Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo

2020 ◽  
Vol 21 (13) ◽  
pp. 996-1008
Author(s):  
Mengli Wang ◽  
Qiuzheng Du ◽  
Lihua Zuo ◽  
Peng Xue ◽  
Chao Lan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Research Progress ◽  
Future Research ◽  
Pharmacokinetic Parameters ◽  
Molecular Characteristics ◽  
Targeted Drugs

Background: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. Methods: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. Results: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. Conclusion: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

scholarly journals Research on the Operating Characteristics of Hydraulic Free-Piston Engines: A Systematic Review and Meta-Analysis

Energies ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3530
Author(s):  
Fukang Ma ◽  
Shuanlu Zhang ◽  
Zhenfeng Zhao ◽  
Yifang Wang
Keyword(s):  
Systematic Review ◽  
High Efficiency ◽  
Meta Analysis ◽  
Combustion Process ◽  
Research Progress ◽  
Future Research ◽  
Operating Characteristics ◽  
Piston Engine ◽  
Free Piston ◽  
Free Piston Engine

The hydraulic free-piston engine (HFPE) is a kind of hybrid-powered machine which combines the reciprocating piston-type internal combustion engine and the plunger pump as a whole. In recent years, the HFPE has been investigated by a number of research groups worldwide due to its potential advantages of high efficiency, energy savings, reduced emissions and multi-fuel operation. Therefore, our study aimed to assess the operating characteristics, core questions and research progress of HFPEs via a systematic review and meta-analysis. We included operational control, starting characteristics, misfire characteristics, in-cylinder working processes and operating stability. We conducted the literature search using electronic databases. The research on HFPEs has mainly concentrated on four kinds of free-piston engine, according to piston arrangement form: single piston, dual pistons, opposed pistons and four-cylinder complex configuration. HFPE research in China is mainly conducted in Zhejiang University, Tianjin University, Jilin University and the Beijing Institute of Technology. In addition, in China, research has mainly focused on the in-cylinder combustion process while a piston is free by considering in-cylinder combustion machinery and piston dynamics. Regarding future research, it is very important that we solve the instabilities brought about by chance fluctuations in the combustion process, which will involve the hydraulic system’s efficiency, the cyclical variation, the method of predicting instability and the recovery after instability.

scholarly journals Current Perspectives and Potential of Probiotics to Limit Foodborne Campylobacter in Poultry

2020 ◽  
Vol 11 ◽  
Author(s):  
Wenjun Deng ◽  
Dana K. Dittoe ◽  
Hilary O. Pavilidis ◽  
William E. Chaney ◽  
Yichao Yang ◽  
...  
Keyword(s):  
Foodborne Pathogen ◽  
Research Progress ◽  
Feed Additive ◽  
Future Research ◽  
Host Animal ◽  
Health And Nutrition ◽  
Efficient Control ◽  
Pathogen Colonization

Poultry has been one of the major contributors of Campylobacter related human foodborne illness. Numerous interventions have been applied to limit Campylobacter colonization in poultry at the farm level, but other strategies are under investigation to achieve more efficient control. Probiotics are viable microbial cultures that can establish in the gastrointestinal tract (GIT) of the host animal and elicit health and nutrition benefits. In addition, the early establishment of probiotics in the GIT can serve as a barrier to foodborne pathogen colonization. Thus, probiotics are a potential feed additive for reducing and eliminating the colonization of Campylobacter in the GIT of poultry. Screening probiotic candidates is laborious and time-consuming, requiring several tests and validations both in vitro and in vivo. The selected probiotic candidate should possess the desired physiological characteristics and anti-Campylobacter effects. Probiotics that limit Campylobacter colonization in the GIT rely on different mechanistic strategies such as competitive exclusion, antagonism, and immunomodulation. Although numerous research efforts have been made, the application of Campylobacter limiting probiotics used in poultry remains somewhat elusive. This review summarizes current research progress on identifying and developing probiotics against Campylobacter and presenting possible directions for future research efforts.

Oxocarbon Organic Conjugated Compounds for Lithium-ion Batteries and Solar Cells: Progress and Perspectives

2020 ◽  
Vol 24 (2) ◽  
pp. 200-215
Author(s):  
Lihong Liu ◽  
Boshi Cheng ◽  
Zhengwei Yang ◽  
Huifeng Wang ◽  
Chuang Yue ◽  
...  
Keyword(s):  
Solar Cells ◽  
Energy Storage ◽  
High Efficiency ◽  
Lithium Ion ◽  
Energy System ◽  
Green Energy ◽  
Research Progress ◽  
Energy Storage Materials ◽  
Future Research ◽  
Conjugated Compounds

In recent years, with the continuous depletion of traditional fossil energy, the research of new energy storage materials has become one of the important ways to solve the issue of energy depletion. Generally, in an energy storage system, lithium-ion battery (LIB) has been widely applied in electronic intelligent devices and electrical vehicles (EVs). In an energy conversion system, as the most promising green energy system, solar cells have become a hot research field for scientists. Most recently, oxocarbon organic conjugated compounds (OOCCs) have been widely used in LIBs and solar cells due to their advantages such as abundant raw materials, environmental friendliness and high efficiency. As in this paper, the research progress of LIBs and solar cells based on OOCCs is reviewed, the synthesis strategies of these organic energy storage/conversion materials are summarized and the future research direction of organic energy materials is also prospected.

Applications of ROS-Induced Zr-MOFs Platform in Multimodal Synergistic Therapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Qiongjie Ding ◽  
Yiwei Liu ◽  
Chuncheng Shi ◽  
Jifei Xiao ◽  
Wei Dai ◽  
...  
Keyword(s):  
Drug Delivery ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Antitumor Effects ◽  
Metal Organic ◽  
Low Toxicity ◽  
Therapeutic Mechanisms ◽  
Biological Performance

Background: Metal-organic frameworks (MOFs) exhibited the adjustable aperture, high load capacities, tailorable structures, and excellent biocompatibilities that have used to be as drug delivery carries in cancer therapy. Until now, Zr-MOFs in particular combine optimal stability towards hydrolysis and postsynthetic modification with low toxicity, and are widely studied for its excellent biological performance. Introduction: This review comprises the exploration of Zr-MOFs as drug delivery devices (DDSs) with focus on various new methods, including chemotherapy (CT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy(SDT), radiotherapy, immunotherapy, gene therapy and related combined therapies, which all generate reactive oxygen species (ROS) to achieve the high efficiency of tumor therapy. Conclusion: We described and summarized these pertinent examples of the therapeutic mechanisms and highlight the antitumor effects of their biological application both in vitro and in vivo. The perspectives on their future applications and analogous challenge of the Zr-MOFs materials are given.

scholarly journals Potential Activity Mechanisms of Aesculus hippocastanum Bark: Antioxidant Effects in Chemical and Biological In Vitro Models

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 995
Author(s):  
Aleksandra Owczarek ◽  
Joanna Kolodziejczyk-Czepas ◽  
Joanna Woźniak-Serwata ◽  
Anna Magiera ◽  
Natalia Kobiela ◽  
...  
Keyword(s):  
High Efficiency ◽  
Herbal Remedy ◽  
Preliminary Investigation ◽  
Coagulation Cascade ◽  
Aesculus Hippocastanum ◽  
Future Research ◽  
Protein Thiols ◽  
Vascular Insufficiency

The bark of Aesculus hippocastanum is an herbal remedy used in conditions connected with vascular insufficiency; however, there is a lack of data concerning its mechanisms of action. The present work is a preliminary investigation into some of the potential directions of the bark activity. The phytochemically (qualitative UHPLC-PDA-MS/MS and quantitative UHPLC-PDA assays) characterized extract and its four main constituents (esculin, fraxin, (‒)-epicatechin and procyanidin A2) were first evaluated in terms of their antioxidant capacity. All analytes demonstrated dose-dependent scavenging potential towards the most common in vivo oxidants, with particularly advantageous capacity of the extract and its flavan-3-ol constituents against peroxynitrite (3.37–13.26 mmol AA/g), hydroxyl radical (5.03–8.91 mmol AA/g) and superoxide radical (3.50–5.50 mmol AA/g). Moreover, even at low concentrations (1–5 µg/mL), they protected components of human plasma against oxidative damage inflicted by peroxynitrite, preventing oxidation of plasma protein thiols and diminishing the tyrosine nitration and lipid peroxidation. High efficiency of the analytes was also demonstrated in preventing the peroxynitrite-induced nitrative changes of fibrinogen (up to 80% inhibition for (−)-epicatechin at 50 µg/mL), an important protein of coagulation cascade. Additionally, the extract and its constituents had, at most, moderate inhibitory activity towards platelet aggregation induced by ADP and only negligible influence on clotting times. The results show that, among the investigated properties, the antioxidant activity might, to the highest extent, be responsible for the bark efficacy in vascular disorders, thus supporting its application in those conditions; they also indicate the directions for future research that would allow for better understanding of the bark activity.

Engineered Ɛ-decalactone lipomers by-pass the liver to selectively in vivo deliver mRNA to the lungs without targeting ligands

2021 ◽  
Author(s):  
Mahmoud Abd Elwakil ◽  
Tianle Gao ◽  
Takuya Isono ◽  
Yusuke Sato ◽  
Yaser H.A. Elewa ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
Real Potential ◽  
Small Molecule Drugs

RNA drugs hold real potential for tackling devastating diseases that are currently resistant to small molecule drugs or monoclonal antibodies. However, since these drugs are unstable in vivo and unable...

scholarly journals A Small Molecule Antagonist of PD-1/PD-L1 Interactions Acts as an Immune Checkpoint Inhibitor for NSCLC and Melanoma Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanyuan Wang ◽  
Tingxuan Gu ◽  
Xueli Tian ◽  
Wenwen Li ◽  
Ran Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Monoclonal Antibodies ◽  
Small Molecule ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Molecule Antagonist ◽  
Programmed Death

Immune checkpoint inhibitors, such as monoclonal antibodies targeting programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1), have achieved enormous success in the treatment of several cancers. However, monoclonal antibodies are expensive to produce, have poor tumor penetration, and may induce autoimmune side effects, all of which limit their application. Here, we demonstrate that PDI-1 (also name PD1/PD-L1 inhibitor 1), a small molecule antagonist of PD-1/PD-L1 interactions, shows potent anti-tumor activity in vitro and in vivo and acts by relieving PD-1/PD-L1-induced T cell exhaustion. We show that PDI-1 binds with high affinity to purified human and mouse PD-1 and PD-L1 proteins and is a competitive inhibitor of human PD-1/PD-L1 binding in vitro. Incubation of ex vivo activated human T cells with PDI-1 enhanced their cytotoxicity towards human lung cancer and melanoma cells, and concomitantly increased the production of granzyme B, perforin, and inflammatory cytokines. Luciferase reporter assays showed that PDI-1 directly increases TCR-mediated activation of NFAT in a PD-1/PD-L1-dependent manner. In two syngeneic mouse tumor models, the intraperitoneal administration of PDI-1 reduced the growth of tumors derived from human PD-L1-transfected mouse lung cancer and melanoma cells; increased and decreased the abundance of tumor-infiltrating CD8+ and FoxP3+ CD4+ T cells, respectively; decreased the abundance of PD-L1-expressing tumor cells, and increased the production of inflammatory cytokines. The anti-tumor effect of PDI-1 in vivo was comparable to that of the anti-PD-L1 antibody atezolizumab. These results suggest that the small molecule inhibitors of PD-1/PD-L1 may be effective as an alternative or complementary immune checkpoint inhibitor to monoclonal antibodies.

Monoclonal antibodies, small molecule inhibitors and antibody-drug conjugates as HER2 inhibitors

2020 ◽  
Vol 27 ◽  
Author(s):  
Xiu-Fang Li ◽  
Chen-Fu Liu ◽  
Guo-Wu Rao
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Growth Factor Receptor ◽  
Research Progress ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Her 2 ◽  
Epidermal Growth ◽  
Antibody Drug

: Overexpression of human epidermal growth factor receptor (HER)-2 is found in a variety of cancers, often portending poor clinical outcomes. Therefore, HER2 is an attractive target for treatment. This review describes the research progress of HER2 targeted inhibitors in recent years. Excellent reviews are available, so we focus on the development, mechanisms of action, and structure-activity relationships of different types of inhibitors, including monoclonal antibodies, small molecule inhibitors, and antibody-drug conjugates (ADCs). In addition, the differences among them are compared.

scholarly journals Extraction, Purification, Structural Characteristics, Biological Activities and Pharmacological Applications of Acemannan, a Polysaccharide from Aloe vera: A Review

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1554 ◽  
Author(s):  
Chang Liu ◽  
Yan Cui ◽  
Fuwei Pi ◽  
Yuliang Cheng ◽  
Yahui Guo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Biological Activities ◽  
Structural Characteristics ◽  
Research Work ◽  
Aloe Vera ◽  
Research Progress ◽  
Future Research ◽  
Clinical Experiments

: Aloe vera is a medicinal plant species of the genus Aloe with a long history of usage around the world. Acemannan, considered one of the main bioactive polysaccharides of Aloe vera, possesses immunoregulation, anti-cancer, anti-oxidation, wound healing and bone proliferation promotion, neuroprotection, and intestinal health promotion activities, among others. In this review, recent advancements in the extraction, purification, structural characteristics and biological activities of acemannan from Aloe vera were summarized. Among these advancements, the structural characteristics of purified polysaccharides were reviewed in detail. Meanwhile, the biological activities of acemannan from Aloe vera determined by in vivo, in vitro and clinical experiments are summarized, and possible mechanisms of these bioactivities were discussed. Moreover, the latest research progress on the use of acemannan in dentistry and wound healing was also summarized in details. The structure-activity relationships of acemannan and its medical applications were discussed. Finally, new perspectives for future research work on acemannan were proposed. In conclusion, this review summarizes the extraction, purification, structural characteristics, biological activities and pharmacological applications of acemannan, and provides information for the industrial production and possible applications in dentistry and wound healing in the future.

Research Progress on Pulverized Coal Concentration Detection Device

2021 ◽  
Vol 15 ◽  
Author(s):  
Yun-Tao Wu ◽  
Tian-Hu Wang ◽  
Jin Hua ◽  
He-Yuan Sun
Keyword(s):  
High Efficiency ◽  
Coal Dust ◽  
Coal Industry ◽  
Pulverized Coal ◽  
Detection Methods ◽  
Research Progress ◽  
Future Research ◽  
Detection Scheme ◽  
Advantages And Disadvantages ◽  
Dust Detection

Background: Pulverized coal detection is an indispensable detection measure in the coal industry. The current detection devices can be divided into two types: invasive and non-invasive. The coal dust detection methods and devices based on acoustics, optics, and electricity have been extensively studied. In order to achieve a high-efficiency online detection scheme, improving the accuracy and stability of the detection means is the primary goal of the research. Objective: The general problems and characteristics of coal dust detection device design are summarized, as well as recent technological developments and the needs for online testing to predict future research trends. Methods: The current typical detection devices are classified according to the detection principle and whether they invade the target, analyzing its advantages and disadvantages according to the device performance and application scenarios. Results: It has a beneficial effect on the design of the pulverized coal concentration detection device. Conclusion: The paper summarizes and analyzes several representative coal concentration detection device patents in recent years. Then it points out advantages and main problems. On this basis, the main development direction of the coal dust concentration detection device in the future is discussed.

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