered based on omics analysis. This study reveals the direct anti-inflammatory activity of nisin A and elucidates the regulatory actions of nisin A on adenosine, followed by alteration of the sphingolipid signaling pathway and purine metabolism, enhancing the deep understanding of nisin A with its anti-inflammatory capacity, providing new ideas for future nisin A-based anti-inflammatory strategies.

A potential biomarker of disease activity in systemic lupus erythematosus, systemic immune-inflammation index.

Biomarkers using routine laboratory tests accurately presenting systemic lupus erythematosus (SLE) disease activity may have important practical values in clinical settings. The primary purpose of this study was to investigate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII; neutrophil X platelet/lymphocyte) as potential biomarkers of disease activity in cases with SLE. In this case-control observational study, cases with SLE and demographically similar healthy controls were included. For clinical evaluation demographic features, disease duration and drugs were recorded. SLE clinical disease activity was assessed with SLEDAI scores. For laboratory assessments; erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and C3-C4 levels and anti-dsDNA positivity were recorded. Based on the simultaneous complete blood count (CBC) of the participants NLR, PLR and SII were calculated. The correlation between clinical and laboratory data was analyzed. 68 cases with SLE (64 women, 8 men) and 69 controls (65 women, 4 men) were included in this investigation. The demographic features of the cases and controls were similar. ESR, CRP, NLR, PLR and SII scores were statistically higher in cases with SLE than controls (p<0.000). Statistically significant positive correlations between SLEDAI and NLR, PLR and SII scores were demonstrated (p=0.01, r=0.505; 0.414; 0.698, respectively). We determined a cut-off value of SII as 681,3 presenting 77% sensitivity and 76% specificity to discriminate no-mild disease activity and moderate-higher SLE disease activity status. The SII cut-off value was determined as 681,3 presenting 77% sensitivity and 76% specificity (p<0.000, and AUC=0.930). CBC indices were shown to be higher in cases with SLE than healthy controls in our study. By presenting a strong correlation with disease activity and discriminating ability of disease status, SII might serve as a biomarker supporting clinical evaluation in SLE.

Pharmacophore mapping, 3D QSAR, molecular docking, and ADME prediction studies of novel Benzothiazinone derivatives.

In the quest to combat tuberculosis, DprE1, a challenging target for novel anti-tubercular agents due to its small size and membrane location, has been a focus of research. DprE1 catalyzes the transformation of DPR into Ketoribose DPX, with Benzothiazinone emerging as a potent pharmacophore for inhibiting DprE1. Clinical trial drugs such as BTZ043, BTZ038, PBTZ169, and TMC-207 have shown promising results as DprE1 inhibitors. This study employed pharmacophore mapping of Pyrazolopyridine, Dinitrobenzamide, and Benzothiazinone derivatives to identify crucial features for eliciting a biological response. Benzothiazinone (Ligand code: 73) emerged as a reference ligand with a fitness score of 3.000. ROC analysis validated the pharmacophore with an excellent score of 0.71. To build a 3D QSAR model, a series of Benzothiazinone congeneric derivatives were explored. The model exhibited strong performance, with a standard deviation of 0.1531, a correlation coefficient for the training set (R2) value of 0.9754, and a correlation coefficient for test set Q2 value of 0.7632, indicating robust predictive capabilities. Contour maps guided the design of novel benzothiazinone derivatives, emphasizing steric, electrostatic, hydrophobic, H-bond acceptor, and H-bond donor groups for structure-activity relationships. Docking studies against PDB ID: 4NCR demonstrated favorable scores, with interactions aligning well with the in-built ligand 26J. Docking validation via RMSD values supported the reliability of the docking results. This comprehensive approach aids in the design of novel benzothiazinone derivatives with potential anti-tubercular properties, contributing to the development of novel anti-tubercular agents which can be pivotal in the eradication of tuberculosis.

Design, synthesis and evaluation of 2-phenylpyrimidine derivatives as novel antifungal agents targeting CYP51.

Invasive fungal infections, with high morbidity and mortality, have become one of the most serious threats to human health. There are a few kinds of clinical antifungal drugs but large amounts of them are used, so there is an urgent need for a new structural type of antifungal drug. In this study, we carried out three rounds of structural optimisation and modification of the compound YW-01, which was obtained from the preliminary screening of the group, by using the strategy of scaffold hopping. A series of novel phenylpyrimidine CYP51 inhibitors were designed and synthesised. In vitro antifungal testing showed that target compound C6 exhibited good efficacy against seven common clinically susceptible strains, which was significantly superior to the clinical first-line drug fluconazole. Subsequently in vitro tests on metabolic stability and cytotoxicity revealed that C6 was safe and stable for hepatic microsomal function. Finally, C6 warranted further exploration as a possible novel structural type of CYP51 inhibitor.

In silico network pharmacology study on Glycyrrhiza glabra: Analyzing the immune-boosting phytochemical properties of Siddha medicinal plant against COVID-19.

Immunosenescence is a pertinent factor in the mortality rate caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The changes in the immune system are strongly associated with age and provoke the deterioration of the individual's health. Traditional medical practices in ancient India effectively deal with COVID-19 by boosting natural immunity through medicinal plants. The anti-inflammatory and antiviral properties of Glycyrrhiza glabra are potent in fighting against COVID-19 and promote immunity boost against the severity of the infection. Athimadhura Chooranam, a polyherbal formulation containing Glycyrrhiza glabra as the main ingredient, is recommended as an antiviral Siddha herb by the Ministry of AYUSH. This paper is intended to identify the phytoconstituents of Glycyrrhiza glabra that are actively involved in preventing individuals from COVID-19 transmission. The modulated pathways, enrichment study, and drug-likeness are calculated from the target proteins of the phytoconstituents at the pharmacological activity (Pa) of more than 0.7. Liquiritigenin and Isoliquiritin, the natural compounds in Glycyrrhiza glabra, belong to the flavonoid class and exhibit ameliorative effects against COVID-19. The latter compound displays a higher protein interaction to a maximum of six, out of which HMOX1, PLAU, and PGR are top-hub genes. ADMET screening further confirms the significance of the abovementioned components containing better drug-likeness. The molecular docking and molecular dynamics method identified liquiritigenin as a possible lead molecule capable of inhibiting the activity of the major protease protein of SARS-CoV-2. The findings emphasize the importance of in silico network pharmacological assessments in delivering cost-effective, time-bound clinical drugs.

Synthesis of cationic N-acylated thiazolidine for selective activity against Gram-positive bacteria, and evaluation of N-acylation’s role in membrane-disrupting activity

The evolution of antimicrobial-resistant strains jeopardizes the existing clinical drugs and demands new therapeutic interventions. Herein, we report the synthesis of cationic thiazolidine bearing quaternary pyridinium group, in which thiazolidine...

Nanozymes in Alzheimer's disease diagnostics and therapy.

Alzheimer's disease (AD) is a progressive neurodegenerative condition that has become an important public health problem of global concern, and the early diagnosis and etiological treatment of AD are currently the focus of research. In the course of clinical treatment, approved clinical drugs mainly serve to slow down the disease process by relieving patients' clinical symptoms. However, these drugs do not target the cause of the disease, and the lack of specificity of these drugs has led to undesirable side effects in treatment. Meanwhile, AD is mainly diagnosed by clinical symptoms and imaging, which does not have the advantage of early diagnosis. Nanozymes have been extensively investigated for the diagnosis and treatment of AD with high stability and specificity. Therefore, this review summarizes the recent advances in various nanozymes for AD diagnosis and therapy, including with peroxidase-like-activity gold nanozymes, iron nanozymes, superoxide dismutase-like- and catalase-like-activity selenium dioxide nanozymes, platinum nanozymes, and peroxidase-like palladium nanozymes, among others. A comprehensive analysis was conducted on the diagnostic and therapeutic characteristics of nanozyme therapy for AD, as well as the prospects and challenges of its clinical application. Our goal is to advance this emerging topic by building on our own work and the new insights we have learned from others. This review will assist researchers to quickly understand relevant nanozymes' therapeutic and diagnostic information and further advance the field of nanozymes in AD.

Identification of echinoderm metabolites as potential inhibitors targeting wild-type and mutant forms of Escherichia coli RNA polymerase (RpoB) for tuberculosis treatment.

Tuberculosis (TB) remains a critical global health challenge, with the emergence of drug-resistant strains heightening concerns. The development of effective drugs targeting both wild-type (WT) and mutant Escherichia coli RNA polymerase β subunit (RpoB) is crucial for global TB control, aiming to alleviate TB incidence, mortality, and transmission. This study employs molecular docking and ADMET analyses to screen echinoderm metabolites for their potential inhibition of Escherichia coli RNA polymerase, focusing on wild-type and mutant RpoB variants associated with TB drug resistance. The evaluation of docking results using the glide gscore led to the selection of the top 10 compounds for each protein receptor. Notably, CMNPD2176 demonstrated the highest binding affinity against wild-type RpoB, CMNPD13873 against RpoB D516V mutant, CMNPD2177 against RpoB H526Y mutant, and CMNPD11620 against RpoB S531L mutant. ADMET screening confirmed the therapeutic potential of these selected compounds. Additionally, MM-GBSA binding free energy calculations and molecular dynamics simulations provided further support for the docking investigations. While the results suggest these compounds could be viable for tuberculosis treatment, it is crucial to note that further in-vitro research is essential for the transition from prospective inhibitors to clinical drugs.

Anti-hyperuricemia bioactive peptides: a review on obtaining, activity, and mechanism of action.

Hyperuricemia, a disorder of uric acid metabolism, serves as a significant risk factor for conditions such as hypertension, diabetes mellitus, renal failure, and various metabolic syndromes. The main contributors to hyperuricemia include overproduction of uric acid in the liver or impaired excretion in the kidneys. Despite traditional clinical drugs being employed for its treatment, significant health concerns persist. Recently, there has been growing interest in utilizing protein peptides sourced from diverse food origins to mitigate hyperuricemia. This article provides a comprehensive review of bioactive peptides with anti-hyperuricemia properties derived from animals, plants, and their products. We specifically outline the methods for preparing these peptides from food proteins and elucidate their efficacy and mechanisms in combating hyperuricemia, supported by in vitro and in vivo evidence. Uric acid-lowering peptides offer promising prospects due to their safer profile, enhanced efficacy, and improved bioavailability. Therefore, this review underscores significant advancements and contributions in identifying peptides capable of metabolizing purine and/or uric acid, thereby alleviating hyperuricemia. Moreover, it offers a theoretical foundation for the development of functional foods incorporating uric acid-lowering peptides.

Advances in pathogenesis and treatment of vascular endothelial injury-related diseases mediated by mitochondrial abnormality.

Vascular endothelial cells, serving as a barrier between blood and the arterial wall, play a crucial role in the early stages of the development of atherosclerosis, cardiovascular diseases (CVDs), and Alzheimer's disease (AD). Mitochondria, known as the powerhouses of the cell, are not only involved in energy production but also regulate key biological processes in vascular endothelial cells, including redox signaling, cellular aging, calcium homeostasis, angiogenesis, apoptosis, and inflammatory responses. The mitochondrial quality control (MQC) system is essential for maintaining mitochondrial homeostasis. Current research indicates that mitochondrial dysfunction is a significant driver of endothelial injury and CVDs. This article provides a comprehensive overview of the causes of endothelial injury in CVDs, ischemic stroke in cerebrovascular diseases, and AD, elucidating the roles and mechanisms of mitochondria in these conditions, and aims to develop more effective therapeutic strategies. Additionally, the article offers treatment strategies for cardiovascular and cerebrovascular diseases, including the use of clinical drugs, antioxidants, stem cell therapy, and specific polyphenols, providing new insights and methods for the clinical diagnosis and treatment of related vascular injuries to improve patient prognosis and quality of life. Future research should delve deeper into the molecular and mechanistic links between mitochondrial abnormalities and endothelial injury, and explore how to regulate mitochondrial function to prevent and treat CVDs.

Site-specific thrombus formation: advancements in photothrombosis-on-a-chip technology.

Thrombosis, characterized by blood clot formation within vessels, poses a significant medical challenge. Despite extensive research, the development of effective thrombosis therapies is hindered by substantial costs, lengthy development times, and high failure rates in medication commercialization. Conventional pre-clinical models often oversimplify cardiovascular disease, leading to a disparity between experimental results and human physiological responses. In response, we have engineered a photothrombosis-on-a-chip system. This microfluidic model integrates human endothelium, human whole blood, and blood flow dynamics and employs the photothrombotic method. It enables precise, site-specific thrombus induction through controlled laser irradiation, effectively mimicking both normal and thrombotic physiological conditions on a single chip. Additionally, the system allows for the fine-tuning of thrombus occlusion levels via laser parameter adjustments, offering a flexible thrombus model with varying degrees of obstruction. Additionally, the formation and progression of thrombosis noted on the chip closely resemble the thrombotic conditions observed in mice in previous studies. In the experiments, we perfused recalcified whole blood with Rose Bengal into an endothelialized microchannel and initiated photothrombosis using green laser irradiation. Various imaging methods verified the model's ability to precisely control thrombus formation and occlusion levels. The effectiveness of clinical drugs, including heparin and rt-PA, was assessed, confirming the chip's potential in drug screening applications. In summary, the photothrombosis-on-a-chip system significantly advances human thrombosis modeling. Its precise control over thrombus formation, flexibility in the thrombus severity levels, and capability to simulate dual physiological states on a single platform make it an invaluable tool for targeted drug testing, furthering the development of organ-on-a-chip drug screening techniques.

Research progress on the targets and therapies of Alzheimer’s disease

Alzheimer 's disease (AD) is a progressive neurodegenerative disease. Most of the patients have the following characteristics, such as abnormalities in memory, language, and behavioral ability. It is very common in dementia in the elderly. The pathological features are mainly the plaques formed by Aβ protein deposition and the neurofibrillary tangles. The causes of AD are complex, and there are many pathological hypotheses. The current clinical therapeutic drugs for AD are mainly cholinesterase inhibitors developed based on the cholinergic hypothesis and receptor antagonists targeting NMDA receptors. Although there are some research results on the targets based on other hypotheses, further research is needed for clinical application. Nevertheless, in recent years, there have been many new development directions, such as combination therapy. Multi-target combination therapy is expected to achieve better efficacy than traditional single-target therapy. This makes it even more important to develop drugs with different potential targets. This article introduces three current mainstream therapeutic targets and theories, and introduces the drugs based on them. At the same time, we also introduced 3 targets and therapies with good potential in the future, and introduced some current stage results and current drugs based on their research and development.

Study on the inhibitory effect of fermentation extract of Microporus vernicipes on Candida albicans.

Candida albicans is one of the most common species of Candida, which cause various mucosal and systemic infectious diseases. However, the resistance rate to existing clinical antifungal drugs gradually increases in C. albicans. Therefore, new antifungal drugs must be developed to solve the current problem. This study discovered that the solid fermented ethyl acetate crude extract of Microporus vernicipes had inhibitory activity on C. albicans. This study determined that the Mv5 components had significantly inhibited the activity of C. albicansusing column chromatography separation component screening. The components included 23 compounds of fatty acids and their derivatives, alkaloids, phenols, and other classes using ultra-high performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HR-MS) analysis, with fatty acids constituting the primary components. The mechanism of action showed that the minimum inhibitory concentration (MIC) of Mv5 components against C. albicans was 15.63μg/mL, while minimum fungicidal concentration (MFC) was 31.25μg/mL. Mv5 components can inhibit the early biofilm formation and destroy the mature biofilm structure. It can inhibit the germ tube growth of C. albicans, thereby inhibiting the transformation of yeast morphology to hyphae. We detected 193 differentially expressed genes, including 156 upregulated and 37 downregulated genes in the Mv5 components of the MIC concentration group. We detected 391 differentially expressed genes, including 334 upregulated and 57 downregulated expression genes in the MFC concentration group. Among these differentially expressed genes, the genes related to mycelium and biofilm formation were significantly downregulated. GO enrichment analysis presented that single-organism process metabolic process, and cellular processes were the biological processes with the most gene enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG)of Mv5 components were mainly enriched in metabolic pathways, such as meiosis yeast and amino acid metabolism. Therefore, it is believed that the fermentation extract of M. vernicipes inhibits C. albicans, which can provide clues for developing effective antifungal drugs.

Active components of Solanum nigrum and their antitumor effects: a literature review.

Cancer poses a serious threat to human health and overall well-being. Conventional cancer treatments predominantly encompass surgical procedures and radiotherapy. Nevertheless, the substantial side effects and the emergence of drug resistance in patients significantly diminish their quality of life and overall prognosis. There is an acute need for innovative, efficient therapeutic agents to address these challenges. Plant-based herbal medicines and their derived compounds offer promising potential for cancer research and treatment due to their numerous advantages. Solanum nigrum (S. nigrum), a traditional Chinese medicine, finds extensive use in clinical settings. The steroidal compounds within S. nigrum, particularly steroidal alkaloids, exhibit robust antitumor properties either independently or when combined with other drugs. Many researchers have delved into unraveling the antitumor mechanisms of the active components present in S. nigrum, yielding notable progress. This literature review provides a comprehensive analysis of the research advancements concerning the active constituents of S. nigrum. Furthermore, it outlines the action mechanisms of select monomeric anticancer ingredients. Overall, the insights derived from this review offer a new perspective on the development of clinical anticancer drugs.

Apoferritin-Cu(II) Nanoparticles Induce Oncosis in Multidrug-Resistant Colon Cancer Cells.

Multidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non-apoptosis-inducing agents that circumvent drug resistance. Herein, four therapeutic copper complexes encapsulated in natural nanocarrier apoferritin (AFt-Cu1-4) are reported. Although they are isomers, they exhibit significantly different organelle distributions and cell death mechanisms. AFt-Cu1 and AFt-Cu3 accumulate in the cytoplasm and induce autophagy, whereas AFt-Cu2 and AFt-Cu4 can quickly enter the nucleus and trigger oncosis. Excitedly, AFt-Cu2 and AFt-Cu4 show a strong tumor growth inhibition effect in mice models bearing multidrug-resistant colon xenograft via intravenous injection. To the best of the authors' knowledge, this is the first example of metal-based nucleus-targeted oncosis inducers overcoming multidrug resistance in vivo.