Total Synthesis of the Potent and Broad-Spectrum Antibiotics Amycolamicin and Kibdelomycin.

The complex and intriguing structures of the antibiotics amycolamicin and kibdelomycin are herein confirmed through total synthesis. Careful titration of the synthetic products reveals that kibdelomycin is the salt form of amycolamicin. This synthesis employs a highly convergent strategy, which provides a modular approach for further SAR studies of this class of antibiotics.

Macrophages-derived exosomal lncRNA LIFR-AS1 promotes osteosarcoma cell progression via miR-29a/NFIA axis.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in young people. Tumor-associated macrophages (TAMs) have been reported to play an important role in the development of osteosarcoma. However, the detailed molecular mechanisms remain largely unknown and need to be elucidated. Recently, exosomes have been reported as the crucial mediator between tumor cells and the tumor microenvironment. And a lot of lncRNAs have been reported to act as either oncogenes or tumor suppressors in osteosarcoma. In this research, we aim to explore the role of macrophages-derived exosomal lncRNA in osteosarcoma development and further elucidated the potential molecular mechanisms involved. METHODS: TAMs were differentiated from human mononuclear cells THP-1, and a high-throughput microarray assay was used to analyze the dysregulated lncRNAs and miRNAs in osteosarcoma cells co-cultured with macrophages-derived exosomes. Western blot, qRT-PCR assays, and Dual-luciferase reporter assay were used to verify the interaction among LIFR-AS1, miR-29a, and NFIA. Cck-8, EdU, colony formation assay, wound-healing, and transwell assay were performed to explore the characterize the proliferation and metastasis ability of OS cells. And qPCR, Western blots, immunohistochemistry, and cell immunofluorescence were used to detect the expression of relative genes or proteins. RESULTS: In this study, we found that THP-1-induced macrophage-derived exosomes could facilitate osteosarcoma cell progression both in vitro and in vivo. Then, the results of the high-throughput microarray assay showed that LIFR-AS1 was highly expressed and miR-29a was lowly expressed. Furthermore, LIFR-AS1 was identified as a miR-29a sponge, and NFIA was validated as a direct target of miR-29a. Functional assays demonstrated that knockdown of exosomal LIFR-AS1 could attenuate the promotion effects of macrophages-derived exosomes on osteosarcoma cell progression and miR-29a inhibition could reserve the effect of LIFR-AS1-knockdown exosomes. Correspondingly, NFIA-knockdown could partially reverse the tumor inhibition effect of miR-29a on osteosarcoma cells. CONCLUSIONS: Taken together, macrophages-derived exosomal lncRNA LIFR-AS1 can promote osteosarcoma cell proliferation, invasion, and restrain cell apoptosis via miR-29a/NFIA axis, which can act as a potential novel therapeutic target for osteosarcoma therapy.

The effectiveness of combination therapies for androgenetic alopecia: A systematic review and meta-analysis.

Androgenetic alopecia (AGA) is the most common type of baldness affecting both men and women. Studies investigating combination therapies for AGA reported greater efficacy than monotherapy but without rigorous examination. The authors performed a meta-analysis and systemic review to further verify the evidence. To evaluate the effectiveness of three common combination therapies of minoxidil with finasteride, low-level laser light therapy (LLLT) or microneedling versus minoxidil monotherapy. We conducted a systematic review of randomized controlled trials (RCTs) of combination therapies consisting of topical minoxidil for AGA through April 2020. Quality assessment and data analysis were performed by Review Manager 5.3. Fifteen studies met the inclusion criteria involving a total of 1172 AGA patients. We conducted meta-analysis for three groups of combined treatment separately, and all were superior to monotherapy in terms of global photographic assessment (P < .05). Combination of LLLT or microneedling with minoxidil also showed significant increase in hair count (P < .05) compared to monotherapy. The present study suggests that combination therapy could be an effective, safe and promising option for the treatment of AGA. However, more RCTs are needed to further investigate and confirm the efficacy of combined treatment.

Spatial and temporal variations in non-point source losses of nitrogen and phosphorus in a small agricultural catchment in the Three Gorges Region.

Losses of agricultural pollutants from small catchments are a major issue for water quality in the Three Gorges Region. Solutions are urgently needed. However, before pollutant losses can be controlled, information about spatial and temporal variations in pollutant losses is needed. The study was carried out in the Wangjiagou catchment, a small agricultural catchment in Fuling District, Chongqing, and the data about non-point source losses of nitrogen and phosphorus was collected here. Water samples were collected daily by an automatic water sampler at the outlets of two subcatchments from 2012 to 2014. Also, samples of surface runoff from 28 sampling sites distributed through the subcatchments were collected during 12 rainfall events in 2014. A range of water quality variables were analyzed for all samples and were used to demonstrate the variation in non-point losses of nitrogen and phosphorus over a range of temporal and spatial scales and in different types of rainfall in the catchment. Results showed that there was a significant linear correlation between the mass concentrations of total nitrogen (TN) and nitrate (NO3-N) in surface runoff and that the relationship was maintained with changes in time. Concentrations of TN and NO3-N peaked after fertilizer was applied to crops in spring and autumn; concentrations decreased rapidly after the peak values in spring but declined slowly in autumn. N and P concentrations fluctuated more and showed a greater degree of dispersion during the spring crop cultivation period than those in autumn. Concentrations of TN and NO3-N in surface runoff were significantly and positively correlated with the proportion of the area that was planted with corn and mustard tubers, but were negatively correlated with the proportion of the area taken up with rice and mulberry plantations. The average concentrations of TN and NO3-N in surface runoff reached the highest level from the sampling points at the bottom of the land used for corn only, but lowest in rice fields. Slope gradient had a significant positive correlation with TN's and total phosphorus (TP)'s concentration losses. Concentrations of TN, NO3-N, and total phosphorus were significantly correlated with rainfall. Peak concentrations of ammoniacal nitrogen occurred during the fertilizer application period in spring and autumn. Different structures of land use types had a significant influence on the concentration losses of nitrogen and phosphorus; thus, using a reasonable way to adjust land use structure and spatial arrangement of whole catchment was an effective solution to control non-point source pollution of the Three Gorges Region.

Enhancing activity and stability of FeNC catalysts through co incorporation for oxygen reduction reaction.

FeNC single atom catalysts (SACs) have attracted great interest due to their highly active FeN4 sites. However, the pyrolysis treatment often leads to inevitable metal migration and aggregation, which reduces the catalytic activity. Moreover, due to the Fenton reaction caused by FeNC in alkaline and acidic solutions, the presence of Fe and peroxide in electrodes may generate free radicals, resulting in serious degradation of the organic ionomer and the membrane. Herein, we report an original strategy of introducing Co single atoms into FeNC catalysts, forming atomically dispersed bimetallic active sites (FeCoNC) and improving the activity and stability of the catalyst. Benefiting from this strategy, FeCoNC catalyst exhibits excellent oxygen reduction reaction (ORR) activity in alkaline media (E1/2 = 0.88 V) and in acidic media (E1/2 = 0.77 V). As the cathode of Zn-air battery (ZAB), FeCoNC shows an excellent peak power density of 142.8 mW cm-2 and a specific capacity of 806.6 mAh/gZn. This work provides a novel avenue to optimize and enhance the ORR performance of atomic dispersed FeNC catalysts.

Direct contact between tumor cells and platelets initiates a FAK-dependent F3/TGF-ß positive feedback loop that promotes tumor progression and EMT in osteosarcoma.

Platelets have received growing attention for their roles in hematogenous tumor metastasis. However, the tumor-platelet interaction in osteosarcoma (OS) remains poorly understood. Here, using platelet-specific focal adhesion kinase (FAK)-deficient mice, we uncover a FAK-dependent F3/TGF-ß positive feedback loop in OS. Disruption of the feedback loop by inhibition of F3, TGF-ß, or FAK significantly suppresses OS progression. We demonstrate that OS F3 initiated the feedback loop by increasing platelet TGF-ß secretion, and platelet-derived TGF-ß promoted OS F3 expression in turn and modulated OS EMT process. Immunofluorescence results indicate platelet infiltration in OS niche and we verified it was mediated by platelet FAK. In addition, platelet FAK was proved to mediate platelet adhesion to OS cells, which was vital for the initiation of F3/TGF-ß feedback loop. Collectively, these findings provide a rationale for novel therapeutic strategies targeting tumor-platelet interplay in metastatic OS.

Nanosized drug delivery strategies in osteosarcoma chemotherapy.

Despite recent developments worldwide in the therapeutic care of osteosarcoma (OS), the ongoing challenges in overcoming limitations and side effects of chemotherapy drugs warrant new strategies to improve overall patient survival. Spurred by rapid progress in biomedicine, nanobiotechnology, and materials chemistry, chemotherapeutic drug delivery in treatment of OS has become possible in recent years. Here, we review recent advances in the design of drug delivery system, especially for chemotherapeutic drugs in OS, and discuss the relative merits in trials along with future therapeutic options. These advances may pave the way for novel therapies requisite for patients with OS.

Dural Reconstruction Materials for the Repairing of Spinal Neoplastic Cerebrospinal Fluid Leaks.

Spinal tumors often lead to more complex complications than other bone tumors. Nerve injuries, dura mater defect, and subsequent cerebrospinal fluid (CSF) leakage generally appear in spinal tumor surgeries and are followed by serious adverse outcomes such as infections and even death. The use of suitable dura mater replacements to achieve multifunctionality in fluid leakage plugging, preventing adhesions, and dural reconstruction is a promising therapeutic approach. Although there have been innovative endeavors to manage dura mater defects, only a handful of materials have realized the targeted multifunctionality. Here, we review recent advances in dura repair materials and techniques and discuss the relative merits in both preclinical and clinical trials as well as future therapeutic options. With these advances, spinal tumor patients with dura mater defects may be able to benefit from novel treatments.

Tocilizumab (monoclonal anti-IL-6R antibody) reverses anlotinib resistance in osteosarcoma.

Purpose: Anlotinib, a tyrosine kinase inhibitor (TKI) has been in clinical application to inhibit malignant cell growth and lung metastasis in osteosarcoma (OS). However, a variety of drug resistance phenomena have been observed in the treatment. We aim to explore the new target to reverse anlotinib resistance in OS. Materials and Methods: In this study, we established four OS anlotinib-resistant cell lines, and RNA-sequence was performed to evaluate differentially expressed genes. We verified the results of RNA-sequence by PCR, western blot and ELISA assay. We further explored the effects of tocilizumab (anti- IL-6 receptor), either alone or in combined with anlotinib, on the inhibition of anlotinib-resistant OS cells malignant viability by CCK8, EDU, colony formation, apoptosis, transwell, wound healing, Cytoskeletal stain assays, and xenograft nude mouse model. The expression of IL-6 in 104 osteosarcoma samples was tested by IHC. Results: We found IL-6 and its downstream pathway STAT3 were activated in anlotinib-resistant osteosarcoma. Tocilizumab impaired the tumor progression of anlotinib-resistant OS cells, and combined treatment with anlotinib augmented these effects by inhibiting STAT3 expressions. IL-6 was highly expressed in patients with OS and correlated with poor prognosis. Conclusion: Tocilizumab could reverse anlotinib resistance in OS by IL-6/STAT3 pathway and the combination treatment with anlotinib rationalized further studies and clinical treatment of OS.

The malignancy of chordomas is enhanced via a circTLK1/miR-16-5p/Smad3 positive feedback axis.

CircRNAs play crucial roles in various malignancies via an increasing number of reported regulatory mechanisms, including the classic sponging mechanism between circRNAs and micro RNAs (miRNAs). We performed bioinformatic analyses and identified circTLK1 as a regulator of malignant chordoma progression. Moreover, we observed that circTLK1 showed high expression in chordoma cells and tissues, while circTLK1 interference suppressed chordoma cell proliferation and invasion. In addition, circTLK1 directly interacted with miR-16-5p, which has previously been shown to repress chordoma, and circTLK1 knockdown suppressed Smad3 expression. Chromatin immunoprecipitation sequencing further demonstrated that Smad3 acts as a positive regulator by interacting with TLK1, thereby mediating the circTLK1/miR-16-5p/Smad3 positive feedback axis. Taken together, our findings suggested that the disruption of the circTLK1/miR-16-5p/Smad3 positive feedback pathway, particularly via the Smad3 inhibitor SIS3, could be a promising therapeutic strategy.

Drug-Loaded Zwitterion-Based Nanomotors for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) treatment requires a nanosystem for drug delivery that can effectively penetrate the blood-spinal cord barrier (BSCB). Herein, we designed poly(2-methacryloyloxyethyl phosphorylgallylcholine) (PMPC)/l-arginine (PMPC/A)-based nanomotors that can release nitric oxide (NO). The nanomotors were loaded with the inducible NO synthase inhibitor 1400W and nerve growth factor (NGF). PMPC with a zwitterionic structure not only provided good biocompatibility for the nanomotors but also facilitated their passage through the BSCB owing to the assistance of a large number of choline transporters on the BSCB. Additionally, the l-arginine loaded on the nanomotors was able to react with reactive oxygen species in the microenvironment of the injured nerve to produce NO, thereby conferring the ability of autonomic movement to the nanomotors, which facilitated the uptake of drugs by cells in damaged areas and penetration in pathological tissues. Moreover, in vivo animal experiments indicated that the PMPC/A/1400W/NGF nanomotors could effectively pass through the BSCB and restore the motion function of a rat SCI model by regulating its internal environment as well as the release of therapeutic drugs. Thus, the drug delivery system based on nanomotor technology offers a promising strategy for treating central nervous system diseases.

The COPS3-FOXO3 positive feedback loop regulates autophagy to promote cisplatin resistance in osteosarcoma.

Chemotherapy is an important treatment modality for osteosarcoma (OS), but the development of chemoresistance limits the therapeutic efficacy of OS and results in a poor prognosis. Thus, a better understanding of the mechanisms underlying chemoresistance in OS is essential. We previously demonstrated that COPS3/CSN3 (COP9 signalosome subunit 3) functions as an oncogene to promote OS cells lung metastasis, which is closely related to chemoresistance. Here, we showed that COPS3 was significantly upregulated in OS tissues with poor response to preoperative chemotherapy. Moreover, COPS3 depletion made OS cells more sensitive to cisplatin treatment in vitro and in vivo, implicating COPS3 as a driver of cisplatin resistance. Mechanistic investigations showed that COPS3 induced a cytoprotective macroautophagy/autophagy in response to cisplatin. Specifically, we identified FOXO3 as a critical target of COPS3, as high expression of COPS3 enhanced the nuclear abundance of FOXO3 and increased the expression of FOXO3-responsive genes, promoting autophagosome formation and maturation. In turn, FOXO3 regulated COPS3 levels by inhibiting ubiquitin-mediated degradation and attenuating SKP2-mediated COPS3 inhibition, cooperatively maintaining a high level of COPS3. In both COPS3-expressing OS cells and a murine xenograft model, inhibition of autophagy could also overcome resistance to cisplatin. Collectively, our results offer insights into the mechanisms of cisplatin resistance and suggest that targeting COPS3-mediated autophagy is a promising therapeutic strategy for overcoming the cisplatin resistance of OS.Abbreviations: 3-MA: 3-methyladenine; BECN1: beclin 1; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; COPS3/CSN3: COP9 signalosome subunit 3; CQ: chloroquine; DEGs: differentially expressed genes; FOXO3: forkhead box O3; GFP: green fluorescent protein; IC50: 50% inhibitory concentration; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; mRFP: monomeric red fluorescent protein; OS: osteosarcoma; PBS: phosphate-buffered saline; qRT-PCR: quantitative real-time PCR; RAB7: RAB7, member RAS oncogene family; RPS6KB1/p70S6K1: ribosomal protein S6 kinase B1; SEM: standard error of the mean; shRNA: short hairpin RNA; siRNA: small interfering RNA; SKP2: S-phase kinase associated protein 2; TEM: transmission electron microscopy; UPS: ubiquitin-proteasome system.

Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy.

OBJECTIVES: The fact that studies on anti-programmed cell death 1 (PD-1) or its relevant ligand 1 (PD-L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various checkpoint molecules with immunohistochemistry in osteosarcoma specimens and analyzed the relationship of the expression of these checkpoint molecules with patients' clinical courses. METHODS: This study was a retrospective non-intervention study from August 1st 2017 to March 1st 2020. Immunohistochemistry for B7-H3 (CD276, Cluster of Differentiation 276), CD47 (Cluster of Differentiation 47), PD-L1 (programmed cell death ligand 1), TIM3 (mucin-domain containing-3), TGF-ß (TransformingGrowth Factor ß), CXCR 4 (Chemokine Receptor 4), CD27 (Cluster of Differentiation 27), IDO1 (Indoleamine 2,3-dioxygenase 1), KIRs (Killer cell Immunoglobulin-like Receptors), and SDF-1 (Stromal cell-Derived Factor-1) was performed on 35 resected osteosarcoma specimens. Patients progressed upon first-line chemotherapy with evaluable lesions were qualified for this study, and their specimens previously stored in the pathological department repository would be retrieved for analysis. Associations between the immunohischemistry markers and clinicopathological variables and survival were evaluated by the χ2 displayed by cross-table, Cox proportional hazards regression model, and Kaplan-Meier plots. RESULTS: The positive rates of B7-H3, CD47, PD-L1, TIM3, and TGF-ß expression in this sample of 35 heavily treated osteosarcomas were 29% (10/35), 15% (5/35), 9% (3/35), 6% (2/35), and 6% (2/35), respectively, and diverse staining intensities were observed. Among these advanced patients, 15/35 (43%) had positive checkpoint expression, of which 33% (5/15) showed evidence of the co-expression of more than one checkpoint molecule. We did not find any obvious correlation with clinicopathological characteristics and the positive expression of these molecules. CONCLUSIONS: The present study highlights that only a small subset of progressive osteosarcomas, which had been heavily-treated, expressed tumor immune-associated checkpoint molecules, of which B7-H3 was the most positively expressed checkpoint and might be a promising target for further osteosarcoma investigation.

Chemotactic NO/H2S Nanomotors Realizing Cardiac Targeting of G-CSF against Myocardial Ischemia-Reperfusion Injury.

Recombinant granulocyte colony-stimulating factor (G-CSF), with a direct repair effect on injured cardiomyocytes against myocardial infarction ischemia-reperfusion-injury (IRI), displays a poor effect owing to the limited cardiac targeting efficacy. There are almost no reports of nanomaterials that deliver G-CSF to the IRI site. Herein, we propose a way to protect G-CSF by constructing one layer of nitric oxide (NO)/hydrogen sulfide (H2S) nanomotors on its outside. NO/H2S nanomotors with specific chemotactic ability to high expression of reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) at the IRI site can deliver G-CSF to the IRI site efficiently. Meanwhile, superoxide dismutase is covalently bound to the outermost part, reducing ROS at the IRI site through a cascade effect with NO/H2S nanomotors. The synergistic effect between NO and H2S on the effective regulation of the IRI microenvironment can not only avoid toxicity caused by excessive concentration of a single gas but also reduce inflammation level and relieve calcium overload, so as to promote G-CSF to play a cardioprotective role.

Chordoma recruits and polarizes tumor-associated macrophages via secreting CCL5 to promote malignant progression.

BACKGROUND: Chordoma is an extremely rare, locally aggressive malignant bone tumor originating from undifferentiated embryonic remnants. There are no effective therapeutic strategies for chordoma. Herein, we aimed to explore cellular interactions within the chordoma immune microenvironment and provide new therapeutic targets. METHODS: Spectrum flow cytometry and multiplex immunofluorescence (IF) staining were used to investigate the immune microenvironment of chordoma. Cell Counting Kit-8, Edu, clone formation, Transwell, and healing assays were used to validate tumor functions. Flow cytometry and Transwell assays were used to analyze macrophage phenotype and chemotaxis alterations. Immunohistochemistry, IF, western blot, PCR, and ELISA assays were used to analyze molecular expression. An organoid model and a xenograft mouse model were constructed to investigate the efficacy of maraviroc (MVC). RESULTS: The chordoma immune microenvironment landscape was characterized, and we observed that chordoma exhibits a typical immune exclusion phenotype. However, macrophages infiltrating the tumor zone were also noted. Through functional assays, we demonstrated that chordoma-secreted CCL5 significantly promoted malignancy progression, macrophage recruitment, and M2 polarization. In turn, M2 macrophages markedly enhanced the proliferation, invasion, and migration viability of chordoma. CCL5 knockdown and MVC (CCL5/CCR5 inhibitor) treatment both significantly inhibited chordoma malignant progression and M2 macrophage polarization. We established chordoma patient-derived organoids, wherein MVC exhibited antitumor effects, especially in patient 4, with robust killing effect. MVC inhibits chordoma growth and lung metastasis in vivo. CONCLUSIONS: Our study implicates that the CCL5-CCR5 axis plays an important role in the malignant progression of chordoma and the regulation of macrophages, and that the CCL5-CCR5 axis is a potential therapeutic target in chordoma.

Mediation of mechanically adapted TiCu/TiCuN/CFR-PEEK implants in vascular regeneration to promote bone repair in vitro and in vivo.

Background/Objective: TiCu/TiCuN is a multilayer composite coating comprising TiN and Cu, which provides excellent wear resistance and antibacterial properties. However, its applicability as a functional coating has not been widely realised, and several aspects pertaining to its properties must still be explored. Methods: This study uses arc ion-plating technology to apply a TiCu/TiCuN coating on the surface of carbon fibre-reinforced (CFR) polyetheretherketone (PEEK) material.The safety and osteogenic activity of TiCu/TiCuN-coated CFR-PEEK materials were explored through cell experiments and animal experiments, and the molecules behind them were verified. Results: The new material exhibits improved mechanical compatibility (mechanical strength and elastic modulus) and superior light transmittance (elimination of metal artifacts and ray refraction during radiology and radiotherapy). The proposed implant delivers excellent biocompatibility for mesenchymal stem cells and human umbilical vein endothelial cells (HUVECs), and it exhibits excellent osteogenic activity both in vitro and in vivo. Additionally, it was determined that the applied TiCu/TiCuN coating aids in upregulating the expression of angiogenesis-related signals (i.e., cluster-of-differentiation 31, α-smooth muscle actin, vascular endothelial growth factor receptor, and hypoxia-inducible factor-1α) to promote neovascularisation, which is significant for characterising the mechanism of the coating in promoting bone regeneration. Conclusion: The current results reveal that the TiCu/TiCuN-coated CFR-PEEK implants may emerge as an advanced generation of orthopaedic implants. Translational potential statement: The results of this study indicate that TiCu/TiCuN coating-modified CFR-PEEK materials can promote bone repair through angiogenesis and have broad clinical translation prospects.

Current progress and open challenges for applying tyrosine kinase inhibitors in osteosarcoma.

Osteosarcoma (OS) is a mesenchymal-origin tumor that constitutes the most common primary malignant bone tumor. The survival rate of the patients has significantly improved since the introduction of neoadjuvant chemotherapy and extensive resection, but it has stagnated in recent 40 years. Tyrosine kinase inhibitors (TKIs) have played a key part in the treatment of malignant tumors. In advanced OS, TKIs including anlotinib, apatinib, sorafenib, etc. have significantly improved the progression-free survival of patients, while the overall survival remains unchanged. The main reason is the rapid and inevitable progress of acquired drug resistance of OS. However, as the application of TKIs in OS and other tumors is still in the exploratory phase, its drug resistance mechanism and corresponding solutions are rarely reported. Hence, in this review, we summarize knowledge of the applications of TKIs, the mechanism of TKIs resistance, and the attempts to overcome TKIs resistance in OS, which are the three potentially novel insights of TKIs in OS. Because most evidence is derived from studies using animal and cell models, we also reviewed clinical trials and related bioinformatics data available in public databases, which partially improved our understanding of TKIs applications.

Exploring the Effect of Polyphyllin I on Hepatitis B Virus-related Liver Cancer through Network Pharmacology and in vitro Experiments.

AIM AND OBJECTIVE: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. MATERIALS AND METHODS: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. RESULTS: Bioinformatics analysis found that PPI had a total of 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had a good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 µmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). CONCLUSION: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

Nitric oxide-driven nanomotors with bowl-shaped mesoporous silica for targeted thrombolysis.

Vein thrombosis is one of the most serious types of cardiovascular disease. During the traditional treatment, due to the excessive blood flow rate, the drug utilization rate at the thrombus site is low and the thrombolysis efficiency is poor. In this study, bowl-shaped silica nanomotors driven by nitric oxide (NO) are designed to target the thrombus surface by modifying arginine-glycine-aspartic acid (RGD) polypeptide, and simultaneously loading l-arginine (LA) and thrombolytic drug urokinase (UK) in its mesopore structure. LA can react with excessive reactive oxygen species (ROS) in the thrombus microenvironment to produce NO, thus promoting the movement of nanomotors to improve the retention efficiency and utilization rate of drugs in the thrombus site, and at the same time achieve the effect of eliminating ROS and reducing the oxidative stress of inflammatory endothelial cells. The loaded UK can dissolve thrombus quickly. It is worth mentioning that NO can not only be used as a power source of nanomotors, but also can be used as a therapeutic agent to stimulate the growth of endothelial cells and reduce vascular injury. This therapeutic agent based on nanomotor technology is expected to provide support for future research on thrombus treatment.

Electrochemical sensor based on micromotor technology for detection of Ox-LDL in whole blood.

Detecting the concentration of oxidized low-density lipoprotein (Ox-LDL) in whole blood is of great significance for monitoring the development of atherosclerosis. In order to simplify the complex processing steps of blood sample before the detection, an electrochemical sensor based on micromotor technology was designed, which was called magnesium (Mg)-Fe3O4@ prussian blue (PB)@ antibody of Ox-LDL (Ab)@ bovine serum albumin (BSA). The active capture of Ox-LDL in whole blood can be realized by the help of the movement of Mg microsphere with the driving force of H2. Then the captured Ox-LDL was collected on the surface of the magnetic glassy carbon electrode (MGCE) by self-made funnel device, and the content of Ox-LDL was detected by electrochemical workstation in the way of chronoamperometry (i-t). Due to the application of micromotor, the electrochemical sensor proposed in this study had good detection efficiency for Ox-LDL in whole blood with range from 1 × 10-2 µg/mL to 10 µg/mL, and the limit of detection (LOD) towards Ox-LDL was 9.80 × 10-4 µg/mL. The electrochemical sensor based on micromotor technology provides a rapid, effective, and sensitive method for the detection of Ox-LDL in whole blood.