The therapeutic effect of traditional Chinese medicine on breast cancer through modulation of the Wnt/ß-catenin signaling pathway.

Breast cancer, the most prevalent malignant tumor among women globally, is significantly influenced by the Wnt/ß-catenin signaling pathway, which plays a crucial role in its initiation and progression. While conventional chemotherapy, the standard clinical treatment, suffers from significant drawbacks like severe side effects, high toxicity, and limited prognostic efficacy, Traditional Chinese Medicine (TCM) provides a promising alternative. TCM employs a multi-targeted therapeutic approach, which results in fewer side effects and offers a high potential for effective treatment. This paper presents a detailed analysis of the therapeutic impacts of TCM on various subtypes of breast cancer, focusing on its interaction with the Wnt/ß-catenin signaling pathway. Additionally, it explores the effectiveness of both monomeric and compound forms of TCM in the management of breast cancer. We also discuss the potential of establishing biomarkers for breast cancer treatment based on key proteins within the Wnt/ß-catenin signaling pathway. Our aim is to offer new insights into the prevention and treatment of breast cancer and to contribute to the standardization of TCM.

Design, synthesis, and evaluation of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one derivatives: potent BRD4 inhibitors with anti-breast cancer activity.

BRD4 inhibitors have demonstrated promising potential in cancer therapy. However, their therapeutic efficacy in breast cancer varies depending on the breast cancer subtype, particularly in the treatment of TNBC. In this study, we designed and synthesized 94 derivatives of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one to evaluate their inhibitory activities against BRD4. Notably, compound DDT26 exhibited the most potent inhibitory effect on BRD4, with an IC50 value of 0.237 ± 0.093 µM. DDT26 demonstrated significant anti-proliferative activity against both TNBC cell lines and MCF-7 cells. Intriguingly, the phthalazinone moiety of DDT26 mimicked the PAPR1 substrate, resulting in DDT26 displaying a moderate inhibitory effect on PARP1 with an IC50 value of 4.289 ± 1.807 µM. Further, DDT26 was shown to modulate the expression of c-MYC and γ-H2AX, induce DNA damage, inhibit cell migration and colony formation, and arrest the cell cycle at the G1 phase in MCF-7 cells. Our findings present potential lead compounds for the development of potent anti-breast cancer agents targeting BRD4.

The First Discovery of a Microstructure in Black Plaster and Its Performance Characterization.

Background: Black plaster is one of the classic dosage forms of traditional Chinese medicine for external use and has been widely utilized since the Tang and Song Dynasties. In this paper, we take Goupi Gao as the research object and discuss the scientific characteristics of the black plaster dosage form. Goupi Gao ointment is a plaster for external use of traditional Chinese medicine. Methods: Methods for the morphological and quantitative characterization of black plaster's microstructure, based on FESEM-IPP (Field Emission Scanning Electron Microscope IPP Image Processing) technology, were established. According to the actual operating temperature of Goupi Gao, three temperatures were selected: 28°C, 35°C, and 45°C. A UPLC analysis method was applied to the cinnamaldehyde and eugenol in Goupi Gao, and the release behavior of Goupi Gao from three samples at three temperatures was investigated using the paddle over disk method. Preparation of rabbit model of knee osteoarthritis of cold blood stasis type by cold stimulation combined with drug induction. Results: In terms of morphology, Goupi Gao and the blank black plaster matrix both formed a double continuous phase system with a thicker vegetable oil phase and crossed "branched" soap crystal fibers. Based on the IPP image quantification parameters, the pore area (A) was highly positively correlated with temperature. After the 28 °C treatment, A1 = (216.8±59.5) µm2; after the 35 °C treatment, A2 = (259.7±52.8) µm2; after the 45 °C treatment, A3 = (408.0±57.7) µm2, and there were no significant differences in other pore parameters. Conclusion: The black plaster matrix's unique structure makes it highly applicable in numerous medications; it exhibits slow-release and performs well in extreme temperatures, with good adhesion and peeling properties.

Discovery of small molecule ß-catenin suppressors that enhance immunotherapy.

Small molecules directly downregulating ß-catenin could potentially offer a more effective therapeutic approach for combating against cancer stem cells, as compared to targeting the downstream components of the Wnt/ß-catenin pathway. The challenge, however, lies in the fact that very few ß-catenin suppressors have proven clinically effective, leaving a significant gap in medical solutions. Given that E-cadherin has a natural affinity for ß-catenin, it stands to reason that agents designed to increase E-cadherin expression might provide an alternative method of regulating ß-catenin levels. In this study, we report our discovery of DSS-C12 and DSS-B8, specific ester-based drugs derived from Dan-Shen-Su (DSS) extracted from the herb Salvia miltiorrhiza. Remarkably, these compounds display a potent ability to downregulate ß-catenin, while also improving overall survival in post-surgery mice. Additionally, when these drugs are used in combination with PD-L1 checkpoint blockade, they stimulate enhanced systemic immune responses leading to significant suppression of primary tumor growth. In-depth mechanistic studies revealed that DSS-B8 functions as a vitamin D receptor agonist without inducing hypercalcemic effects. Collectively, our findings indicate that DSS-derived small molecules have considerable potential as clinically viable therapeutic strategies for ß-catenin deactivation.

A review of struvite crystallization for nutrient source recovery from wastewater.

Nutrient recovery from wastewater not only reduces the nutrient load on water resources but also alleviates the environmental problems in aquatic ecosystems, which is a solution to achieve a sustainable society. Besides, struvite crystallization technology is considered a potential nutrient recovery technology because the precipitate obtained can be reused as a slow-release fertilizer. This review presents the basic properties of struvite and the theory of the basic crystallization process. In addition, the possible influencing variables of the struvite crystallization process on the recovery efficiency and product purity are also examined in detail. Then, the advanced auxiliary technologies for facilitating the struvite crystallization process are systematically discussed. Moreover, the economic and environmental benefits of the struvite crystallization process for nutrient recovery are introduced. Finally, the shortcomings and inadequacies of struvite crystallization technology are presented, and future research prospects are provided. This work serves as the foundation for the future use of struvite crystallization technology to recover nutrients in response to the increasingly serious environmental problems and resource depletion.

Self-Assembling Anchorage of Hyaluronic Acid on the Nanoparticle Surface Confers Superiority of Triple Negative Breast Cancer Treatment.

Triple-negative breast cancer (TNBC) has been listed as one of the most fatal diseases, and no effective targeting treatment is clinically available. Although CD44-targeting hyaluronic acid (HA) has been utilized as targeting ligands in many studies, no facile ways have been developed through HA self-assembly at the nanoparticle surface. Herein, we reported N-isopropylacrylamide-grafted chitosan-based nanoparticles self-assembling with HA (HA-NPs) through electrostatic forces and loaded with curcumin (CUR). The HA-NPs displayed pH-responsive properties due to the chemical modification of chitosan, and the preparation process was optimized by central composite design-response surface methodology. HA anchorage confers the vehicle with tumor-targeting capability. HA-NPs displayed more robust effects of inhibiting TNBC primary tumor growth than free CUR and a plain counterpart but without increased systemic cytotoxicity. In addition, in vivo pharmacokinetic studies showed that HA-NPs significantly increased the in vivo residence time of free CUR and improved the bioavailability of CUR. These findings suggested that chitosan-based HA-NPs may provide a feasible and unique strategy to achieve CD44 targeting and enhance its efficacy in vivo for the treatment of advanced TNBC.

An emission-free controlled potassium pyrosulfate roasting-assisted leaching process for selective lithium recycling from spent Li-ion batteries.

Recycling critical metals from spent Li-ion batteries (LIBs) is important for the overall sustainability of future batteries. This study reports an improved sulfation roasting technology to efficiently recycle Li and Co from spent LiCoO2 LIBs using potassium pyrosulfate as sulfurizing reagent. By sulfation roasting, LiCoO2 was converted into water-soluble lithium potassium sulfate and water-insoluble cobalt oxide. Under optimal conditions, 98.51% Li was leached in water, with a selectivity of 99.86%. More importantly, sulfur can be recirculated thoroughly, and the sulfur atomic efficiency can be significantly enhanced by controlling the amount of potassium pyrosulfate. Li ions from the water leaching process were recovered by chemical precipitation. Furthermore, application of this technology to other spent LIBs, such as LiMn2O4 and LiNi0.5Co0.2Mn0.3O2, verified its effectiveness for selective recovery Li. These findings can provide some inspiration for high efficiency and environmentally friendly recovery metal from spent LIBs.

Long non-coding RNAs play an important regulatory role in tumorigenesis and tumor progression through aerobic glycolysis.

Compared to normal cells, cancer cells generate ATP mainly through aerobic glycolysis, which promotes tumorigenesis and tumor progression. Long non-coding RNAs (LncRNAs) are a class of transcripts longer than 200 nucleotides with little or without evident protein-encoding function. LncRNAs are involved in the ten hallmarks of cancer, interestingly, they are also closely associated with aerobic glycolysis. However, the mechanism of this process is non-transparent to date. Demonstrating the mechanism of lncRNAs regulating tumorigenesis and tumor progression through aerobic glycolysis is particularly critical for cancer therapy, and may provide novel therapeutic targets or strategies in cancer treatment. In this review, we discuss the role of lncRNAs and aerobic glycolysis in tumorigenesis and tumor progression, and further explore their interaction, in hope to provide a novel therapeutic target for cancer treatment.

Dual-target inhibitors based on PARP1: new trend in the development of anticancer research.

PARP1 is a hot target, and its inhibitors have been approved for cancer therapy. However, some undesirable properties restrict the application of PARP1 inhibitors, including drug resistance, side effects and low efficiency. For multifactorial diseases, dual-target drugs have exhibited excellent synergistic effects, such as reduced drug resistance, low side effects and high therapeutic efficacy, by simultaneously regulating the main pathogenic and compensatory signal pathways of diseases. In recent years, several dual-target inhibitors based on PARP1 have been reported and have demonstrated unique advantages. In this review we summarize the research progress in dual-target inhibitors based on PARP1 and discuss the related drug design strategies and structure-activity relationships. This work is expected to provide references for the development of PARP1 inhibitors.

Expression Profile of Hydroxysteroid Dehydrogenase-like 2 in Polychaete Perinereis aibuhitensis in Response to BPA.

Hydroxysteroid dehydrogenases (HSDs) play an important role in the metabolism of steroids and xenobiotics. However, the function of HSDs in invertebrates is unclear. In this study, we cloned the hydroxysteroid dehydrogenase-like 2 (HSDL2) gene in Perinereis aibuhitensis, which is 1652 bp in length, encoding 400 amino acids. This sequence contains conserved short-chain dehydrogenase and sterol carrier protein-2 domain, and the alignment analysis showed its close relationship with other invertebrate HSDL2. Further, the tissue distribution analysis of the HSDL2 gene showed it is expressed strongly in the intestine. The expression level of HSDL2 after inducement with bisphenol A (BPA) was also detected both at transcriptional and translational levels. The results inferred that BPA exposure can induce HSDL2 expression, and the inductive effect was obvious in the high-concentration BPA group (100 µg/L). In summary, our results showed the detoxification function of HSDL2 in polychaetes.

Stabilization of the Metastable α-Form of Indomethacin Induced by the Addition of 2-Hydroxypropyl-ß-Cyclodextrin, Causing Supersaturation (Spring) and Its Sustaining Deployment (Parachute).

The purpose of this study is to find that a small amount of 2-Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) can produce a parachute effect on indomethacin (INM). From the examination of dissolution curves and concentration after several days, the supersaturation of INM was observed for the mixtures containing HP-ß-CD at a molar ratio ≤ 0.5, and the sustained deployment of supersaturation was found not only in equimolar mixtures but also in mixtures with a shortage of HP-ß-CD. In the solid state, it was compared the physical properties of INM/HP-ß-CD mixtures using two different mixing methods and determined the stoichiometry of INM and HP-ß-CD. Differential scanning calorimetry (DSC) revealed that the polymorphs of INM were converted by HP-ß-CD into an amorphous state. Furthermore, X-ray powder diffraction (XRPD) and DSC-XRPD demonstrated that INM crystals from the INM/HP-ß-CD mixture prepared from an EtOH solution were metastable. In conclusion, these phenomena may be considered the "spring" and "parachute" effects of mixtures with a shortage of HP-ß-CD, as they depended on the presence of the metastable α-form of INM. The addition of 1/3 to 1/20 equivalents of HP-ß-CD to INM enhanced INM solubility.

Breast cancer stem cells, heterogeneity, targeting therapies and therapeutic implications.

Both hereditary and sporadic breast cancer are suggested to develop from a stem cell subcomponent retaining most key stem cell properties but with dysregulation of self-renewal pathways, which drives tumorigenic differentiation and cellular heterogeneity. Cancer stem cells (CSCs), characterized by their self-renewal and differentiation potential, have been reported to contribute to chemo-/radio-resistance and tumor initiation and to be the main reason for the failure of current therapies in breast cancer and other CSC-bearing cancers. Thus, CSC-targeted therapies, such as those inducing CSC apoptosis and differentiation, inhibiting CSC self-renewal and division, and targeting the CSC niche to combat CSC activity, are needed and may become an important component of multimodal treatment. To date, the understanding of breast cancer has been extended by advances in CSC biology, providing more accurate prognostic and predictive information upon diagnosis. Recent improvements have enhanced the prospect of targeting breast cancer stem cells (BCSCs), which has shown promise for increasing the breast cancer remission rate. However, targeted therapy for breast cancer remains challenging due to tumor heterogeneity. One major challenge is determining the CSC properties that can be exploited as therapeutic targets. Another challenge is identifying suitable BCSC biomarkers to assess the efficacy of novel BCSC-targeted therapies. This review focuses mainly on the characteristics of BCSCs and the roles of BCSCs in the formation, maintenance and recurrence of breast cancer; self-renewal signaling pathways in BCSCs; the BCSC microenvironment; potential therapeutic targets related to BCSCs; and current therapies and clinical trials targeting BCSCs.

The first complete chloroplast genome of Hovenia acerba Lindl.

Hovenia acerba Lindl. is an important medicinal plant, for which complete chloroplast genome (Accession: MN782301) was sequenced, assembled and annotated. The genome size is 161,668 bp and the overall GC content is 36.69%, with large single-copy (LSC, 89,451bp) regions, small single-copy (SSC, 18,979 bp) regions, and two inverted repeat regions (IRs, 26,619 bp each). A total of 130 genes are successfully annotated, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic relationships showed that H. acerba is closely related to the species of Ziziphus genus.

History of uses, phytochemistry, pharmacological activities, quality control and toxicity of the root of Stephania tetrandra S. Moore: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: the root of Stephania tetrandra S. Moore, known as Fangji in China (Chinese: ), is a traditional Chinese medicine (TCM) with a long history of use. Fangji is a type of medicine used to treat various diseases, including rheumatism, arthralgia, edema and beriberi, unfavorable urination, and eczema. AIM OF THIS REVIEW: There are many newly published reports on the history of uses, phytochemistry, pharmacological activity, quality control and toxicity of Fangji; however, no comprehensive systematic review exists. Therefore, the purpose of this review is to compile the latest and most comprehensive information on Fangji and provide a scientific basis for future research. MATERIALS AND METHODS: A systematic literature search was conducted using multiple electronic databases, including SciFinder, Web of Science, PubMed, Science Direct, ACS Publications, J-stage, SpringerLink, Thieme, Wiley, and CNKI. Information was also collected from journals and Chinese Pharmacopoeia. RESULT: Thus far, there were uses of Fangji against 20 different diseases/disorders, such as relieving edema and rheumatism pain, treating cough and asthma, treating enuresis, astringent urine and beriberi edema, purging blood and damp heat, and dispelling wind evil and dampness, etc. 48 compounds have been isolated from Fangji, belonging to alkaloids, flavonoids, and steroids, other compounds. The crude extracts and isolated compound of Fangji have shown a wide range of pharmacological activities, such as anti-tumor, anti-inflammatory, and neuroprotective activities, as well as role in reoxygenation, and antimicrobial effect, etc. Moreover, qualitative and quantitative analyses of quality control are reviewed, including qualitative analyses for the identification of compounds, as well as fingerprint and quantitative analyses by high performance liquid chromatography (HPLC) and capillary electrochromatography (CE). In the toxicity study, the hepatotoxicity, hepatorenal toxicity, nephrotoxicity, subacute and acute toxicities of the alcohol extract and water extract of Fangji, and tetrandrine were studied in-vitro and in-vivo experiments. CONCLUSION: In the history of uses, Fangji can be used to treat a variety of diseases, most of which are manifested in removing wind and dampness. In recent years, the phytochemistry of Fangji has rarely been reported. The pharmacological activities of Fangji mainly focus on the compounds, tetrandrine and fangchinoline, and there are a few reports on the pharmacological studies of other compounds in Fangji. Moreover, the quality control of Fangji lacks a standard fingerprint to distinguish Fangji from other easily-confused medicinal materials. In the toxicity study, there is no report on the mechanism of toxicity research. Therefore, further studies on such mechanisms are needed.

Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals.

Cyclodextrins (CDs) form complex crystals with drugs and improve physicochemical properties of drugs. However, only few reports have summarized relationships between crystal structures of drug/CD and dissolution behavior. In this study, we developed cimetidine (CIM)/CD complex crystals to achieve sustained drug release and investigated the relationship between the dissolution behavior of CIM/CD complexes and their crystal structures. CIM and 3 types of CDs (α-, ß-, and γ-CD) formed a complex crystal when subjected to solvent mixing. The CIM/CD complexes had a highly reduced dissolution rate compared to that of the physical mixture of CIM and CD. ß-CD improved the solubility of CIM, whereas γ-CD decreased its solubility. Based on the phase solubility diagram, CIM and α-, ß-, and γ-CD indicated A-type positive (AP) and AL deviation, and B-type limited solubility (BS) profiles, respectively. In γ-CD, the saturated concentration of CIM decreased owing to the formation of a low-solubility complex with CIM. CIM/α-CD formed cage-type crystals, and CIM/ß-CD and CIM/γ-CD formed channel-type crystals. The dissolution rate constant (k) of CIM/α-CD and CIM/ß-CD were 0.045 and 0.04 h-1, respectively. CIM/γ-CD and CIM/ß-CD displayed channel-type crystals; however, the channel-type crystals of CIM/γ-CD were stabilized by the presence of additional water molecules.

A study of nanometre aggregates formation mechanism and antipyretic effect in Bai-Hu-Tang, an ancient Chinese herbal decoction.

BACKGROUND: Bai-Hu-Tang (BHT), a Chinese herbal decoction used as an antipyretic agent, results from the combination of Anemarrhena asphodeloides Bunge, Glycyrrhizae, Japonica rice, and Gypsum. In our previous study, we identified nanoaggregates in BHT. However, the present study aimed to analyze and elucidate the mechanism of nanoaggregate formation and to investigate its antipyretic effect. METHODS: A BHT decoction extract was split into 15 groups, and in each group, the extract was further separated into two solutions: Nano-phase and Decoction. The physicochemical properties of these solutions, such as particle size, salinity, conductivity, and surface tension were investigated, and analyzed the 15 groups of by transmission electron microscopy (TEM) and fingerprint chromatography. Furthermore, the antipyretic effect of nanoaggregates was evaluated through enzyme-linked immunosorbent assays, HE staining, Western Blot, and Real-time PCR. RESULTS: In the 15 groups, the salinity and conductivity results showed a promoting and stabilizing effect towards the Nano-phase formation. Analysis of the surface tension indicated good solubilization of Radix Glycyrrhizae. The TEM analysis of the BHT separated extracts revealed that only in the presence of Japonica rice the Nano-phase is formed. Sixteen common peaks were identified in the BHT fingerprint chromatogram, and the main chemical components were Neomangiferin, Mangiferin, Liquiritin, and Ammonium glycyrrhizinate. Furthermore, BHT and nanoaggregates from Bai-Hu-Tang (N-BHT) groups did not differ in the main chemical components. Additionally, the N-BHT group had the same antipyretic effect compared with the BHT group. However, the pathological analysis indicated that treatment with N-BHT could ameliorate the lung damage in the rat. At the same time, N-BHT group inhibited expression of several proteins, specifically IL-1ß, TRPV4, NF-κB, and TNF-α, which agreed with the Real-time PCR results. CONCLUSION: We identified the key factors that are involved in the nano-phase formation. Also, by Western blot and Real-time PCR methods, we investigated the N-BHT mechanism of antipyretic action. The discovery of the N-BHT formation would provide a new idea of studying traditional Chinese medicine decoction.

An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression.

Objectives: To evaluate the pharmacodynamical effects and pharmacological mechanism of Ginsenoside H dripping pills (GH) in chronic unpredictable mild stress (CUMS) model rats. Methods: First, the CUMS-induced rat model was established to assess the anti-depressant effects of GH (28, 56, and 112 mg/kg) by the changes of the behavioral indexes (sucrose preference, crossing score, rearing score) and biochemical indexes (serotonin, dopamine, norepinephrine) in Hippocampus. Then, the components of GH were identified by ultra-performance liquid chromatography-iron trap-time of flight-mass spectrometry (UPLC/IT-TOF MS). After network pharmacology analysis, the active ingredients of GH were further screened out based on OB and DL, and the PPI network of putative targets of active ingredients of GH and depression candidate targets was established based on STRING database. The PPI network was analyzed topologically to obtain key targets, so as to predict the potential pharmacological mechanism of GH acting on depression. Finally, some major target proteins involved in the predictive signaling pathway were validated experimentally. Results: The establishment of CUMS depression model was successful and GH has antidepressant effects, and the middle dose of GH (56 mg/kg) showed the best inhibitory effects on rats with depressant-like behavior induced by CUMS. Twenty-eight chemical components of GH were identified by UPLC/IT-TOF MS. Subsequently, 20(S)-ginsenoside Rh2 was selected as active ingredient and the PPI network of the 43 putative targets of 20(S)-ginsenoside Rh2 containing in GH and the 230 depression candidate targets, was established based on STRING database, and 47 major targets were extracted. Further network pharmacological analysis indicated that the cAMP signaling pathway may be potential pharmacological mechanism regulated by GH acting on depression. Among the cAMP signaling pathway, the major target proteins, namely, cAMP, PKA, CREB, p-CREB, BDNF, were used to verify in the CUMS model rats. The results showed that GH could activate the cAMP-PKA-CREB-BDNF signaling pathway to exert antidepressant effects. Conclusions: An integrative pharmacology-based pattern was used to uncover that GH could increase the contents of DA, NE and 5-HT, activate cAMP-PKA-CREB-BDNF signaling pathway exert antidepressant effects.

A high-throughput and untargeted lipidomics approach reveals new mechanistic insight and the effects of salvianolic acid B on the metabolic profiles in coronary heart disease rats using ultra-performance liquid chromatography with mass spectrometry.

High-throughput lipidomics provides the possibility for the development of new therapeutic drugs. Accordingly, herein, we reveal the protective role of salvianolic acid B (Sal B) in rats with coronary heart disease (CHD) and propose a new mechanism for its action through a high-throughput and non-targeted lipidomics strategy. A CHD animal model was induced by consecutive high-fat diet feeding with vitamin D3 injection. At the end of the 8th week, the serum sample was analyzed to explore the metabolic biomarker and pathway changes using untargeted lipidomics based on ultra-performance liquid chromatography with mass spectrometry (UPLC/MS). In addition, blood and heart tissue samples were collected and processed for the detection of biochemical indicators and liver histological observation. After salvianolic acid B treatment, the levels of LDH, CK, CK-MB, MYO, CTn1, TG, TC, LDL-c, and Apo(b) were significantly lower than that in the model group, while the levels of HDL-c and Apo(a1) were significantly higher than that in the model group. Furthermore, the histological features of fibrosis and steatosis were also evidently relieved in the model group. A total of twenty-six potential biomarkers were identified to express the lipid metabolic turbulence in the CHD animal models, of which twenty-two were regulated by salvianolic acid B trending to the normal state, including TG(20:0/20:4/o-18:0), PC(20:4/18:1(9Z)), PC(18:3/20:2), PA(18:0/18:2), LysoPE(18:2/0:0), SM(d18:0/22:1), PE(22:6/0:0), LysoPE (20:4/0:0), sphinganine, Cer(d18:0/18:0), PS(14:0/14:1), PC (18:0/16:0), LysoPC(17:0), PE(22:2/20:1), PC(20:3/20:4), PE(20:4/P-16:0), PS(20:3/18:0), cholesterol sulfate, TG(15:0/22:6/18:1), prostaglandin E2, arachidonic acid and sphingosine-1-phosphate. According to the metabolite enrichment and pathway analyses, the pharmacological activity of salvianolic acid B on CHD is mainly involved in three vital metabolic pathways including glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism. Thus, based on the lipidomics-guided biochemical analysis of the lipid biomarkers and pathways, Sal B protects against CHD with good therapeutic effect by regulating glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism, inhibiting oxidative stress damage and lipid peroxidation.

Strategy for chemotherapeutic delivery using a nanosized porous metal-organic framework with a central composite design.

BACKGROUND: Enhancing drug delivery is an ongoing endeavor in pharmaceutics, especially when the efficacy of chemotherapy for cancer is concerned. In this study, we prepared and evaluated nanosized HKUST-1 (nanoHKUST-1), nanosized metal-organic drug delivery framework, loaded with 5-fluorouracil (5-FU) for potential use in cancer treatment. MATERIALS AND METHODS: NanoHKUST-1 was prepared by reacting copper (II) acetate [Cu(OAc)2] and benzene-1,3,5-tricarboxylic acid (H3BTC) with benzoic acid (C6H5COOH) at room temperature (23.7°C±2.4°C). A central composite design was used to optimize 5-FU-loaded nanoHKUST-1. Contact time, ethanol concentration, and 5-FU:material ratios were the independent variables, and the entrapment efficiency of 5-FU was the response parameter measured. Powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption were used to determine the morphology of nanoHKUST-1. In addition, 5-FU release studies were conducted, and the in vitro cytotoxicity was evaluated. RESULTS: Entrapment efficiency and drug loading were 9.96% and 40.22%, respectively, while the small-angle X-ray diffraction patterns confirmed a regular porous structure. The SEM and TEM images of the nanoHKUST-1 confirmed the presence of round particles (diameter: approximately 100 nm) and regular polygon arrays of mesoporous channels of approximately 2-5 nm. The half-maximal lethal concentration (LC50) of the 5-FU-loaded nanoHKUST-1 was approximately 10 µg/mL. CONCLUSION: The results indicated that nanoHKUST-1 is a potential vector worth developing as a cancer chemotherapeutic drug delivery system.

[Liposome modified with VIP-lipopeptide as a new drug delivery system].

We have designed a novel lipid analog (lipopeptide) that mimics the structural features of modified phospholipids. This lipopeptide is easily synthesized using a peptide synthesizer and has been shown to be useful for the modification of liposomes, which are used as an active targeted drug delivery system (DDS). Vasoactive intestinal peptide (VIP) has high homology with pituitary adenylate cyclase activating peptide (PACAP). There are three major PACAP receptors: PAC1R, VPAC1R, and VPAC2R. PAC1R has affinity only for PACAP, whereas VPAC1R and VPAC2R have the same affinity for both VIP and PACAP. In the present study, we synthesized several lipopeptides conjugated with VIP through different linkers and found that liposomes modified with these lipopeptides (VIP-Lips) selectively recognized the PACAP/VIP receptors. The anti-cancer activity of these VIP-Lips was evaluated by encapsulation of an antitumor drug, doxorubicin (DOX), into the modified liposomes (VIP-Lips-DOX) against the human osteosarcoma cell line, Saos-2, which highly expresses the VIP receptor. cAMP production was then measured to determine how well the VIP-Lips were able to recognize VPAC2R. The results clearly indicate that the proposed lipopeptide methodology holds promise as a DDS for cancer therapy.