Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Objective: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. Methods: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. Results: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

Objective: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. Methods: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. Results: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

Objective: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. Methods: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. Results: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

Objective: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. Methods: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. Results: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

Objective: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. Methods: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. Results: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway’s critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. Conclusion In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

Accurate receptor/ligand binding free energy calculations can greatly accelerate drug discovery by identifying highly potent ligands. By simulating the change from one compound structure to another, the relative binding free energy (RBFE) change can be calculated based on the theoretically rigorous free energy perturbation (FEP) method. However, existing FEP-RBFE approaches may face convergence challenges due to difficulties in simulating non-physical intermediate states, which can lead to increased computational costs to obtain the converged results. To fundamentally overcome these issues and accelerate drug discovery, a new combined-structure RBFE (CS-FEP) calculation strategy was proposed, which solved the existing issues by constructing a new alchemical pathway, smoothed the alchemical transformation, increased the phase-space overlap between adjacent states, and thus significantly increased the convergence and accelerated the relative binding free energy calculations. This method was extensively tested in a practical drug discovery effort by targeting phosphodiesterase-1 (PDE1). Starting from a PDE1 inhibitor (compound 9, IC₅₀ = 16.8 μmol/L), the CS-FEP guided hit-to-lead optimizations resulted in a promising lead (11b and its mesylate salt formulation 11b-Mesylate, IC₅₀ = 7.0 nmol/L), with ∼2400-fold improved inhibitory activity. Further experimental studies revealed that the lead showed reasonable metabolic stability and significant anti-fibrotic effects in vivo.

Foodborne pathogens are one of the major factors leading to food safety issues, causing harm to the national economy and people's livelihood. Achieving rapid detection of foodborne pathogens is currently a key strategy for preventing and controlling foodborne diseases. Antibodies naturally possess high specificity and sensitivity, serving as preferred tools for specific recognition of foodborne pathogens. We list the main methods for detecting foodborne pathogens, introduce the evolution and development of polyclonal antibodies, monoclonal antibodies, and genetically engineered antibodies, and review the application of different antibody technologies in the rapid detection of foodborne pathogens. Furthermore, we recognize that the combination of antibody technology and other foodborne pathogen detection methods is currently a reliable means to improve detection performance. Finally, we elaborate on the existing limitations of different antibodies and summarize the current research status and potential issues, aiming to provide a theoretical basis and practical ideas for the development of rapid detection of foodborne pathogens.
Foodborne Diseases/prevention & control* ; Food Microbiology ; Antibodies, Monoclonal/biosynthesis* ; Antibodies/immunology* ; Humans ; Food Contamination/analysis*

Objective:To investigate the efficacy and safety of radium-223 in combination with new-generation hormonal agents in patients with bone metastases of prostate cancer.Methods:The clinical data of 17 patients (12 from the First Affiliated Hospital of Airforce Military Medical University and 5 from Xi'an International Medical Center Hospital) with metastatic castration-resistant prostate cancer(mCRPC) treated by radium-223 combined with new-generation hormonal agents from January 2021 to June 2022 were retrospectively analyzed. In all cases, the average age was (73.3±8.5) years old. Before treatment, the median prostate-specific antigen (PSA) was 15.7 (3.2, 36.5) ng/ml, the median alkaline phosphatase (ALP) was 131.5 (79.0, 430.7) U/L. All patients had ≥ 2 bone metastases but no visceral or lymph node metastases. The median number of bone scan lesions was 10(8, 15). Bone pain symptom was present in 16(94.1%) patients. There were 9 cases (52.9%) with Eastern Cooperative Oncology Group (ECOG) score of ≥2, 1 case (5.9%) with ECOG score of 1 and 6 cases (35.2%) with ECOG score of 0. All patients were treated with radium-223 (55 kBq/kg, injected every 4 weeks for a maximum of 6 cycles), of which 5 patients were combined with enzalutamide, 8 patients combined with apatamide and 4 patients combined with bicalutamide. PSA response (PSA decreased by ≥30% from baseline and maintained for at least 1 month), ALP response (ALP decreased by ≥30% from baseline and maintained for at least 1 month) and pain relief rates were analyzed. Imaging evaluation was performed before and after treatment to calculate the objective response rate of metastases. The incidence of treatment-related adverse effects and skeletal related event (SRE) were also recorded.Results:Eleven patients completed 6 courses, 3 patients completed 5 courses and 3 patients completed ≥4 courses. The median ALP after 1 month of last treatment was 83.2 (51.5, 126.5) U/L, which was significantly decreased than baseline. 12 patients (70.6%) showed an ALP response and the other 5 (29.4%) showed varying degrees of ALP elevation. PSA response was observed in 4 patients (23.5%), of which 2 (11.8%) had a continuous decrease and 2 (11.8%) had a late-stage increase in PSA. Pain relief was relieved in 15 cases (88.2%) during treatment, 1 case (5.9%) had worsening pain due to disease progression and 1 case (5.9%) had no change during treatment. The ECOG score decreased in 15 (88.2%) patients. The median number of bone metastases in patients decreased to 5 (4, 9). One patient (5.9%) had complete remission during treatment, 11 patients (64.7%) had a partial response, 4 patients (23.5%) were stable, and 1 (5.9%) showed imaging progression after 4 months of treatment. The overall objective remission response rate was 70.5% (12/17). Treatment-related hematologic adverse effects included anemia (1 case, 5.9%, grade 3), thrombocytopenia (1 case, 5.9%, grade 3) and leukopenia (1 case, 5.9%, grade 2). Non-hematologic adverse effects included fatigue (3 cases, 17.6%, 2 cases in grade 1, 1 case in grade 2), gastrointestinal bleeding (1 case, 5.9%, grade 3), diarrhea (1 case, 5.9%, grade 2) and fever (1 case, 5.9%, grade 1). Patients with grades 1 to 2 relieved with symptomatic management. Three cases (17.6%) were discontinued due to intolerance of grade 3 adverse reactions and 1 case (5.9%) terminated on its own. There was no SRE during treatment and follow-up.Conclusions:Radium-223 combined with New-generation hormonal agents has a high objective remission rate in patients with mCRPC, which could provide pain relief and improve quality of life. The incidence of adverse reactions was low and well tolerated.

Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference (P<0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95%CI=0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.
Humans ; Thyroid Nodule/diagnostic imaging* ; Biopsy, Fine-Needle/methods* ; Reproducibility of Results ; Ultrasonography ; Retrospective Studies ; Thyroid Neoplasms