PTX-RPPR, a conjugate of paclitaxel and NRP-1 peptide inhibitor to prevent tumor growth and metastasis.

Paclitaxel, a potent anti-tumor drug widely recognized for its therapeutic efficacy, has faced limitations in clinical application due to its poor solubility. The use of Cremophor EL (CrEL) as a cosolvent in paclitaxel injections has been associated with hypersensitivity reactions in some patients. To overcome these challenges, we have developed a novel conjugate by linking a neuropilin-1 targeting peptide, RPPR, to paclitaxel, resulting in PTX-RPPR.

Serum metabolomics study reveals a distinct metabolic diagnostic model for renal calculi.

Renal calculi (RC) represent a prevalent disease of the urinary system characterized by a high incidence rate. The traditional clinical diagnosis of RC emphasizes imaging and stone composition analysis. However, the significance of metabolic status in RC diagnosis and prevention remains unclear.

Transcriptome and proteome analyses reveal the mechanisms involved in polystyrene nanoplastics disrupt spermatogenesis in mice.

Nanoplastics have been demonstrated to be reproductively toxic to mammals. However, the mechanisms of nanoplastics induce reproductive damage in mammals, especially their effects on spermatogenesis, remain elusive. Herein, we explored the effects and underlying mechanisms of polystyrene nanoplastics (PS-NPs) on the testicular development of male mice after 28 days of exposure, representing the first systematic study of PS-NPs-induced male reproductive injury by integrating histomorphology, transcriptomics and proteomics.

Genetically predicted the causal relationship between gut microbiota and infertility: bidirectional Mendelian randomization analysis in the framework of predictive, preventive, and personalized medicine.

Objective: Several studies have reported the association between gut microbiota and infertility; however, the causal association between them remains unclear. This study aimed to explore the causal relationship between gut microbiota and infertility and evaluate how specific gut microbiota can support early monitoring and prevention of infertility in the context of predictive, preventive, and personalized medicine (PPPM/3PM).

Methods: The gut microbiota GWAS data included 18,340 individuals.

Construction of a peacock immortalized fibroblast cell line for avian virus production.

The mammalian-derived MDCK cells are the most widely used for avian virus vaccine production at present. The use of heterologous cell systems for avian virus preparation may cause security risks. An avian cell line is available for avian virus vaccines urgently needed.

Goose IRF7 is involved in antivirus innate immunity by mediating IFN activation.

Interferon regulatory factor (IRF) 3 and IRF7 are the most important nuclear transcription factors regulating type-I interferon (IFN) production in mammals and the IRF3 is missing in birds. Our previous study found that IFR7 is the most important IRF in chickens, however, its functions in geese remain unknown. We cloned goose IRF7 (GoIRF7) and conducted bioinformatics analyses to compare the chromosomal location and protein homology of IRF7 in different species.

Exploring the action of RGDV-gemcitabine on tumor metastasis, tumor growth and possible action pathway.

The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis. To confirm this hypothesis the activities of RGDV-gemcitabine inhibiting tumor metastasis in vitro and in vivo were presented for the first time. AFM (atomic force microscopy) imaged that RGDV-gemcitabine was able to adhere onto the surface of serum-starved A549 cells, to block the extending of the pseudopodia.

Discovery of novel (6S/12aS)-heptachpyridone capable of inhibiting thrombosis in vivo.

The in vitro conversion of (1S,3S)-1-dimethoxylethyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid, (1S,3S)-DCCA, in rat plasma is monitored by HPLC-FT-ICR-MS. We show that the in vitro conversion of (1S,3S)-DCCA in rat plasma for 1 h leads to forming (6S/12aS)-bisdimethoxyethylheptachpyridone, reflecting intermolecular condensation of (1S,3S)-DCCA, and the in vitro conversion of (6S/12aS)-bisdimethoxyethylheptachpyridone in rat plasma for 1 h leads to forming (6S/12aS)-heptachpyridone, reflecting hydrolysis of (6S/12aS)-bisdimethoxyethylheptachpyridone. At a dose of 1.

Development of 13-Cys-BBR as an Agent Having Dual Action of Anti-Thrombosis and Anti-Inflammation.

Background: There is a correlation between tumor and inflammation. The activity of 13-[CHCO-Cys(Bzl)-OBzl]-berberine (13-Cys-BBR) slowing tumor growth is higher than that of BBR. Whether the anti-inflammation activity of 13-Cys-BBR is higher than that of BBR remains unknown.

13-[CHCO-Cys-(Bzl)-OBzl]-Berberine: Exploring The Correlation Of Anti-Tumor Efficacy With ROS And Apoptosis Protein.

Background: The discovery of novel derivative of berberine (BBR) having higher anti-tumor activity in vivo is of clinical importance. In this profile, 13-[CHCO-Cys-(Bzl)-OBzl]-berberine (13-Cys-BBR) was prepared for related assays.

Purpose: The object of preparation and evaluation is to show the advantages of 13-Cys-BBR over BBR in both in vitro and in vivo anti-tumor actions, furthermore to correlate the proliferation of cancer cells with ROS formation and anti-apoptosis protein (XIAP) expression inside cancer cells.

RGDV-modified gemcitabine: a nano-medicine capable of prolonging half-life, overcoming resistance and eliminating bone marrow toxicity of gemcitabine.

Background: Gemcitabine has been widely used as a chemotherapeutic drug. However, drug resistance, short half-life and side effects seriously decrease its chemotherapeutic efficacy.

Purpose: The object of preparing RGDV-gemcitabine was to prolong the half-life, to overcome drug resistance and to eliminate bone marrow toxicity of gemcitabine.

Nano-scaled MTCA-KKV: for targeting thrombus, releasing pharmacophores, inhibiting thrombosis and dissolving blood clots in vivo.

Background: In vitro (1R,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxyl-Lys(Pro-Ala-Lys)-Arg-Gly-Asp-Val (MTCA-KKV) adheres activated platelets, targets P-selectin and GPIIb/IIIa. This led to the development of MTCA-KKV as thrombus targeting nano-medicine.

Methods: MTCA-KKV was characterized by nano-feature, anti-thrombotic activity, thrombolytic activity, thrombus target and targeting release.

Identification of urine biomarkers for calcium-oxalate urolithiasis in adults based on UPLC-Q-TOF/MS.

Urolithiasis is a common urological disease with a high morbidity and recurrence rate, of which calcium oxalate (CaOx) is the most common type of stone that underlies the disease. However, the potential metabolic mechanisms of CaOx urolithiasis remain unclear. The present study aimed to seek potential biomarkers and metabolic mechanisms of CaOx urolithiasis in adults.

Heptapeptide-based modification leading to enhancing the action of MTCA on activated platelets, P-selectin, GPIIb/IIIa.

Aim: The modification of platelet inhibitor to enhance its targeting capacity toward platelets is of clinical importance. Thus, (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (MTCA), a platelet inhibitor, was modified with Lys(Pro-Ala-Lys)-Arg-Gly-Asp-Val (KKV), platelet targeting peptide, to form MTCA-KKV.

Materials & Methods: MTCA and MTCA-KKV were synthesized to identify the effect of KKV modification on MTCA and platelets.

Design and synthesis of nanoscaled IQCA-TAVV as a delivery system capable of antiplatelet activation, targeting arterial thrombus and releasing IQCA.

Background: Arterial thrombosis has been associated with a series of pathological conditions, and the discovery of arterial thrombosis inhibitor is of clinical importance.

Methods: By analyzing the pharmacophores of anti-platelet agents, thrombus targeting peptide and anti-thrombotic nano-systems 3S-1,2,3,4-tetrahydroisoquino-line-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) was designed and prepared as a nano-scaled arterial thrombosis inhibitor.

Results: In vitro the nanoparticles of IQCA-TAVV were able to adhere onto the surface of activated platelets, attenuate activated platelets to extend pseudopodia and inhibit activated platelets to form aggregators.

Docking of THPDTPI: to explore P-selectin as a common target of anti-tumor, anti-thrombotic and anti-inflammatory agent.

The impact of soluble P-selectin on tumor growth, thrombosis and inflammation has been individually documented. Whether the down-regulation of P-selectin expression can simultaneously slow the tumor growth, inhibit the thrombosis and attenuate the inflammatory response remains unknown. In this context, (2'S,5'S)- tetrahydropyrazino[1',2':1,6]-di{2,3,4,9-tetrahydro-1-pyrido[3,4-b]indole}-1',4'-dione (THPDTPI) was designed as an inhibitor of P-selectin.

IQCA-TAVV: To explore the effect of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 on deep venous thrombosis.

Deep vein thrombosis (DVT) associates with considerable morbidity, functional disability and mortality. Due to the lack of suitable inhibitor the correlation of various factors in DVT onset remains unknown. In this context we analyzed the structure of anti-platelet aggregation agent, P-selectin down-regulator, GPIIb/IIIa down-regulator and anti-inflammatory agent, thereby designed N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)- Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) as an inhibitor of DVT to receive evaluations.

Docking based design of diastereoisomeric MTCA as GPIIb/IIIa receptor inhibitor.

In GPIIb/IIIa mediated arterial thrombosis platelet activation plays a central role. To discover platelet activation inhibitor the pharmacophores of GPIIb/IIIa receptor inhibitors and anti-thrombotic agents were analyzed. This led to the design of (1R,3S)- and (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acids as GPIIb/IIIa inhibitors.

-(3-hydroxymethyl-β-carboline-1-yl-ethyl- 2-yl)-l-Phe: development toward a nanoscaled antitumor drug capable of treating complicated thrombosis and inflammation.

It is well documented that the surfaces of cancer cells, activated platelets and inflammatory cells are rich in P-selectin. -(3-hydroxymethyl-β-carboline-1-yl-ethyl-2-yl)-l-Phe (HMCEF) is a P-selectin inhibitor capable of simultaneously inhibiting thrombosis and inflammation. Based on the knowledge that P-selectin is a common target for antithrombotic, anti-inflammatory and antitumor drugs, the aim of this study article was to estimate the possibility of HMCEF as a nanoscaled antitumor drug.

IQCA-TASS: a nano-scaled P-selectin inhibitor capable of targeting thrombus and releasing IQCA/TARGD(S)S in vivo.

Thrombosis is a serious threat to human health worldwide. Tetrahydroisoquinoline-3-carboxylic acid (IQCA) is an antithrombotic agent, while Thr-Ala-Arg-Gly-Asp(Ser)-Ser (TASS) can target thrombus. Herein, tetrahydro-isoquinoline-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Ser)-Ser (IQCA-TASS) was designed with the aim towards the discovery of a nano-delivery system for targeting thrombus.

Cholyl-l-lysine-carboxylbutyryl adriamycin prodrugs targeting chemically induced liver injury.

By use of carboxylbutyryl as a linker, adriamycin (ADR) and cholyl-l-Lys (an anti-inflammatory agent) were covalently conjugated and N-cholyl-N-(N-carbonylpropionoadriamycin)-l-Lys (BCBALys) was constructed as a liver-targeting nano-delivery system to release cholyl-l-Lys and protect the liver from CCl-induced injury. In ultrapure water and rat plasma, 10 M BCBALys formed nanoparticles of 42-231 nm in diameter and ∼116 nm in height. In a CCl-injured mouse model, however, only 2 µmol kg of BCBALys effectively protected the liver of the mice from injury, and the mouse liver histology showed no hepatic architecture loss and inflammatory cell infiltration.

DHDMIQK(KAP): a novel nano-delivery system of dihydroxyl-tetrahydro-isoquinoline-3-carboxylic acid and KPAK towards the thrombus.

Vascular thrombosis is a major risk of the onset of stroke and so novel therapeutic candidates have been attracting interest. In this context, here docking based computer assisted screening and mesoscale simulation were used to design N-[(S)-6,7-dihydroxy-1,1-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]-Lys(Pro-Ala-Lys), DHDMIQK(KAP), for inhibiting P-selectin expression. In vitro, 1 nM of DHDMIQK(KAP) effectively down-regulated P-selectin expression.

A novel lead of P-selectin inhibitor: Discovery, synthesis, bioassays and action mechanism.

By docking 126 derivatives of β-carboline-3-carboxylic acid, tetrahydro-β-carboline-3-carboxylic acid and indoloquinolizine into the active pocket of P-selectin (2-(3-(hydroxymethyl)-9H-pyrido[3,4-b]indol-1-yl)ethyl)-l-phenylalanine (HMCEF) was assigned a novel inhibitor. ELISA and flow cytometry experiments showed that HMCEF effectively down-regulated P-selectin expression and supported the rationality of the computer assistant screening, while UV spectrum experiments demonstrated that HMCEF directly bound to P-selectin. In vivo HMCEF dose dependently inhibited the rats and mice to form thrombus and had a minimal effective dose of 20nmol/kg, dose dependently inhibited inflammatory response of mice and had a minimal effective dose of 20nmol/kg.

RGD(F/S/V)-Dex: towards the development of novel, effective, and safe glucocorticoids.

Dexamethasone (Dex) is an effective glucocorticoid in treating inflammation and preventing rejection reaction. However, the side effects limit its clinical application. To improve its druggable profile, the conjugates of RGD-peptide-modified Dex were presented and their enhanced anti-inflammation activity, minimized osteoporotic action, and nanoscaled assembly were explored.

Tetrahydro-β-carboline-3-carboxyl-thymopentin: a nano-conjugate for releasing pharmacophores to treat tumor and complications.

To improve the therapeutic efficacy of cancer patients a novel conjugate of thymopentin (TP5) and (1S,3S)-1-methyl-tetrahydro-β-carboline-3-carboxylic acid (MTC) was presented. In water and mouse plasma MTCTP5 forms the nanoparticles of 14-139 nm in diameter, the suitable size for delivery in blood circulation. In mouse plasma MTCTP5 releases MTC, while in the presence of trypsin MTCTP5 releases MTC and TP5.