Pharmacology
New Phenylpropanoid from Croton velutinus (Euphorbiaceae) as Potential Anticancer Natural Product Targeting MAPKs: Review with Docking Approach
Cancer encompasses a group of diseases characterized by uncontrolled cell growth and the ability to invade or spread to other parts of the body. It is considered a major public health issue being the second leading cause of death worldwide. A crucial signaling pathway altered in many cancers is the Mitogen-Activated Protein Kinase (MAPK) pathway which is associated with the regulation of cell proliferation differentiation and survival playing a central role in the development and maintenance of malignant tumors. Natural products have made significant contributions to pharmacotherapy particularly in the field of cancer treatment. The Euphorbiaceae family comprising approximately 300 genera and over 5000 species is known for its rich diversity of bioactive compounds. Croton velutinus (Euphorbiaceae) a species predominantly found in Northeast Brazil has recently garnered attention due to its novel phenylpropanoids isolated from its roots. Among these (E)-4-(1-epoxy-78-propen) phenylbenzoate (CV2) has demonstrated potential cytotoxic activity against various human tumor cell lines including B16F10 MCF-7 HL60 HCT-116 and HepG2. This review aims to highlight the antitumor activity of phenylpropanoids derived from the Euphorbiaceae family. Furthermore through molecular docking studies we explored the binding efficacy of CV2 with MAPKs (ERK JNK p38) comparing it to 25 other phenylpropanoid compounds reported in the literature revealing promising interactions that could be further investigated for therapeutic applications.
Sugammadex in Perioperative Neuromuscular Management: Current Advances and Best Practices
Neuromuscular blocking agents (NMBAs) are crucial for anesthesia enabling intubation and optimal surgical conditions. Timely reversal of blockade is critical for safe extubation and recovery. While neostigmine a traditional reversal agent is effective for moderate blockade it has limitations in reversing deep blockade and requires anticholinergics to mitigate side effects. Sugammadex a novel agent addresses these limitations by selectively encapsulating aminosteroid NMBAs like rocuronium providing rapid and reliable reversal. It demonstrates significant advantages including faster recovery and reduced postoperative complications especially in high-risk populations such as elderly patients or those with organ dysfunction. However challenges such as high costs and potential adverse effects including hypersensitivity and cardiovascular events restrict its routine use. This review explores sugammadex’s pharmacological features clinical applications and cost-effectiveness offering strategies to optimize its use in complex surgical scenarios while addressing current limitations.
Exploration of Pharmacological Mechanism of Kaempferol in Treating Rheumatoid Arthritis based on Network Pharmacology, Molecular Modelling, and Experimental Validation
The autoimmune inflammatory disease known as rheumatoid arthritis (RA) has a complicated and poorly understood etiology. Fibroblast-like synoviocytes (FLSs) have tumor-like characteristics in RA including aggressive growth and heightened activation that leads to the release of pro-inflammatory factors. These processes are essential for the gradual deterioration of joint tissues. Kaempferol with the chemical formula 357-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one is found in many different types of plants and plant families. The pharmacological effects of this substance have been well-documented. The benefits of this substance encompass protection for the heart and brain as well as fighting inflammation bacteria cancer osteoporosis and allergies. It also has properties that can help with anxiety pain relief and hormonal balance. However its precise function in the management of RA is still unclear.
To investigate the effect of kaempferol on apoptosis in RA FLSs and elucidate the underlying mechanisms.
We used the CCK-8 assay to assess the effects of different kaempferol concentrations on RA FLSs. We also used flow cytometry with Annexin V-FITC/PI staining to analyse cell cycle distribution and quantify apoptotic cells. To verify apoptosis the TUNEL test was employed. Important proteins associated with apoptosis were verified to be expressed using western blotting. Finally network pharmacology analysis was used to identify potential kaempferol targets and their interactions with AKT1 PIK3R1 and HSP90AA1 proteins were studied using molecular docking and molecular dynamics simulations.
Kaempferol treatment significantly increased apoptosis in RA FLSs up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Specifically kaempferol at 100 and 200 μM increased the apoptosis index to 29.77 ± 6.02% and 55.63 ± 11.05% respectively compared to the control. The induction of caspase-9 and caspase-3 cleavage was observed indicating the activation of the mitochondrial pathway. Kaempferol also inhibited the phosphorylation of PI3K and Akt with a significant reduction in their activation. Molecular docking studies demonstrated that kaempferol interacted with AKT1 PIK3R1 and HSP90AA1 proteins with binding energies of -6.51 -4.26 and -6.51 kcal/mol respectively suggesting a strong affinity and potential direct impact on these proteins.
Kaempferol induces apoptosis in RA FLSs by inhibiting phosphorylation of the PI3K/Akt signaling pathway increasing levels of pro-apoptotic proteins and decreasing levels of anti-apoptotic proteins. Thus kaempferol a naturally occurring flavonoid has great promise in the management of RA.
Cytotoxic Effects of Dysphania ambrosioides Extracts on Oral Squamous Cell Carcinoma
Dysphania ambrosioides commonly known as “mastruz” is a medicinal plant traditionally used for its therapeutic properties including antimicrobial and anti-inflammatory effects. Previous studies have also suggested its antitumor potential. However its role in oral squamous cell carcinoma (OSCC) remains unexplored. This study aimed to evaluate the in vitro cytotoxic effects of D. ambrosioides extracts on SCC4 (OSCC) and HaCaT (human keratinocyte) cell lines.
Crude extracts were obtained using different methods including hexanic ethanolic hydroethanolic (7:3) and aqueous extractions all performed ultrasonic-assisted extraction. The extracts were tested at concentrations ranging from 7.81 µg/mL to 1000 µg/mL using 2-fold serial dilutions. Cell viability was assessed after 48 hours of treatment using the MTT assay with DMSO as the control.
The extracts exhibited concentration-dependent cytotoxic effects on both cell lines with HaCaT cells showing greater sensitivity. However the lack of selectivity toward tumor cells over normal cells suggests a broad-spectrum cytotoxic activity without tumor-specific therapeutic targeting.
These findings highlight the need for further fractionation of the extracts and identification of the bioactive compounds responsible for the observed effects. Although the extracts demonstrated significant cytotoxic activity their therapeutic potential should not be limited to cytotoxicity alone. Future studies should explore additional biological activities such as anti-inflammatory or immunomodulatory properties to fully understand the therapeutic applications of D. ambrosioides.
Design, Molecular Docking, In Vitro and In Vivo Evaluation of Dimenhydrinate-Cyclodextrin Complex for Fast-Disintegrating Tablet
This study aimed to formulate and evaluate dimenhydrinate (DMH) as fast-disintegrating tablets (FDTs) complexed with β-cyclodextrin (β-CD) to enhance its solubility dissolution profile and pharmacological performance.
A DMH:β-CD inclusion complex was prepared at a 1:1 molar ratio using the kneading method. Characterization was performed through phase solubility studies FTIR analysis molecular docking and in vitro dissolution testing. FDTs were developed using various superdisintegrants and assessed for quality attributes of a tablet including hardness friability wetting time water absorption ratio and drug content.
Phase solubility and FTIR analyses confirmed the formation of a stable DMH:β-CD complex. Molecular docking indicated a binding affinity of -4.2 kcal/mol between β-CD and diphenhydramine. Among the FDT formulations CP3 containing 9% crospovidone showed the best performance with a disintegration time of 4.3 seconds and the highest drug release rate. In vivo pharmacological tests demonstrated enhanced sedative and antiemetic activities of the optimized FDTs compared to conventional DMH formulations.
The findings suggest that cyclodextrin-based complexation combined with orodispersible tablet technology can significantly enhance DMH's pharmacological efficacy and patient compliance. However additional investigations on long-term stability pharmacokinetics and clinical scalability are warranted.
The DMH:β-CD FDTs developed in this study offer promising improvements in solubility dissolution and therapeutic performance indicating their potential for better clinical outcomes and patient acceptability.
Integrated Network Pharmacology and Molecular Modeling Approach for Potential PTGS2 Inhibitors against Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory condition of the joints and a leading cause of global disability. However the use of current anti-inflammatory treatments is often limited by serious side effects and multi-organ toxicity necessitating the exploration of safer alternatives.
This study aims to investigate the anti-rheumatic potential of natural compounds of Cassia angustifolia as small-molecule inhibitors of PTGS2.
The therapeutic potential of C. angustifolia was evaluated through antioxidant and anti-inflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was used to identify its constituents. ADMET profiling (absorption distribution metabolism excretion and toxicity) network pharmacology and molecular dynamics simulation were employed to uncover the active compounds against PTGS2 for RA treatment.
C. angustifolia extract contained significant phenolic (18.2 ± 0.008 mg GAE/g DW) and flavonoid (27.57 ± 0.03 mg RE/g DW) content. GC-MS yielded 288 compounds of which four passed the toxicity parameters. Protein-protein interaction analysis revealed 10 RA-related targets with PTGS2 emerging as the most prominent one. Molecular docking and simulations revealed that compound-2 [2-Benzo [13] dioxol-5-yl-8-methoxy-3-nitro-2H-chromene] and compound-4 [alpha-hydroxy-N-[2-methoxyphenyl]-benzene propanamide] binds strongly with PTGS2 (-7.7 kcal/mol and -7.9 kcal/mol respectively) predicting its stable interaction.
C. angustifolia compounds present a significant potential as PTGS2 inhibitors warranting further in vitro and in vivo investigations to confirm their therapeutic efficacy against RA.
Steroid Use, Adrenal Suppression, and Emergency Department Visits in COPD Patients: A Cross-Sectional Study
This study aims to investigate the relationship between steroid use adrenal suppression and frequent emergency department (ED) visits in patients with Chronic Obstructive Pulmonary Disease (COPD).
Systemic glucocorticoids are commonly prescribed in the management of COPD exacerbations; however prolonged or repeated steroid use may lead to adrenal suppression. Although the standard steroid regimen for COPD exacerbations is short-term frequent ED visits may result in cumulative steroid exposure raising concerns about adrenal insufficiency and its clinical consequences.
This study investigates the potential association between steroid-induced adrenal suppression and frequent ED visits among COPD patients. It further examines the impact of steroid administration on cortisol and Adrenocorticotropic hormone (ACTH) levels.
This prospective cross-sectional observational study was conducted in a university-based ED. Patients with COPD with dyspnea and who presented to the ED between 06:00-08:00 were included. Demographics previous presentations to the ED medications used hormone levels and other laboratory results were recorded.
Fifty patients (82% were male) included. Sputum symptoms along with incidences of heart failure were higher in patients who received steroids in the ED. Ronchi was higher crackles and pretibial edema were lower in the patients who received steroids in the ED. Among the patients with low cortisol levels the frequency of patients who received steroids in the ED was higher than those who did not.
Primary healthcare clinicians should monitor COPD patients for potential adrenal insufficiency. Careful regulation of steroid dosages during exacerbation treatment and minimizing polypharmacy are essential to mitigate the long-term effects of prolonged steroid use.
A Rare Case of Ischial Tubercle Pressure Sore with Secondary Periperineal Necrotizing Fasciitis
Perineal necrotizing fasciitis or Fournier's gangrene is a rare but rapidly progressing condition characterized by fascial necrosis. It is a severe potentially life-threatening infection requiring prompt diagnosis and standardized treatment to optimize patient outcomes.
A 48-year-old woman with poorly controlled type 2 diabetes developed necrotizing fasciitis of the right perineum secondary to an ischial tuberosity pressure ulcer. She had a prior spinal cord injury resulting in sensory dysfunction in the lower limbs which masked significant pain. Management included surgical debridement open wound care antimicrobial therapy and a free skin graft for wound closure.
Effective treatment of necrotizing fasciitis relies on aggressive debridement and appropriate antimicrobial therapy. This case highlights the importance of early recognition and intervention to improve clinical diagnostic and management strategies.
Prognostic Value and Immune Characterization of Genes Associated with Childhood Acute Leukemia applying Single-Cell RNA Sequencing
Childhood acute lymphoblastic leukemia (cALL) the most common pediatric hematologic malignancy arises primarily from B-cell origin and is strongly associated with immune dysfunction. This article integrated single-cell and bulk transcriptomic data to identify key B-cell subsets and cALL-related molecules as biomarkers.
Single-cell RNA sequencing (scRNA-seq) Data from 2 pre-B high hyperdiploid (HHD) ALL patients and 3 healthy pediatric bone marrow samples (GSE132509) were utilized for cell clustering using the Seurat package. Functional enrichment pseudo-time trajectory and cell-cell communication analyses were performed using clusterProfiler Monocle2 and CellChat R packages respectively. Bulk RNA-seq data of 511 cALL samples in the TARGET-ALL-P2 cohort were used to construct a prognostic model via Cox and LASSO regression. Immune infiltration differences between different risk groups were analyzed using ESTIMATE MCP-counter and CIBERSORT algorithms.
The scRNA-seq analysis identified five cell subpopulations with B cells demonstrating significant enrichment in cALL samples. Notably the C2 subset was associated with cell proliferation. Ligand-receptor analysis revealed key interactions involving B cell C2. Four marker genes (CENPF IGLL1 ANP32E and PSMA2) were identified to build a risk model. Low-risk patients showed better survival while high-risk patients had higher ESTIMATE scores.
This study examined the key role of B cells in cALL constructed a risk model with strong prognostic predictive ability applying multi-omics analysis and primarily explored its potential mechanism in immune regulation.
This study revealed the critical role of B cells in cALL and the prognostic model showed a high prediction accuracy providing a potential target for individualized treatment of cALL.
Esketamine Reduces Lung Injury Caused by Limb Ischemia-Reperfusion by Regulating Oxidative Stress via the TLR4/NF-κB/NLRP3 Pathway
Esketamine has shown promise in mitigating tissue damage caused by ischemia-reperfusion injury making it a potential therapeutic candidate for acute lung injury (ALI) induced by limb ischemia-reperfusion (LIR-ALI).
This study sought to explore the role and mechanism of esketamine in the LIR-ALI rat model.
The effects of esketamine on the LIR-ALI rats model were evaluated through histopathological examination assessment of pulmonary edema measurement of MDA and SOD levels and analysis of inflammatory cytokine levels (IL-1β etc.) in the bronchoalveolar fluid (BALF) and serum. Western blot analysis was used to assess the expressions of TLR4 NF-κB and NLRP3. TLR4 agonist LPS was used to validate the role of NF-κB/NLRP3 pathway in LIR-ALI.
Esketamine significantly alleviated LIR-induced ALI by reducing pulmonary edema inflammatory cell infiltration and oxidative stress. Elevated MDA content and suppressed SOD activity were significantly reversed by esketamine along with inactivity of the TLR4/NF-κB/NLRP3 pathway. Esketamine treatment reduced inflammatory response in BALF and serum. TLR4 activation by LPS reversed the ameliorative effects of esketamine on LIR-ALI.
Esketamine protected against LIR-induced ALI by mitigating oxidative stress and suppressing the TLR4/NF-κB/NLRP3 axis. These findings highlight the potential therapeutic value of esketamine for ALI.
Single-cell RNA Sequencing Analysis Reveals the Regulatory Functions of Copines Family Genes in Testicular Cancer Progression
The aim of this study is to investigate the expression patterns and regulatory functions of Copines family genes in different cellular subpopulations in testicular cancer based on single-cell data and to analyze the regulatory mechanism of Copines family genes in cancer.
Testicular cancer is a frequently diagnosed male tumor. Emerging evidence suggests that Copines family genes are implicated in a variety of cancer phenotypes and cancer progression. Analyzing the expression pattern of Copines family genes in testicular cancer may help improve the treatment efficacy of the cancer.
This study sought to characterize the expression profiles of Copines family genes in the cellular subpopulations of testicular cancer and to identify key signaling pathways through which they regulate cancer progression.
Based on single-cell transcriptomic data of testicular cancer we classified testicular cancer cell subpopulations and analyzed the expressions of Copines family genes in each subpopulation. Cell subpopulations were grouped according to the expression levels of Copines family genes and differentially expressed Copines family genes between the groups were screened by differential expression analysis. Functional enrichment analysis on the differentially expressed genes (DEGs) was performed with a clusterprofiler package. Functional pathways enriched by the Copines family genes were calculated by AUCell enrichment score. Copy number variation (CNV) analysis was performed using inferCNV to analyze gene mutation patterns across cellular subpopulations and pseudotime analysis was conducted using Monocle to infer cellular differentiation pathways of cellular subpopulations.
Single-cell clustering identified four major cell subpopulations namely NK/T cells tumor cells B cells and macrophages. Notably the control samples had a relatively small proportion of tumor cells. Further clustering of the tumor cells identified six cell subpopulations among which multiple Copines genes especially CPNE1 and CPNE3 showed a high expression. The testicular cancer samples were grouped by the expression patterns of Copines genes and the DEGs between groups included GNLY MGP1 CFD2 CCL21 SPARCL13 as well as some other genes involved in the malignant progression of cancer. Pseudotime analysis showed that the upregulated genes were enriched in cell migration and PI3K-Akt pathway while the downregulated genes were related to immunity. This indicated that the Copines genes regulated the cellular heterogeneity and malignant transformation in testicular cancer.
This study revealed the potential molecular mechanism through which Copines family genes drove the progression of testicular cancer through regulating PI3K-Akt signaling pathway and cell cycle providing a new target for the development of precision treatment targeting Copines family genes and prognostic assessment of the cancer.
Sterile Inflammation and Cell Death Pathways in Liver Ischemia-Reperfusion Injury: A Review and Perspective
Hepatic Ischemia-Reperfusion Injury (IRI) is a critical complication in liver transplantation and resection driven by oxidative stress and sterile inflammation mediated by damage-associated molecular patterns (DAMPs). Current therapeutic challenges arise from interconnected cell death pathways and redundant inflammatory mechanisms.
This review synthesizes mechanistic insights into DAMP signaling and regulated cell death modalities in IRI aiming to identify translational gaps and propose precision-targeted therapies.
A literature search in PubMed using keywords “IRI” “DAMPs” and cell death modes was conducted without date restrictions. Peer-reviewed studies on human/animal models were included with qualitative synthesis of DAMP-cell death interactions.
During ischemia mitochondrial dysfunction releases HMGB1 ATP and mtDNA activating Kupffer cell TLR4/RAGE and cGAS-STING pathways triggering NLRP3 inflammasome- driven cytokine storms. Reperfusion amplifies ROS bursts lipid peroxidation and iron overload creating a self-sustaining cycle of damage. Cell death modalities exhibit spatiotemporal specificity: hepatocyte ferroptosis dominates early injury while macrophage pyroptosis and necroptosis predominate in steatotic livers during late phases. HMGB1 lactylation and mtDNA-cGAS signaling emerge as key regulators. Machine perfusion (e.g. hypothermic oxygenated perfusion) reduces biliary complications via mitochondrial resuscitation outperforming conventional drug-based therapies.
Current single-pathway targeting shows limited efficacy due to IRI’s complexity. Future strategies should integrate temporal targeting (ferroptosis inhibitors pre-reperfusion; pyroptosis blockers post-reperfusion) DAMP-neutralizing agents (anti-HMGB1 antibodies) and precision preservation combining multi-omics biomarkers with ex vivo pharmacological preconditioning. Addressing metabolic vulnerabilities in fatty livers and refining cell death-specific interventions are critical for bridging translational gaps.
Yipishen Xiezhuo Jiedu Decoction in Ameliorating Kidney Damage Through miR-223/NLRP3/Caspase-1 Pathway
Hyperuricemia Nephropathy (HN) is an emerging metabolic disorder that predisposes individuals to Chronic Kidney Disease (CKD) yet effective treatments remain limited. Inflammation plays a pivotal role in HN-induced kidney injury with the NLRP3 inflammasome serving as a central mediator of this process. This study investigates the therapeutic effects of Yipishen Xiezhuo Jiedu Decoction (YPSXZJDD) a traditional Chinese medicine on HN-induced kidney injury through the miR-223/NLRP3/Caspase-1 pathway.
The key active components of YPSXZJDD were screened using UHPLC-Q Exactive Orbitrap-MS and a Protein-Protein Interaction (PPI) network diagram was constructed to explore potential mechanisms of action. The identified components were then utilized to intervene in both cellular and animal models of hyperuricemic nephropathy evaluating their therapeutic effects and underlying mechanisms.
Catalpol and Tanshinone IIA were identified as the key active components of YPSXZJDD. These compounds significantly mitigated renal epithelial cell apoptosis and inflammation by upregulating miR-223 which in turn inhibited the NLRP3/Caspase-1 pathway. The upregulation of miR-223 led to a marked reduction in NLRP3 activity and inflammatory responses thereby alleviating HN-induced kidney damage.
The findings of this study underscore the critical role of miR-223 in regulating the NLRP3 inflammasome and highlight its potential as a therapeutic target for HN. The inhibition of the NLRP3/Caspase-1 pathway by miR-223 significantly reduces inflammation and renal injury demonstrating the therapeutic efficacy of YPSXZJDD. These results offer a novel perspective on the application of traditional Chinese medicine in treating HN highlighting the importance of miR-223 in regulating inflammation.
This study demonstrates that YPSXZJDD alleviates HN-induced kidney injury by upregulating miR-223 and inhibiting the NLRP3/Caspase-1 pathway. The therapeutic potential of YPSXZJDD is supported by its ability to mitigate inflammation and renal damage offering a promising approach for HN treatment. Further research into the broader role of miR-223 in kidney disease and related conditions is warranted to expand the understanding of its therapeutic applications.
Immunocytes Play a Crucial Role as Mediators in the Protective Effects of D-β-Hydroxybutyrate Dehydrogenase 1 against Type 2 Diabetes Mellitus: A Mendelian Randomization Study
Observational studies suggest an association between the immune system and type 2 diabetes. The present study sought to ascertain the causal relationship between BDH1 and type 2 diabetes and investigate whether immunocytes mediate this relationship.
Appropriate single nucleotide polymorphisms (SNPs) were carefully selected from publicly available GWAS databases based on rigorous criteria to ensure the validity of the Mendelian randomization (MR) analysis. Inverse variance weighting (IVW) was employed as the primary approach for assessing effect sizes supplemented by four sensitivity analysis techniques: weighted median simple mode weighted mode and MR-Egger regression tests all aimed at ensuring the robustness and reliability of the IVW results. Reverse MR was conducted to confirm the feasibility of the mediation analysis. Lastly Cochran’s Q test MR Egger intercept regression and MR-PRESSO analysis were utilized to examine heterogeneity and horizontal pleiotropy.
The expression of BDH1 is inversely associated with the risk of type 2 diabetes with an odds ratio of 0.97 (95% CI: 0.95-0.99). IgD+ CD38+ B cell absolute count (20.7%) HLA DR on dendritic cell (18.7%) BAFF-R on CD20- CD38- B cell (9.5%) CD25 on IgD+ CD24+ B cell (4.1%) and BAFF-R on IgD+ B cell (3.4%) all exhibit certain mediating effects whereas IgD+ CD38+ B cell absolute count activated and resting CD4 regulatory T cell % CD4+ T cell transitional B cell absolute count CD28- CD8 dim T cell absolute count CD45 on HLA DR+ CD8+ T cell FSC-A on HLA DR+ natural killer and SSC-A on plasmacytoid dendritic cell exert masking effects.
The findings indicate that immunocytes could serve as a crucial mediating mechanism through which BDH1 exerts its protective effect against type 2 diabetes offering novel insights for the prevention and therapeutic management of the disease.
Diagnostic Biomarkers and Targeted Drug Prediction for Acute Kidney Injury: A Computational Approach
Acute Kidney Injury (AKI) is a clinical syndrome with rapid onset and poor prognosis and existing diagnostic methods suffer from low sensitivity and delay. To achieve early identification and precise intervention there is an urgent need to discover new precise biomarkers.
AKI samples were acquired from Gene Expression Omnibus (GEO) database. AKI-related module genes were identified using the “WGCNA” package. The “Limma” package was used to filter Differentially Expressed Genes (DEGs). Protein interaction networks were constructed by intersecting key modular genes with DEGs and six algorithms (MCC MNC Degree EPC Closeness and Radiality) in the cytoHubba plug-in were combined to screen candidate genes. Diagnostic biomarkers were cross-screened using LASSO regression with Support Vector Machine–Recursive Feature Elimination (SVM-RFE) machine learning algorithm and their predictive performance was verified by Receiver Operating Characteristic (ROC) analysis. Transcription Factors (TFs) regulatory network was constructed applying Cytoscape 3.8.0. Finally the prediction and molecular docking analysis of potential target drugs were performed using the DSigDB database and AutoDockTools.
A total of 498 key modular genes significantly associated with AKI were screened and 88 AKI-related DEGs and 18 candidate genes were further identified. Importantly four biomarkers with high diagnostic value (DDX17 FUBP1 PABPN1 and SF3B1) were screened and validated using dual machine learning algorithms including LASSO regression and SVM-RFE. The area under the ROC curve (AUC) values for these biomarkers were greater than 0.8 indicating good predictive performance. Moreover 19 TFs and 17 miRNA of SF3B1 10 TFs and 58 miRNA of PABPN1 15 TFs and 60 miRNA of FUBP1 together with 13 TFs and 109 miRNA of DDX17 were screened. Drug prediction and molecular docking analysis revealed that Demecolcine and Testosterone Enanthate stably bind to certain markers.
Four potential biomarkers closely related to AKI were identified which may be involved in the occurrence and progression of AKI by regulating key processes such as transcription. The predicted Demecolcine and Testosterone Enanthate may also be involved in the repair of renal injury by regulating key target genes. Although further experimental validation is still needed these may still provide new intervention strategies for the treatment of AKI.
To conclude four AKI biomarkers with high diagnostic value were screened by integrating multiple computational methods revealing a new perspective on the molecular mechanism of AKI. The results provided a new theoretical basis for achieving early precision diagnosis and individualized treatment of AKI.
Revolutionizing Antibiotic Delivery: Harnessing 3D-Printing Technology to Combat Bacterial Resistance
Antibiotic resistance poses a significant threat to public health rendering many life-saving medications ineffective as pathogenic microorganisms develop resistance spontaneously. This results in infections that are difficult to treat with limited or no treatment options. Traditionally addressing this challenge involves developing new pharmaceuticals a lengthy and costly process. However a more efficient approach lies in improving drug delivery methods which can be quicker and more economical. In recent years 3D printing technology has emerged as a groundbreaking industry-accepted technique that enables the affordable simple and rapid manufacturing of pharmaceuticals. This technology supports iterative design-build-test cycles facilitating the development of a wide range of products from simple 3D-printed tablets to complex medical devices tailored for diverse applications. This article explores innovative strategies in the search for novel antibiotics the development of more effective preventative measures and crucially a deeper understanding of the ecology of antibiotics and antibiotic resistance. It provides an overview of these issues' historical and current status emphasizing the potential of 3D printing to address antibiotic resistance. Additionally it discusses how to expand conceptual frameworks in response to recent advancements in chemotherapy antimicrobials and antibiotic resistance. The article highlights various notable efforts in utilizing 3D printing to develop antimicrobial dosage forms and medical devices offering insights into future possibilities.
Recent Advancements in Stimuli-Responsive Polymeric Implants Fabricated via Additive Manufacturing: A Review
This review discusses the latest progress in using smart polymeric materials for making medical implants with advanced three-dimensional (3D) and four-dimensional (4D) printing techniques. These smart polymers also known as stimuli-responsive polymers can change their properties when exposed to external triggers like temperature pH light or magnetic fields. Integrating these materials with 3D/4D printing allows the creation of highly customizable and functional implants that can adapt to the body's environment. This means implants can now perform additional tasks such as releasing drugs or changing shape when needed. The review covers different 3D/4D printing methods the types of smart polymers available and the benefits of using these materials in medical implants. It also addresses the challenges faced in developing these advanced implants such as finding suitable materials that are safe for the body and ensuring precise manufacturing. The future prospects of these innovative implants are promising with potential applications in personalized medicine and non-invasive treatments. This review aims to provide a detailed analysis of recent advancements in stimuli-responsive polymeric materials utilized in additive manufacturing of medical implants. The objective is to explore these materials' clinical implications address the unique challenges in their development and fabrication and outline their future potential in enhancing personalized and non-invasive medical treatments.
Cancer Management Using Photodynamic Therapy: Fundamentals, Mechanism and Advances
PDT is a common and minimally invasive treatment used for certain types of cancer. Photodynamic therapy involves the generation of reactive oxygen species resulting in cellular apoptosis and disruption of the tumor microenvironment. This review presents a comprehensive examination of recent developments in Photodynamic Therapy (PDT) detailing its mechanisms the importance of photosensitizers and their applications across various cancer types. Photosensitizers are essential in photodynamic therapy as they generate reactive oxygen species when exposed to light. Advanced photosensitizers demonstrate high conversion efficiency improved tumor specificity and reduced adverse effects. Recent advancements have led to the creation of photosensitizers that exhibit enhanced solubility stability and the ability to selectively accumulate in tumors. Combination therapies that incorporate PDT exhibit notable therapeutic outcomes indicating substantial progress in the field. Recent developments in photodynamic therapy particularly those that boost immune responses show considerable promise in significantly enhancing the effectiveness of tumor elimination. These advancements have the potential to enhance the therapeutic application of photodynamic therapy offering new possibilities for cancer treatment.
Binding Interaction and Stability Analysis of Quercetin and its Derivatives as Potential Inhibitors of Triple Negative Breast Cancer (TNBC) against PARP1 Protein: An in-silico Study
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen and progesterone receptors (ER PR) and low or absent HER2 expression limiting treatment options. Quercetin a flavonoid with anti-cancer properties has the potential to be a therapeutic intervention.
The study aimed to explore the potential of Quercetin derivatives as therapeutic agents for TNBC using several computational methods.
The study utilized PASS prediction molecular docking ADMET prediction QSAR models MD simulations binding free energy and DFT calculations to evaluate the efficacy of quercetin derivatives.
ADMET analysis confirmed the solubility non-carcinogenicity and low toxicity of four quercetin derivatives: LM01 LM02 LM05 and LM10. These derivatives exhibited strong binding affinity against TNBC protein PPAR1 with binding energies of -10.6 -10.7 -11.4 and -10 kcal/mol respectively. MD simulations confirmed their stability with consistent RMSD values and favorable RMSF values. Post-simulation calculations and reduced HOMO-LUMO energy gaps further supported their potential as promising candidates.
Our computational findings suggest that quercetin derivatives particularly LM01 LM02 and LM10 exhibit strong stability and binding affinity positioning them as promising candidates for TNBC treatment. Further experimental validation is required to confirm their therapeutic potential.
Porphyrin-based MOFs for Gene Delivery in Cancer Therapy: Recent Advances and Progress
Cancer is one of the leading causes of death worldwide which involves the uncontrolled growth of body cells. Cytotoxic chemotherapy drugs such as tamoxifen doxorubicin methotrexate and cisplatin have shortcomings that have deprived these treatments of the desired efficiency to destroy tumor cells. Poor pharmacokinetics severe side effects and low targeting properties are examples of these shortcomings. Meanwhile in the last few years the use of nanocarriers in drug delivery systems has grown significantly. Porphyrins also called life pigments are classified as organic complexes. Due to their unique electrochemical and photophysical properties they have been used in various fields such as photodynamic therapy fluorescence and photoacoustic imaging. However due to the limitations of these compounds in aqueous environments such as aggregation by surface molecules weak absorption in the biological spectral window self-quenching and poor chemical and optical stability there are gaps in the clinical applications of porphyrins. To overcome these challenges researchers have developed porphyrin-based MOFs. Metal-organic frameworks (MOFs) made of metal ions and clusters coupled with organic linkers such as porphyrins through self-assembly retain the properties of porphyrins while offering additional advantages. Several synthetic approaches and significant advances have been made in the development of porphyrin-based MOFs including combination therapies advanced drug delivery cancer therapy and photodynamic therapy. Porphyrin-based metal-organic frameworks represent a transformative approach in cancer treatment by integrating multiple therapeutic functions improving targeting mechanisms ensuring safety increasing drug delivery efficiency and overcoming tumor biological barriers such as hypoxia and their day-to-day development promises the formation of more personalized and effective strategies.