Novel Multifunctional Silver Nanocomposite Serves as a Resistance-Reversal Agent to Synergistically Combat Carbapenem-Resistant Acinetobacter baumannii.

In the face of the abundant production of various types of carbapenemases, the antibacterial efficiency of imipenem, seen as "the last line of defense", is weakening. Following, the incidence of carbapenem-resistant Acinetobacter baumannii (CRAB), which can generate antibiotic-resistant biofilms, is increasing. Based on the superior antimicrobial activity of silver nanoparticles against multifarious bacterial strains compared with common antibiotics, we constructed the IPM@AgNPs-PEG-NOTA nanocomposite (silver nanoparticles were coated with SH-PEG-NOTA as well as loaded by imipenem) whose core was a silver nanoparticle to address the current challenge, and IPM@AgNPs-PEG-NOTA was able to function as a novel smart pH-sensitive nanodrug system. Synergistic bactericidal effects of silver nanoparticles and imipenem as well as drug-resistance reversal via protection of the ß-ring of carbapenem due to AgNPs-PEG-NOTA were observed; thus, this nanocomposite confers multiple advantages for efficient antibacterial activity. Additionally, IPM@AgNPs-PEG-NOTA not only offers immune regulation and accelerates tissue repair to improve therapeutic efficacy in vivo but also can prevent the interaction of pathogens and hosts. Compared with free imipenem or silver nanoparticles, this platform significantly enhanced antibacterial efficiency while increasing reactive oxygen species (ROS) production and membrane damage, as well as affecting cell wall formation and metabolic pathways. According to the results of crystal violet staining, LIVE/DEAD backlight bacterial viability staining, and real-time quantitative polymerase chain reaction (RT-qPCR), this silver nanocomposite downregulated the levels of ompA expression to prevent formation of biofilms. In summary, this research demonstrated that the IPM@AgNPs-PEG-NOTA nanocomposite is a promising antibacterial agent of security, pH sensitivity, and high efficiency in reversing resistance and synergistically combatting carbapenem-resistant A. baumannii. In the future, various embellishments and selected loads for silver nanoparticles will be the focus of research in the domains of medicine and nanotechnology.

Construction of homologous cancer cell membrane camouflage in a nano-drug delivery system for the treatment of lymphoma.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. RESULTS: Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. CONCLUSIONS: Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.

A Nano-Traditional Chinese Medicine Against Lymphoma That Regulates the Level of Reactive Oxygen Species.

Jolkinolide B (JB) is a bioactive compound isolated from a Chinese herbal medicine that exerts antitumor activity. However, the anti-lymphoma effect of JB and its mechanism are yet to be revealed. Because free JB has poor pharmacokinetics and weak antitumor efficacy, we opted to use black phosphorus quantum dot (BPQD) nanomaterials as a drug loading platform to synthesize a nano-traditional Chinese medicine (nano-TCM) called BPQDs@JB. Compared with free JB, Raji cells administrated with BPQDs@JB exhibited the cell viability of 19.85 ± 1.02%, and the production of intracellular reactive oxygen species (ROS) was promoted. Likewise, BPQDs@JB was capable of rising the apoptosis rate of Raji cells to 34.98 ± 1.76%. In nude mice transplanted tumor model administrated with BPQDs@JB, the tumor tissue sections administrated with BPQDS@JB achieved a conspicuous red fluorescence, demonstrating the presence of most ROS production in the BPQDS@JB. TUNEL achieved a number of positive (brown) nuclei in vivo, revealing that BPQDS@JB could significantly induce tumor tissue apoptosis. As revealed from the mentioned results, BPQDs@JB can generate considerable ROS and interfere with the redox state to inhibit tumor. In brief, BPQDs@JB may be adopted as a treatment option for lymphoma.

Platelet-Membrane-Camouflaged Black Phosphorus Quantum Dots Enhance Anticancer Effect Mediated by Apoptosis and Autophagy.

Hederagenin (HED) has poor anticancer activity whose mechanism remains unclear and unsystematic. Free drugs for cancer treatment exhibit disadvantages such as poor targeting and efficacy. To address this problem, we constructed a nanoplatform of black phosphorus quantum dots (BPQDs) camouflaged with a platelet membrane (PLTm) carrying HED, termed PLT@BPQDs-HED. PLTm vesicles serve as a shell to encapsulate multiple high-efficiency drug-loaded nanocores, which can target tumor sites and significantly improve antitumor activity. Compared with free HED, this platform significantly reduced tumor cell viability and the mitochondrial membrane potential (MMP), while increasing the production of intracellular reactive oxygen species (ROS). The platform also significantly increased the amounts of terminal deoxyribonucleotide transferase mediated dUTP nick-end-labeling (TUNEL)-positive cells and decreased the number of Ki-67-positive cells. In addition, the platform upregulated proapoptotic factor Bax, downregulated the anti-apoptotic molecule Bcl-2, activated Caspase-9 and Caspase-3, and stimulated Cytochrome C release. Moreover, the platform promoted the formation of autophagosomes, upregulated Beclin-1, and promoted LC3-I conversion into LC3-II. This study demonstrated that the above platform significantly enhances tumor targeting and promotes mitochondria-mediated cell apoptosis and autophagy in tumor cells.

Anti-tumour effects of red blood cell membrane-camouflaged black phosphorous quantum dots combined with chemotherapy and anti-inflammatory therapy.

Conventional anti-tumour chemotherapy is facing the challenges of poor specificity, high toxicity and drug resistance. Tumour microenvironment (TME) plays a critical role in tumour development and drug resistance. To address this problem, we constructed a novel anti-tumour nanoparticle platform RBC@BPQDs-DOX/KIR, black phosphorus nanoparticle quantum dots (BPQDs) with one of the chemotherapeutics (doxorubicin, DOX) and an anti-inflammatory traditional Chinese medicine active component (Kirenol, KIR). Red blood cell membrane (RBCm) vesicles were used as the shell to envelop several nanocores. The combination of DOX and KIR may promote therapeutic efficacy, at which the anti-apoptotic effect of the tumour cells was inhibited (by downregulating Bcl-2 and upregulating Bax) and the tumour progression-related inflammatory factors, such as tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) were downregulated. Furthermore, TME was remodelled and the anti-tumour effect of DOX was magnified. RBCm imparts high biocompatibility and enhanced permeability and retention (EPR) effects to RBC@BPQDs-DOX/KIR, thus enhancing its tumour passively targetability. Overall, the RBCm-camouflaged drug delivery system RBC@BPQDs-DOX/KIR as a promising therapy for targeted chemotherapeutics and anti-inflammatory therapeutics may provide a specific and highly efficient anti-tumour treatment choice.

Anti-inflammatory effects of hederagenin on diabetic cardiomyopathy via inhibiting NF-κB and Smads signaling pathways in a type-2 diabetic mice model.

Hederagenin (HED) is a bioactive natural compound of pentacyclic triterpenes extracted from many medicinal plants. It has a wide range of antitumor cytotoxic effects and significant anti-inflammation effects. However, at present, it is unclear whether HED can inhibit cardiac remodelling caused by diabetic cardiomyopathy. In this study, we evaluated the effects of HED on pathological abnormalities in cardiac structures and cardiac insufficiency caused by diabetic cardiomyopathy and focused on the inflammatory signalling pathways of the diabetic heart. Treatment with HED reduced pro-inflammatory cytokines, the heart and body mass of diabetic db/db mice but had no effect on fasting plasma glucose (FPG). Moreover, after HED treatment, the cardiac dysfunction of diabetic mice was relieved, and myocardial hypertrophy and fibrosis decreased. Furthermore, HED inhibited the nuclear translocation of nuclear factor-κB (NF-κB) and Smads and decreased the transcriptional activity of NF-κB and Smads. Additionally, the expression levels of transforming growth factor (TGF)-ß1 and collagen I, which are target downstream molecules of the NF-κB and Smads signalling pathways, were also decreased in diabetic hearts. Taken together, our findings suggest that the cardioprotective effect of HED may be achieved by reducing the activation of inflammation-associated NF-κB and Smads signalling. We suggest that the protective effect of HED on the diabetic heart, as revealed in this study, should be further explored in-depth to elucidate its cell biology and molecular mechanisms.

Flavonoids isolated from Sinopodophylli Fructus and their bioactivities against human breast cancer cells.

Four prenylated flavonoids compounds 1-4, named sinopodophyllines A-D, and a flavonoid glycoside (compound 13), sinopodophylliside A, together with 19 known compounds (compounds 5-12 and 14-24) were isolated from the fruits of Sinopodophyllum hexandrum. The structures of new compounds were elucidated by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compounds 1-6, 9-11, and 14-17 were tested for their cytotoxicity against human breast-cancer T47D, MCF-7 and MDA-MB-231 cells in vitro, and compounds 2, 5, 6, 10 and 11 showed significant cytotoxicity (IC50 values < 10 µmol·L-1) against T47D cells.

Naturally Occurring Cinnamic Acid Sugar Ester Derivatives.

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3',6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM), presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae. This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds.

[The efficacy and safety of autologous cryopreserved platelet transfusion in management of thrombocytopenia after chemotherapy in hematological malignancy].

OBJECTIVE: To investigate the efficacy and safety of autologous cryopreserved platelet transfusion in the management of thrombocytopenia after chemotherapy in hematological malignancy. METHODS: A total of 40 patients diagnosed as hematological malignancy with complete remission were equally assigned into study group and control group. During chemotherapy interval in the study group, when platelet counts exceeded 120 × 10(9)/L, autologous platelets were collected with CS3000 Cell Separator and cryopreserved at -80°C with 5% dimethylsulfoxide. When platelet counts dropped below 15 × 10(9)/L after chemotherapy, autologous platelets were thawed with 40°C water bath and transfused back to each patient. In the control group, when platelet counts dropped below 15 × 10(9)/L after chemotherapy, allogeneic fresh platelets were transfused. Median loss during the freeze-thaw-wash procedure in study group was observed, and the 1 h, 24 h corrected count increments (CCI) were calculated in the both groups. The hemostatic effects and adverse reactions were also observed. RESULTS: In the control group, 1hCCI and 24h CCI were (19.3 ± 6.1) × 10(9)/L and (12.2 ± 7.0) × 10(9)/L, respectively, with the effective rate of 80% and the transfusion reaction rate of 45%. Totally 20 collection and transfusions were finished in the study group. A total of (3.4 - 8.5) × 10(11) platelet were obtained in each collection. Platelet recovery after freezing and thawing was (73.51 ± 9.03)% (62% - 83%). 1hCCI was (17.4 ± 7.6) × 10(9)/L, 24h CCI was (10.5 ± 5.8) × 10(9)/L and the effective rate was 85%. There was no significant different between the two groups (P > 0.05). The transfusion reaction rate was 15%, which was significantly lower than that of the control group (P < 0.05). Meanwhile, adverse reactions were occurred less in the study group. CONCLUSION: This study demonstrates that autologous cryopreserved platelet transfusions can be safely administered for supporting thrombocytopenia in hematological malignancy patients undergoing chemotherapy.