Consensus holistic virtual screening for drug discovery: a novel machine learning model approach.

In drug discovery, virtual screening is crucial for identifying potential hit compounds. This study aims to present a novel pipeline that employs machine learning models that amalgamates various conventional screening methods. A diverse array of protein targets was selected, and their corresponding datasets were subjected to active/decoy distribution analysis prior to scoring using four distinct methods: QSAR, Pharmacophore, docking, and 2D shape similarity, which were ultimately integrated into a single consensus score. The fine-tuned machine learning models were ranked using the novel formula "w_new", consensus scores were calculated, and an enrichment study was performed for each target. Distinctively, consensus scoring outperformed other methods in specific protein targets such as PPARG and DPP4, achieving AUC values of 0.90 and 0.84, respectively. Remarkably, this approach consistently prioritized compounds with higher experimental PIC50 values compared to all other screening methodologies. Moreover, the models demonstrated a range of moderate to high performance in terms of R2 values during external validation. In conclusion, this novel workflow consistently delivered superior results, emphasizing the significance of a holistic approach in drug discovery, where both quantitative metrics and active enrichment play pivotal roles in identifying the best virtual screening methodology.Scientific contributionWe presented a novel consensus scoring workflow in virtual screening, merging diverse methods for enhanced compound selection. We also introduced 'w_new', a groundbreaking metric that intricately refines machine learning model rankings by weighing various model-specific parameters, revolutionizing their efficacy in drug discovery in addition to other domains.

The role of Tetraspanins in digestive system tumor development: update and emerging evidence.

Digestive system malignancies, including cancers of the esophagus, pancreas, stomach, liver, and colorectum, are the leading causes of cancer-related deaths worldwide due to their high morbidity and poor prognosis. The lack of effective early diagnosis methods is a significant factor contributing to the poor prognosis for these malignancies. Tetraspanins (Tspans) are a superfamily of 4-transmembrane proteins (TM4SF), classified as low-molecular-weight glycoproteins, with 33 Tspan family members identified in humans to date. They interact with other membrane proteins or TM4SF members to form a functional platform on the cytoplasmic membrane called Tspan-enriched microdomain and serve multiple functions including cell adhesion, migration, propagation and signal transduction. In this review, we summarize the various roles of Tspans in the progression of digestive system tumors and the underlying molecular mechanisms in recent years. Generally, the expression of CD9, CD151, Tspan1, Tspan5, Tspan8, Tspan12, Tspan15, and Tspan31 are upregulated, facilitating the migration and invasion of digestive system cancer cells. Conversely, Tspan7, CD82, CD63, Tspan7, and Tspan9 are downregulated, suppressing digestive system tumor cell metastasis. Furthermore, the connection between Tspans and the metastasis of malignant bone tumors is reviewed. We also summarize the potential role of Tspans as novel immunotherapy targets and as an approach to overcome drug resistance. Finally, we discuss the potential clinical value and therapeutic targets of Tspans in the treatments of digestive system malignancies and provide some guidance for future research.

Multimorphological Remoldable Silver Nanomaterials from Multimode and Multianalyte Colorimetric Sensing to Molecular Information Technology.

Inspired by life's interaction networks, ongoing efforts are to increase complexity and responsiveness of multicomponent interactions in the system for sensing, programmable control, or information processing. Although exquisite preparation of single uniform-morphology nanomaterials has been extremely explored, the potential value of facile and one-pot preparation of multimorphology nanomaterials has been seriously ignored. Here, multimorphological silver nanomaterials (M-AgN) prepared by one pot can form interaction networks with various analytes, which can be successfully realized from multimode and multianalyte colorimetric sensing to molecular information technology (logic computing and security). The interaction of M-AgN with multianalytes not only induces multisignal responses (including color, absorbance, and wavelength shift) for sensing metal ions (Cr3+, Hg2+, and Ni2+) but also can controllably reshape its four morphologies (nanodots, nanoparticles, nanorods, and nanotriangles). By abstracting binary relationships between analytes and response signals, multicoding parallel logic operations (including simple logic gates and cascaded circuits) can be performed. In addition, taking advantage of natural concealment and molecular response characteristics of M-AgN nanosystems can also realize molecular information encoding, encryption, and hiding. This research not only promotes the construction and application of multinano interaction systems based on multimorphology and multicomponent nanoset but also provides a new imagination for the integration of sensing, logic, and informatization.

Sequential-Dependent Synthesis of Bimetallic Silver-Chromium Nanoparticles for Multichannel Sensing, Logic Computing, and 3 in 1 Information Protection.

Bimetallic nanomaterials (BNMs) have been used in sensing, biomedicine, and environmental remediation, but their multipurpose and comprehensive applications in molecular logic computing and information security protection have received little attention. Herein, This synthesis method is achieved by sequentially adding reactants under ice bath conditions. Interestingly, Ag-Cr NPs can dynamically selectively sense anions and reductants in multiple channels. Especially, ClO- can be quantitatively detected by oxidizing Ag-Cr NPs with detection limits of 98.37 nM (at 270 nm) and 31.83 nM (at 394 nm). Based on sequential-dependent synthesis process of Ag-Cr NPs, Boolean logic gates and customizable molecular keypad locks are constructed by setting the reactants as the inputs, the states of the resulting solutions as the outputs. Furthermore, dynamically selective response patterns of the Ag-Cr NPs can be converted into binary strings to exploit molecular crypto-steganography to encode, store, and hide information. By integrating the three dimensions of authorization, encryption, and steganography, 3 in 1 advanced information protection based on Ag-Cr nanosensing system can be achieved, which can enhance the anti-cracking ability of information. This research will promote the development and application of nanocomposites in the field of information security and deepen the connection between molecular sensing and the information world.

Highly Efficient Wavelength-Tunable Circularly Polarized Luminescence Film Constructed by Responsive Chiral Aggregation-induced Emission Luminophore.

Key Lab of Environment-friendly Chemistry and Circularly polarized luminescent (CPL) materials with multitudinous inherent advantages shows extensive application. In this work, we prepare a kind of highly efficient wavelength-tunable CPL free-standing films by responsive chiral aggregation-induced emission mesogen. Firstly, the pyridine-functionalized tetraphenylethene monomer (MPy) is designed and synthesized. Then, the different ration of the monomer MPy mixed with the liquid crystal (LC) reactive monomer (LC242) to fabricate a free-standing film by photopolymerization. The obtained film presents efficient CPL with a constant luminescence asymmetry factor (glum ) of +0.75, as well as sensitive wavelength tunability. Finally, this wavelength-tunable CPL film with both fluorescence and CPL modes is successfully applied in anti-counterfeiting and information encryption. This work provides a simple way to construct CPL apparatus with adjustable luminescence wavelength and high glum .

Colorimetric multi-channel sensing of metal ions and advanced molecular information protection based on fish scale-derived carbon nanoparticles.

Some nanosystems based on carbon nanomaterials have been used for fluorescent chemical/biosensing, elementary information processing, and textual coding. However, little attention has been paid to utilizing biowaste-derived carbon nanomaterials for colorimetric multi-channel sensing and advanced molecular information protection (including text and pattern information). Herein, fish scale-derived carbon nanoparticles (FSCN) were prepared and used for colorimetric detection of metal ions, encoding, encrypting and hiding text- and pattern-based information. The morphology and composition of FSCN were analyzed by TEM, XRD, FTIR, and XPS, and it was found that the FSCN-based multi-channel colorimetric sensing system can detect Cr6+ (detection limit of 56.59 nM and 13.32 nM) and Fe3+ (detection limit of 81.55 nM) through the changes of absorption intensity at different wavelengths (272, 370, and 310 nm). Moreover, the selective responses of FSCN to 20 kinds of metal ions can be abstracted into a series of binary strings, which can encode, hide, and encrypt traditional text-based and even two-dimensional pattern-based information. The preparation of carbon nanomaterials derived from waste fish scales can stimulate other researcheres' enthusiasm for the development and utilization of wastes and promoting resource recycling. Inspired by this work, more researches will continue to explore the world of molecular information technology.

A molecular paradigm: "Plug-and-play" chemical sensing and crypto-steganography based on molecular recognition and selective response.

Inspired by information processing and communication in nature based on molecular recognition and structural diversity, ongoing efforts aim to development of artificial molecular or nano-systems for sensing, logic computing, and even data storage and safety. However, due to their preparation/functionalization shortcomings (laborious and time-consuming), poor flexibility and compatibility, and limited paradigm, it is still a big challenge whether simple molecules can be used to achieve comprehensive and universal applications from sensing to information storage and protection. Herein, we for the first time demonstrated a molecular paradigm-computer-like "basic input output system (BIOS)" which can realize "plug-and-play" sensing, information encoding, molecular cryptography, and steganography based on a simple artificial molecule (p-nitrophenol, PNP). Based on its molecular recognition and inherent chemical identities, PNP was utilized for colorimetric detection of multiple metal ions (Hg2+, Fe3+, Al3+, Cr3+) and distinguishing their valence (like Cr3+/Cr6+, Fe3+/Fe2+). Interestingly, PNP can achieve the "plug-and-play" fluorescent expansion of detection channels by directly mixing with fluorescent molecules, indicating that PNP molecule can be served as a molecular BIOS with flexibility and compatibility. Impressively, the selectivity embedded in PNP-based BIOS sensing system can be developed as molecular-level double cryptographic steganography to encode, encrypt and hide specific information (like the content of classical literature). This research not only provides a basic idea for building a molecular paradigm with "plug-and-play" flexibility and compatibility, but also provides ideas for the use of molecular sensing and informatization to open up the digitalization of the molecular world.

Microwave-Assisted Synthesis of Silver Nanoparticles for Multimode Colorimetric Sensing of Multiplex Metal Ions and Molecular Informatization Applications.

Plasmonic materials have been widely used in chemo/biosensing and biomedicine. However, little attention has been paid to the application of plasmonic materials in terms of the transition from molecular sensing to molecular informatization. Herein, we demonstrated that silver nanoparticles (AgNPs) prepared through facile and rapid microwave heating have multimode colorimetric sensing capabilities to different metal ions (Cr3+, Hg2+, and Ni2+), which can be further transformed into interesting and powerful molecular information technology (massively parallel molecular logic computing and molecular information protection). The prepared AgNPs can quantitatively and sensitively detect Cr3+ and Hg2+ in actual water samples. The AgNPs' multimode-guided multianalyte sensing processing was further investigated to construct a series of basic logic gates and advanced cascaded logic circuits by considering the analytes as the inputs and the colorimetric signals (like color, absorbance, wavelength shift) as the outputs. Moreover, the selective responses and molecular logic computing ability of AgNPs were also utilized to develop molecular cryptosteganography for encrypting and hiding some specific information, which proves that the molecular world and the information world are interconnected and use each other. This research not only opens the door for the transition from molecular sensing to molecular informatization but also provides an excellent opportunity for the construction of the "metaverse" of the molecular world.

Peptide-Based Sensing, Logic Computing, and Information Security on the Antimonene Platform.

Peptides have higher information density than DNA and equivalent molecular recognition ability and durability. However, there are currently no reports on the comprehensive use of peptides' recognition ability and structural diversity for sensing, logic computing, information coding, and protection. Herein, we, for the first time, demonstrate peptide-based sensing, logic computing, and information security on the antimonene platform. The molecular recognition capability and structural diversity (amino acid sequence) of peptides (Pb2+-binding peptide DHHTQQHD as a model) adsorbed on the antimonene universal fluorescence quenching platform were comprehensively utilized to sense targets (Pb2+) and give a response (fluorescence turn-on) and then to encode, encrypt, and hide information. Fluorescently labeled peptides used as the recognition probe and the information carrier were quenched and hidden by the large-plane two-dimensional material antimonene and specifically bound by Pb2+ as the stego key, resulting in fluorescence recovery. The above interaction and signal change can be considered as a peptide-based sensing and steganographic process to further implement quantitative detection of Pb2+, complex logic operation, information coding, encrypting, and hiding using a peptide sequence and the binary conversion of its selectivity. This research provides a basic paradigm for the construction of a molecular sensing and informatization platform and will inspire the development of biopolymer-based molecular information technology (processing, communication, control, security).

DNA nanosensing systems for tunable detection of metal ions and molecular crypto-steganography.

Various sensing platforms based on molecular or nanosystems are widely exploited through molecular diversity and specific recognition. However, it is extremely challenging to develop systems with tunable sensing ability and utilize the systems as information carriers/covers for communication and safety. Herein, DNA nanosensing systems based on cobalt oxyhydroxide (CoOOH) nanosheets were constructed for tunable detection and valence distinction of metal ions, molecular crypto-steganography, and information coding. CoOOH nanosheets absorb fluorescence-labeled single-stranded DNA with different bases and lengths, resulting in fluorescence quenching. The binding priority of bases with CoOOH nanosheets was guanine (G) > cytosine (C) > adenine (A) ≈ thymine (T) and the short chain excelled long chain. Due to the differences in the interaction among CoOOH, DNA, metal ions and variability of DNA bases, various DNA-CoOOH nanosystems have significantly different selective response patterns (that is selectivity) to metal ions and tunable linear ranges to Fe3+, Hg2+, Cr3+. Interestingly, by utilizing their molecular diversity, recognition, selective patterns, DNA-CoOOH sensing systems can be served as doubly cryptographic and steganographic systems to implement information encoding, encryption, and hiding and to reversely improve the selectivity of metal ions. This study provides an idea and platform for adjustable detection and valence distinction of metal ions, and gives a set of "molecular programming languages" for designing intelligent programmable sensing and molecular information communication and safety systems.

Multifunctional Carbon Nanocomposites as Nanoneurons from Multimode and Multianalyte Sensing to Molecular Logic Computing, Steganography, and Cryptography.

Inspired by information exchange and logic functions of life based on molecular recognition and interaction networks, ongoing efforts are directed toward development of molecular or nanosystems for multiplexed chem/biosensing and advanced information processing. However, because of their preparation shortcomings, poor functionality, and limited paradigms, it is still a big challenge to develop advanced nanomaterials-based systems and comprehensively realize neuron-like functions from multimode sensing to molecular information processing and safety. Herein, using fish scales derived carbon nanoparticles (FSCN) as a reducing agent and stabilizer, a simple one-step synthesis method of multifunctional silver-carbon nanocomposites (AgNPs-FSCN) is developed. The prepared AgNPs-FSCN own wide antibacterial and multisignal response abilities in five channels (including color, Tyndall, absorption and fluorescence intensities, and absorption wavelength) for quantitative colorimetric and fluorescence sensing of H2 O2 , ascorbic acid, and dopamine. Benefiting from its multicoding stimuli-responsive ability, molecular concealment, and programmability, AgNPs-FSCN can be abstracted as nanoneurons for implementing batch and parallel molecular logic computing, steganography, and cryptography. This research will promote the preparation of advanced multifunctional nanocomposites and the development of their multipurpose applications, including the multireadout-guided multianalyte intelligent sensing and sophisticated molecular computing, communication, and security.

Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.

Glioblastoma (GBM) is one of the most lethal tumor of all human cancers. Due to its poor response to chemotherapy and radiotherapy as well as its high rate of recurrence after treatment, the treatment is still undesired. The identification of potential related genes and bio-markers in the development of GBM could provide some new targets for the treatment of GBM. Our purpose in this study was to evaluate the mission of COL8A2 in GBM. Combined with TCGA, Oncomine databases, CGGA, GEPIA website and qRT-PCR analyses, we found that COL8A2 was up-regulated both in GBM tissues and cells compared to the controls. Moreover, the high COL8A2 expression was associated with the shorter overall survival of patients with GBM. The expression of COL8A2 was also positively correlated with metastasis-associated genes including vimentin, snail, slug, MMP2 and MMP7 according to GEPIA website. Knockdown of COL8A2 could suppress the cell proliferation, cell migration and invasion, whereas the overexpression of COL8A2 significantly expedited these processes. What's more, the outcome of western blot analysis manifested that COL8A2 could induced the expression of vimentin, snail, slug, MMP2 and MMP7. Taken together, COL8A2 activated cell proliferation, cell migration and invasion via raising the relative expression of EMT-related proteins in GBM. Therefore, our investigation suggests the oncogenic role of COL8A2 in GBM and provides a potential application of COL8A2 for GBM therapy.

LncRNA MALAT1 inhibits apoptosis of endometrial stromal cells through miR-126-5p-CREB1 axis by activating PI3K-AKT pathway.

Endometriosis is a common, chronic and painful disease in women, whose pathogenesis remains not entirely clear. Long non-coding RNA (lncRNA) MALAT1 participates in the development of endometriosis. This study further investigated the regulation of MALAT1-miR-126-5p-CREB1 axis in the pathological process of endometriosis. MALAT1, miR-126-5p, and CREB1 levels in human endometrial stromal cells (HESCs) were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein levels were determined by Western blotting. Cell viability and apoptosis was assessed by MTT assay and annexin V-FITC staining, respectively. The interactivity between miR-126-5p and MALAT1 (or CREB1) was assessed by dual luciferase reporter system. Knockdown of MALAT1 or CREB1 restrained proliferation and induced apoptosis as confirmed by upregulating cleaved caspase-3 and Bax, and down-regulating Bcl-2 in HESCs, while inhibition of miR-126-5p presented the opposite results. Moreover, silencing of MALAT1 triggered apoptosis of HESCs via targeting miR-126-5p. In addition, miR-126-5p directly regulated CREB1 expression via binding to its 3' non-coding region. Finally, miR-126-5p inhibitor-mediated apoptosis inhibition was restrained by CREB1 silencing via inactivation of PI3K-AKT pathway in HESCs. Taken together, our study firstly demonstrates that MALAT1 regulates apoptosis of HESCs through miR-126-5p/CREB1 axis mediated PI3K/AKT pathway. Our findings explained the pathogenesis of endometriosis and offered promising therapeutic option for endometriosis.

Long Non-Coding RNA LINC01783 Promotes the Progression of Cervical Cancer by Sponging miR-199b-5p to Mediate GBP1 Expression.

BACKGROUND: Long non-coding RNA showed potential regulating effects in oncogenesis. Highly expressed LncRNA LINC01783 is observed in cervical cancer. However, the specific pathogenesis of cervical cancer is still unclear. METHODS: Differential lncRNAs in cervical cancer were identified based on TCGA dataset. Subsequently, qRT-PCR was utilized for testing the LINC01783 expression in cervical cancer cell lines and normal human cervical epithelial cell line HcerEpic. CCK-8, EdU, Wound healing assay, Transwell assay and flow cytometry were used for detecting proliferative and migratory potential, cell cycle and apoptosis of cervical cancer cells, respectively. To identify the potential target of LINC01783, bioinformatics assay and dual-luciferase reporter gene assay were performed. Moreover, to clarify their interactions and roles in regulating the progression of cervical cancer, Western blot assay and RIP assay were carried out. RESULTS: Our results revealed LINC01783 is overexpressed in cervical cancer cells. Overexpressed LINC01783 considerably accelerated the cell proliferation, migration and invasion of cervical cancer cells while restrained cell apoptosis of them. Moreover, LINC01783 positively regulated the GBP1 expression via competitively binding to miR-199b-5p. CONCLUSION: LINC01783 is involved in the progression of cervical cancer through competitively binding to miR-199b-5p to mediate GBP1 expression.

Effects of menstrual blood­derived stem cells on endometrial injury repair.

The present study aimed to investigate the effects of menstrual blood­derived stem cells (MenSCs) on endometrial injury repair. MenSCs were isolated from human menstrual blood and were cultured in vitro. Flow cytometric analysis of cells in the third generation demonstrated that MenSCs exhibited higher expression levels of cluster of differentiation (CD)90 and lower expression levels of CD146, which suggested that the MenSCs were cultured successfully. A mechanical damage model of unilateral (right) endometrium was established in BALB/c nude mice, which were divided into four groups, Normal, negative control (NC), Model and MenSC. MenSCs transfected with adenovirus­enhanced green fluorescent protein were transplanted into the right uterine cavity of mice in the MenSC and NC groups. The protein expression levels of keratin, vimentin, and vascular endothelial growth factor (VEGF) and the average endometrial thickness were measured by immunohistochemistry; the average optical density of vimentin, VEGF and keratin in the MenSC­treated group was significantly higher compared with the untreated Model group. Fertility tests were performed to determine the pregnancy rate of each group; following endometrial damage in BALB/c nude mice, endometrial thickness was decreased in the Model group, whereas model mice treated with MenSC exhibited increased endometrial thickness and increased the pregnancy rates. Therefore, MenSCs may promote the repair of endometrial lesions in mice by promoting the expression of vimentin, VEGF and keratin.

Stem cell repair of intrauterine adhesions: preliminary achievements and clinical translation / 中国组织工程研究

BACKGROUND: Stem cells exhibit immeasurable application potentials in tissue and organ repair, but stem cell transplantation for the treatment of intrauterine adhesions is still in the initial stage. OBJECTIVE: To review the research progress in the stem cell repair of intrauterine adhesions. METHODS: We retrieved ISI Web of Science database, PubMed database and CNKI database for representative clinical research, basic research and reviews concerning stem cell therapy for intrauterine adhesions. The keywords were "intrauterine adhesion, metrosynizesis, Asherman's syndrome, stem cell, endometrial stem cell, stem cell transplantation" in English and Chinese, respectively. After repetitive studies were excluded, 43 articles were reviewed in the result analysis. RESULTS AND CONCLUSION: Hysteroscopic transcervical resection of adhesions is an ideal treatment for intrauterine adhesions, but the postoperative recurrence rate of intrauterine adhesions is still high. The human endometrium has high proliferative activity, and the endometrium of a woman of childbearing age may experience growth, differentiation and exfoliation for over 400 times, indicating the existence of endometrial stem cells.Endometrial stem cells have been isolated from the endometrium,successfully cultured in vitro and induced for directional differentiation. However, studies on endometrial stem cell transplantation for intrauterine adhesions are still in its infancy. Basic research on stem cells will facilitate its application to clinical practice.

MicroRNA-29b Inhibits Angiogenesis by Targeting VEGFA through the MAPK/ERK and PI3K/Akt Signaling Pathways in Endometrial Carcinoma.

OBJECTIVE: The purpose of this study is to explore the effects of microRNA-29b (miR-29b) regulating MAPK/ERK and PI3K/Akt signaling pathways on angiogenesis in endometrial carcinoma (EC) by targeting VEGFA. METHODS: Between February 2013 and April 2015, 126 EC patients admitted to the Second Affiliated Hospital of Nanchang University were randomly selected, with 126 EC tissues and the corresponding adjacent normal tissues collected after surgery. The human EC cell lines RL-95-2 and HEC-1-B and human endometrial cells were assigned to the normal group (human endometrial cells), the blank group (untransfected RL-95-2 or HEC-1-B cells), the pMIR-control group (RL-95-2 or HEC-1-B cells transfected with an empty vector), the pMIR-miR-29b group (RL-95-2 or HEC-1-B cells transfected with the miR-29b plasmid), LNA-control group (RL-95-2 or HEC-1-B cells transfected with an oligonucleotide inhibitors control), the LNA-miR-29b inhibitors group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors), the LNA-miR-29b inhibitors + PD98059 group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and PD98059, an inhibitor of the MAPK/ERK signaling pathway) and the LNA-miR-29b inhibitors + wortmannin group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and wortmannin, an inhibitor of the PI3K/Akt signaling pathway). qRT-PCR and Western blotting were conducted to detect the miR-29b expression and the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2. Immunohistochemistry (IHC) was performed to determine the microvessel density (MVD) expression in the EC tissues, adjacent normal tissues and nude-mice. RESULTS: Compared with the adjacent normal tissues, miR-29b expression was down-regulated, the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were up-regulated, and MVD expression was increased in the EC tissues. Compared with the normal group, miR-29b expression was down-regulated, while the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were up-regulated in the other groups. Compared with the blank, pMIR-control and LNA-control groups, miR-29b expression was increased, while mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were decreased in the pMIR-miR-29b group. The LNA-miR-29b inhibitors group exhibited elevated miR-29b expression and decreased mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 (All P < 0.05). Additionally, miR-29b expression was reduced in the LNA-miR-29b inhibitors + PD98059 and LNA-miR-29b inhibitors + wortmannin groups. In comparison to the normal group, MVD expression was elevated in the other groups. Compared with the blank, pMIR-control, LNA-control, LNA-miR-29b inhibitors + PD98059 and LNA-miR-29b inhibitors + wortmannin groups, MVD expression was decreased in the pMIR-miR-29b group but increased in the LNA-miR-29b inhibitors group. CONCLUSION: Our results indicate that miR-29b negatively modulates the MAPK/ERK and PI3K/Akt signaling pathways to inhibit angiogenesis in EC by targeting VEGFA.

Efficient delivery of docetaxel for the treatment of brain tumors by cyclic RGD-tagged polymeric micelles.

The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood­brain­tumor barrier. In the present study, cyclic Arginine­Glycine­Aspartic acid­D­Tyrosine­Lysine [c(RGDyK)], that has a high binding affinity to integrin αvß3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid­polyethylene glycol (DTX­PLA­PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine­Glycine­Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX­PLA­PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non­targeted micelles showed limited transport ability. Furthermore, RGD­linked micelles showed marked anti­glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand­mediated drug delivery may improve the efficacy of brain cancer chemotherapy.

Triptolide avoids cisplatin resistance and induces apoptosis via the reactive oxygen species/nuclear factor-κB pathway in SKOV3PT platinum-resistant human ovarian cancer cells.

An acquired resistance to platinum-based drugs has emerged as a significant impediment to effective ovarian cancer therapy. The present study explored the anticancer mechanisms of triptolide (TPL) in SKOV3PT platinum-resistant human ovarian cancer cells and observed that TPL activated caspase 3 and induced the dose-dependent apoptosis of the SKOV3PT cells. Furthermore, TPL inhibited complex I of the mitochondrial respiratory chain (MRC) followed by an increase of reactive oxygen species (ROS), which further inhibited nuclear factor (NF)-κB activation and resulted in the downregulation of anti-apoptotic proteins, Bcl-2 and X-linked inhibitor of apoptosis protein (XIAP). Notably, the pre-treatment with N-acetyl-L-cysteine (NAC) abolished the TPL-induced ROS generation, NF-κB inhibition and cell apoptosis, but did not affect the inhibitory effect of TPL on complex I activity. These results suggested that TPL negatively regulated the NF-κB pathway through mitochondria-derived ROS accumulation, promoting the apoptosis of the SKOV3PT cells. Furthermore, TPL synergistically enhanced the cytotoxicity of cisplatin against platinum-resistant ovarian cancer cells. Collectively, these findings suggest that TPL is able to overcome chemoresistance and that it may be an effective treatment for platinum-resistant ovarian cancer, either alone or as an adjuvant therapy.

[Clinical application of Tripterygium wilfordi for treatment of gynecologic diseases].

Extract of Tripterygium wilfordi (TW) has obvious effects on anti-inflammation, anti-tumor, anti-fertility and immuno-regulation, and it is broadly applied in various clinical departments. Referred to the gynecologic diseases, clinical therapeutic trials of TW on endometriosis, leiomyoma uteri, dysfunctional uterine bleeding and some tumors of women have been carried out, and it can be proved an effective new drug for the treatment of gynecologic diseases.