Treatment Of Human Diseases Research Articles

Role of Polymer Concentration on the Release Rates of Proteins from Single- and Double-Network Hydrogels

Controlled delivery of proteins has immense potential for the treatment of various human diseases, but effective strategies for their delivery are required before this potential can be fully realized. Recent research has identified hydrogels as a promising option for the controlled delivery of therapeutic proteins, owing to their ability to respond to diverse chemical and biological stimuli, as well as their customizable properties that allow for desired delivery rates. This study utilized alginate and chitosan as model polymers to investigate the effects of hydrogel properties on protein release rates. The results demonstrated that polymer properties, concentration, and crosslinking density, as well as their responses to pH, can be tailored to regulate protein release rates. The study also revealed that hydrogels may be combined to create double-network hydrogels to provide an additional metric to control protein release rates. Furthermore, the hydrogel scaffolds were also found to preserve the long-term function and structure of encapsulated proteins before their release from the hydrogels. In conclusion, this research demonstrates the significance of integrating porosity and response to stimuli as orthogonal control parameters when designing hydrogel-based scaffolds for therapeutic protein release.

Characterization and biodistribution of under-employed gene therapy vector AAV7.

The use of adeno-associated viruses (AAVs) as gene delivery vectors has vast potential for the treatment of many severe human diseases. Over one hundred naturally existing AAV capsid variants have been described and classified into phylogenetic clades based on their sequences. AAV8, AAV9, AAVrh.10, and other intensively studied capsids have been propelled into pre-clinical and clinical use, and more recently, marketed products; however, less-studied capsids may also have desirable properties (e.g., potency differences, tissue tropism, reduced immunogenicity, etc.) that have yet to be thoroughly described. These data will help build a broader structure-function knowledge base in the field, present capsid engineering opportunities, and enable the use of novel capsids with unique properties.

Epigenetic drugs: a new frontier in the treatment of heart failure

Uncovering the secrets of genome flexibility not only contributed to the development of research in this area, but also served as an impetus for the development of new treatments for human diseases. A better understanding of the biology of chromatin (DNA/histone complexes) and non-coding RNAs (ncRNAs) has enabled the development of epigenetic (epi) preparations capable of modulating transcriptional programs associated with cardiovascular disease. This is especially true in heart failure, where epigenetic mechanisms have been shown to underlie the development of several pathological processes such as left ventricular hypertrophy, fibrosis, cardiomyocyte apoptosis, and microvascular dysfunction. Targeting epigenetic signals may represent a promising approach, especially in patients with heart failure with preserved ejection fraction (HFpEF), where the prognosis remains poor and effective treatments are not yet available. Under these conditions, epigenetics can be used to develop individualized therapeutic approaches, paving the way for personalized medicine. Although the beneficial effects of epi-drugs are gaining more attention, the number of epigenetic compounds used in clinical practice remains low, suggesting the need to develop more selective epi-drugs. In this review, we present a list of new promising epi-drugs for the treatment of cardiovascular diseases, with a focus mainly on HFpEF. The therapeutic effect of these drugs is due to the impact on at least one of the three main epigenetic mechanisms: DNA methylation, histone modification, and non-coding RNA.

Unexpected rearrangement of ivermectin in the synthesis of new derivatives with trypanocidal and antiplasmodial activities

Ivermectin is a sixteen-membered macrolactone “wonder drug” of Nobel prize-honored distinction that exhibits a wide range of antiparasitic activities. It has been used for almost four decades in the treatment of various parasitic diseases in humans and animals. In this paper, we describe the synthesis of the first-in-class ivermectin derivatives obtained via derivatization of the C13 position, along with the unexpected rearrangement of the oxahydrindene (hexahydrobenzofuran) unit of the macrolide ring. The structural investigation of the rearrangement has been performed using the single-crystal X-ray diffraction method. The antiparasitic and cytotoxic activities of the newly synthesized derivatives were determined in vitro with the bloodstream form of Trypanosoma brucei brucei, the hepatic stage of Plasmodium berghei, and human leukemia HL-60 cells. The compounds with the highest trypanocidal activity were the C13-epi-2-chloroacetamide analogs of native (6h) or rearranged (7h) ivermectin. Both 6h and 7h displayed trypanocidal activities within a similar mid-nanomolar concentration range as the commercially used trypanocides suramin and ethidium bromide. Furthermore, 6h and 7h exhibited a comparable cytotoxic to trypanocidal ratio as the reference drug ethidium bromide. The double-modified compound 7a (C13-epi-acetamide of rearranged ivermectin) exhibited the highest activity against P. berghei grown in human hepatoma cells, which was 2.5 times higher than that of ivermectin. The findings of this study suggest that C13-epi-amide derivatives of ivermectin are suitable leads in the rational development of new antiparasitic agents.

Overlooked abiotic humification for kanamycin removal in kanamycin fermentation waste by tea polyphenols: New, environmentally friendly and specific

Kanamycin, a typical aminoglycoside antibiotic, is mainly used for the treatment of diseases in humans or animals, while the related antibiotic pollution has been regarded as a serious issue. In this study, a green novel approach to remove kanamycin was established, specifically, kanamycin was specifically removed through abiotic humification process with tea polyphenols (TPs) as the polyphenol donor. The results demonstrated that the kanamycin could be effectively removed by TPs under alkaline conditions, with a 99.9 % highest removal efficiency. Among the three factors (pH, temperature and MnO2 dosage) selected in this study, pH was the most critical factor, with an increase in reaction pH (>6.0) leading to a higher kanamycin removal efficiency, and the temperature and MnO2 dosage ranked as the second and third important factor. Furthermore, kanamycin was mainly removed by being transformed into humic-like acid (HLA) product, and the product antimicrobial activity could be significantly reduced (≥27). Finally, satisfying removal efficiency of kanamycin were observed during the application of TPs in kanamycin fermentation wastewater and kanamycin mycelial residue (KMR), with the highest kanamycin removal efficiency was 99.9 %, and 99.6 %, respectively. This study could also offer insights for the removal of other pollutants containing primary amine or polyphenols.

Ultrasound-assisted enzymatic extraction, structural characterization, and anticancer activity of polysaccharides from Rosa roxburghii Tratt fruit

In this work, Rosa roxburghii Tratt fruit polysaccharides (RPs) were extracted by ultrasound-assisted enzymatic method. The highest extraction yield of RPs was 4.78 ± 0.10 % under the optimal extraction conditions. Two purified fractions named RP1 and RP3 were obtained and systematically characterized by a combination strategy of FT-IR, monosaccharide composition, molecular weight distribution, methylation and 2D NMR spectroscopy analyses. Structural analysis showed that the main chain of RP1 was composed of rhamnogalacturonan type I (RG-I), while the side chains were rich in arabinogalactan and galactose. RP3 was composed of long homogalacturonan (HG) backbone interspersed with alternating sequences of RG-I domains, with galactose and arabinose side chains. RP1 and RP3 induced apoptosis of MCF-7 cells in a dose dependent manner in vitro especially for RP1, and had no effect on L929 cells. Furthermore, the possible anticancer mechanisms were revealed, and results suggested that RP1 induced apoptosis through ROS-dependent pathway and mitochondrial pathway. The results of this work not only provided an efficient extraction method and theoretical basis for the application of RPs, but also may contribute to develop novel functional foods or pharmaceutical products for the prevention and treatment of human breast cancer disease.

Study of Transcriptomic Analysis of Yak (Bos grunniens) and Cattle (Bos taurus) Pulmonary Artery Smooth Muscle Cells under Oxygen Concentration Gradients and Differences in Their Lung Histology and Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors.

The aim of this study was to investigate the molecular mechanisms by which hypoxia affects the biological behavior of yak PASMCs, the changes in the histological structure of yak and cattle lungs, and the relationships and regulatory roles that exist regarding the differences in the distribution and expression of PDK1 and its hypoxia-associated factors screened for their role in the adaptation of yak lungs to the plateau hypoxic environment. The results showed that, at the level of transcriptome sequencing, the molecular regulatory mechanisms of the HIF-1 signaling pathway, glucose metabolism pathway, and related factors (HK2/PGK1/ENO1/ENO3/ALDOC/ALDOA) may be closely related to the adaptation of yaks to the hypoxic environment of the plateau; at the tissue level, the presence of filled alveoli and semi-filled alveoli, thicker alveolar septa and basement membranes, a large number of erythrocytes, capillary distribution, and collagen fibers accounted for all levels of fine bronchioles in the lungs of yaks as compared to cattle. A higher percentage of goblet cells was found in the fine bronchioles of yaks, and PDK1, HIF-1α, and VEGF were predominantly distributed and expressed in the monolayers of ciliated columnar epithelium in the branches of the terminal fine bronchioles of yak and cattle lungs, with a small amount of it distributed in the alveolar septa; at the molecular level, the differences in PDK1 mRNA relative expression in the lungs of adult yaks and cattle were not significant (p > 0.05), the differences in HIF-1α and VEGF mRNA relative expression were significant (p < 0.05), and the expression of PDK1 and HIF-1α proteins in adult yaks was stronger than that in adult cattle. PDK1 and HIF-1α proteins were more strongly expressed in adult yaks than in adult cattle, and the difference was highly significant (p < 0.01); the relative expression of VEGF proteins was not significantly different between adult yaks and cattle (p > 0.05). The possible regulatory relationship between the above results and the adaptation of yak lungs to the plateau hypoxic environment paves the way for the regulatory mechanisms of PDK1, HIF-1α, and VEGF, and provides basic information for studying the mechanism of hypoxic adaptation of yaks in the plateau. At the same time, it provides a reference for human hypoxia adaptation and a target for the prevention and treatment of plateau diseases in humans and plateau animals.

Classification of Medical Plants Based on Hybridization of Machine Learning Algorithms

India is a nation where plants with significant medicinal value cover more than 37% of its land. Every plant is treated as having certain medicinal values, whether it be the roots, trunk, fruits, or leaves. Medical plants help in most of the treatments for human diseases if the plant species are identified more clearly. However, it is difficult for individuals to recognize the medical value of the plant accurately. In this work, we suggest a Hybrid model that overcomes this challenge by fusing together two types of classifiers to accurately identify medicinal plants. These classifiers include Support Vector Machines (SVMs) and Convolutional Neural Networks (CNNs). The proposed system has many advantages. The features are first extracted using a Convolutional Neural Network (CNN), and then the recognizer is a Support Vector Machine (SVM). It ensures that the proposed model automatically recognizes the features in the raw leaves and carries out classification using those features. The classifier has been applied to 72 different medical plant leaves and is above 97%. The results showcase that the proposed method is more advantageous than the single classifier for effectively recognizing medical plants.

The role of an amphiphilic helix and transmembrane region in the efficient acylation of the M2 protein from influenza virus

Protein palmitoylation, a cellular process occurring at the membrane-cytosol interface, is orchestrated by members of the DHHC enzyme family and plays a pivotal role in regulating various cellular functions. The M2 protein of the influenza virus, which is acylated at a membrane-near amphiphilic helix serves as a model for studying the intricate signals governing acylation and its interaction with the cognate enzyme, DHHC20. We investigate it here using both experimental and computational assays. We report that altering the biophysical properties of the amphiphilic helix, particularly by shortening or disrupting it, results in a substantial reduction in M2 palmitoylation, but does not entirely abolish the process. Intriguingly, DHHC20 exhibits an augmented affinity for some M2 mutants compared to the wildtype M2. Molecular dynamics simulations unveil interactions between amino acids of the helix and the catalytically significant DHHC and TTXE motifs of DHHC20. Our findings suggest that the binding of M2 to DHHC20, while not highly specific, is mediated by requisite contacts, possibly instigating the transfer of fatty acids. A comprehensive comprehension of protein palmitoylation mechanisms is imperative for the development of DHHC-specific inhibitors, holding promise for the treatment of diverse human diseases.

First person – Anu Prakash

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Anu Prakash is first author on ‘ Centrosome amplification promotes cell invasion via cell–cell contact disruption and Rap-1 activation’, published in JCS. Anu conducted the research described in this article while a PhD student in Dr Emer Bourke's lab at University of Galway, Ireland. She is currently looking for a job in the pharmaceutical industry. Her research interests are focused on clinical research and drug discovery to develop novel treatments for human diseases.

Bevacizumab Efficiently Inhibits VEGF-Associated Cellular Processes in Equine Umbilical Vein Endothelial Cells: An In Vitro Characterization.

Anti-VEGF agents were found to have clinical implications for the successful treatment of vascular-driven diseases in humans. In this study, a detailed biological characterization of bevacizumab in a variety of in vitro assays was carried out to determine the effect of bevacizumab on equine umbilical vein endothelial cells (EqUVEC). EqUVECs were harvested from umbilical cords of clinically healthy horses and exposed to different concentrations (1, 2, 4, 6, 8 mg/mL) of bevacizumab (Avastin®). Assays concerning the drug's safety (cell viability and proliferation assay) and efficacy (cell tube formation assay, cell migration assay, and Vascular endothelial growth factor (VEGF) expression) were carried out reflecting multiple cellular processes. Bevacizumab significantly decreased VEGF expression at all concentrations over a 72 h period. No cytotoxic effect of bevacizumab on EqUVECs was observed at concentrations of 4 mg/mL bevacizumab or lower. Incubated endothelial cells showed delayed tube formation and bevacizumab efficiently inhibited cell migration in a dose-dependent manner. Bevacizumab potently inhibits VEGF-induced cellular processes and could be a promising therapeutic approach in vascular-driven diseases in horses.

Identification of antioxidant compounds from the stem bark fraction of Strychnosinnocua Del.

Strychnos innocua is a shrub that is native to the tropic region of the world. It is used locally as food, medicine, fuel, and as an insect repellent. Extracts of this plant are used as an aphrodisiac and in the treatment of gonorrhoea, snakebite and dysentery. It has been proven to possess antioxidant and antimicrobial activities. There is little or no information on the identification and pharmacological activities of the chemical composition of the stem bark of this plant. The aim of this work is to identify the chemical compounds present in this plant and determine their antioxidant activities. The ethyl acetate extract of this plant was subjected to purification techniques which lead to the isolation of fraction SI1. The chemical composition of the fraction SI1 was then determined using gas chromatography–mass spectrometry (GCMS). Fractions SI1 was then analysed for its free radical scavenging potential using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and Ferric ion reducing antioxidant property (FRAP) assay. A total of thirty compounds were identified with the major compounds being Cyclohex-2-enone,3-)2H-tetrazol-5-yl amino) (15.83 %), N-hexadecanoic acid (38.21%), N-hexadecanoic acid (38.21%), Octadecanoic acid (13.41%), Cis-vaccenic acid (13.41 %). The DPPH radical scavenging potential of the fraction SI1 compares well with the standard, ascorbic acid with IC50 of 3.71 ± 0.31 μg/mL and 1.68 ± 1.27 μg/mL, respectively. At 500 μg/mL, the antioxidant potential of the standard ascorbic acid was 96.9% whereas the fraction SI1 had 62.1% free DPPH radical scavenging activity. The half-maximal inhibitory concentration (IC50) of SI1 observed is 0.0488 ± 0.01 nm, and 0.5375 ± 0.01 nm and for ascorbic acid. In conclusion, fraction SI1 can act as an antioxidant supplement for various applications in diverse fields of food, cosmetics, and medicine. Several compounds contained in the fraction SI1 may have contributed to the antioxidant properties of the fraction. The compounds identified could be useful precursors for the synthesis of therapeutic drugs associated with the treatment of human and animal diseases.

Structural Characterization and Cytotoxic Activity Evaluation of Ulvan Polysaccharides Extracted from the Green Algae Ulva papenfussii.

Ulvan, a sulfated heteropolysaccharide with structural and functional properties of interest for various uses, was extracted from the green seaweed Ulva papenfussii. U. papenfussii is an unexplored Ulva species found in the South China Sea along the central coast of Vietnam. Based on dry weight, the ulvan yield was ~15% (w/w) and the ulvan had a sulfate content of 13.4 wt%. The compositional constitution encompassed L-Rhamnose (Rhap), D-Xylose (Xylp), D-Glucuronic acid (GlcAp), L-Iduronic acid (IdoAp), D-Galactose (Galp), and D-Glucose (Glcp) with a molar ratio of 1:0.19:0.35:0.52:0.05:0.11, respectively. The structure of ulvan was determined using High-Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance spectroscopy (NMR) methods. The results showed that the extracted ulvan comprised a mixture of two different structural forms, namely ("A3s") with the repeating disaccharide [→4)-β-D-GlcAp-(1→4)-α-L-Rhap 3S-(1→]n, and ("B3s") with the repeating disaccharide [→4)-α-L-IdoAp-(1→4)-α-L-Rhap 3S(1→]n. The relative abundance of A3s, and B3s was 1:1.5, respectively. The potential anticarcinogenic attributes of ulvan were evaluated against a trilogy of human cancer cell lineages. Concomitantly, Quantitative Structure-Activity Relationship (QSAR) modeling was also conducted to predict potential adverse reactions stemming from pharmacological interactions. The ulvan showed significant antitumor growth activity against hepatocellular carcinoma (IC50 ≈ 90 µg/mL), human breast cancer cells (IC50 ≈ 85 µg/mL), and cervical cancer cells (IC50 ≈ 67 µg/mL). The QSAR models demonstrated acceptable predictive power, and seven toxicity indications confirmed the safety of ulvan, warranting its candidacy for further in vivo testing and applications as a biologically active pharmaceutical source for human disease treatment.

Multi-Omics Integration for the Design of Novel Therapies and the Identification of Novel Biomarkers.

Multi-omics is a cutting-edge approach that combines data from different biomolecular levels, such as DNA, RNA, proteins, metabolites, and epigenetic marks, to obtain a holistic view of how living systems work and interact. Multi-omics has been used for various purposes in biomedical research, such as identifying new diseases, discovering new drugs, personalizing treatments, and optimizing therapies. This review summarizes the latest progress and challenges of multi-omics for designing new treatments for human diseases, focusing on how to integrate and analyze multiple proteome data and examples of how to use multi-proteomics data to identify new drug targets. We also discussed the future directions and opportunities of multi-omics for developing innovative and effective therapies by deciphering proteome complexity.

Reading and erasing of histone crotonyllysine mimics by the AF9 YEATS domain and SIRT2 deacylase

Lysine acylations on histones and their recognition by chromatin-binding reader domains and removal by histone deacylases function as an important mechanism for eukaryotic gene regulation. Histone lysine crotonylation (Kcr) is an epigenetic mark associated with active transcription, and its installation and removal are dynamically regulated by cellular epigenetic enzymes. Here, we report binding studies and enzyme assays with histone H3K9 peptides bearing simplest Kcr analogs with varying hydrocarbon chain length, bulkiness, rigidity and polarity. We demonstrate that the AF9 YEATS domain displays selectivity for binding of different acylation modifications on histone H3K9 peptides and exhibits preference for bulkier cinnamoylated lysine over crotonylated lysine and its mimics. SIRT2 shows deacylase activity against most of acylated H3K9 peptides bearing different crotonyllysine mimics, however, it displays a poor ability for the removal of cinnamoyl and trifluorocrotonyl groups. These results demonstrate different substrate selectivities of epigenetic proteins acting on crotonyllysine and pave the way for rational design and development of AF9 YEATS and SIRT2 inhibitors for treatment of human diseases, including cancer.

Study of the Antimicrobial Activity and Synergistic Inhibitory Activity of Carica papaya leaves extract with Antibiotics on Escherichia coli

Street food is one of the major causes of diarrhoea and gastrointestinal infections. Escherichia coli are one of the major contributors for many gastrointestinal infections. Natural sources are used to derive drugs that play striking role in the prevention and treatment of human diseases. Ayurveda has described Earandakarkati (Carica papaya) in many digestive disorders. This study was carried out to show the antimicrobial activity of Erandakarkati (Carica papaya) leaves extract alone and in combination with the antibiotics including Penicillin, Erythromycin, Piperacillin and Norfloxacin using agar strip diffusion method to see whether they produce synergistic or an antagonistic effect against street food isolated Escherichia coli and diarrhoeal ETEC strain (as a control). Carica papaya leaves extract showed antibacterial effect. The only combination of papaya leaf extract with Piperacillin resulted into a synergistic effect while the other combinations exhibited an antagonistic effect.

Blazing a trail for the clinical use of rapamycin as a geroprotecTOR.

Treatment with rapamycin, an inhibitor of the mechanistic Target Of Rapamycin Complex One (mTORC1) protein kinase, has been repeatedly demonstrated to extend lifespan and prevent or delay age-related diseases in diverse model systems. Concerns over the risk of potentially serious side effects in humans, including immunosuppression and metabolic disruptions, have cautiously limited the translation of rapamycin and its analogs as a treatment for aging associated conditions. During the last decade, we and others have developed a working model that suggests that while inhibition of mTORC1 promotes healthy aging, many of the negative side effects of rapamycin are associated with "off-target" inhibition of a second mTOR complex, mTORC2. Differences in the kinetics and molecular mechanisms by which rapamycin inhibits mTORC1 and mTORC2 suggest that a therapeutic window for rapamycin could be exploited using intermittent dosing schedules or alternative rapalogs that may enable more selective inhibition of mTORC1. However, the optimal dosing schedules and the long-term efficacy of such interventions in humans are unknown. Here, we highlight ongoing or upcoming clinical trials that will address outstanding questions regarding the safety, pharmacokinetics, pharmacodynamics, and efficacy of rapamycin and rapalogs on several clinically oriented outcomes. Results from these early phase studies will help guide the design of phase 3 clinical trials to determine whether rapamycin can be used safely to inhibit mTORC1 for the treatment and prevention of age-related diseases in humans.

An Overview on Sources, Biosynthesis and Bioactivities of Osthole: A Potential Bioactive Compound

Abstract: Different plants are rich in medicinal properties, which nature has provided in abundance for the living beings of this earth. Since the dawn of time, nature has proven to be a rich source of bioactive scaffolds that have been exploited in the creation of pharmaceuticals. Osthole is a natural coumarin derivative and potential bioactive compound found in plants. Herein, we aimed to review the origins, biology and pharmacological profiles of osthole, a plant-derived coumarin that is found in a variety of therapeutic plants, including Cnidium monnieri. Osthole, also called 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one, is a naturally occurring coumarin found to be present in different plants of the Apiaceae family, i.e., Cnidium monnieri and Angelica pubescens. The biological potential of the osthole in medicine has been investigated using a variety of literature databases. This study gathered diverse scientific research data on osthole from various literature sources and analysed, including Scopus, Google Scholar, Web of Science and PubMed. From the collected data, it was found that osthole have potential pharmacological activities, such as anticancer, antioxidant, osteogenic, cardioprotective, antimicrobial, antiparasitic, anti-hyperglycaemic, neuroprotective, and antiplatelet. The data in this review paper supports the pharmacological potential of osthole, but to completely appreciate the pharmacological potential of this therapeutically powerful chemical, researchers must focus their efforts on further experimentation, biosafety profiling and synergistic effects of this compound. The purpose of this study was to learn more about the origins, biology, and therapeutic benefits of osthole in medicine in order to develop better treatments for human diseases.

Structure-based optimization of indoline-containing compounds as second generation inhibitors of NF-κB-inducing kinase (NIK)

Overactivation of NIK led to increased transcriptional activity of NF-κB2, which was associated with human metabolic diseases, immunological disorders, and cancer. Therefore, NIK inhibitors were pursued as a potential treatment of NIK-driven human diseases. The first generation of NIK inhibitors features propargylic alcohol moieties, which were metabolic soft spots that led to the discovery of a second generation of NIK inhibitors without a propargylic alcohol. In this study, a series of compounds were designed, synthesized, and evaluated as novel NIK inhibitors using a NIK kinase assay. To evaluate selectivity profiles of these inhibitors, the most potent compound 50 was tested over COT and other two panels of 31 kinases. In addition, 50 inhibited NIK-driven upregulation of CCL5 gene in primary hepatocytes and showed low cytotoxicity against normal kidney cells HEK-293. These attributes make 50 a promising candidate for future optimization aimed to increase potency and selectivity against NIK and NF-κB2 pathway.

Animal Models of Kidney Disease: Challenges and Perspectives.

Kidney disease is highly prevalent and affects about 850 million people worldwide. It is also associated with high morbidity and mortality, and current therapies are incurable and often ineffective. Animal models are indispensable for understanding the pathophysiology of various kidney diseases and for preclinically testing novel remedies. In the last two decades, rodents continue to be the most used models for imitating human kidney diseases, largely due to the increasing availability of many unique genetically modified mice. Despite many limitations and pitfalls, animal models play an essential and irreplaceable role in gaining novel insights into the mechanisms, pathologies and therapeutic targets of kidney disease. In this review, we highlight commonly used animal models of kidney diseases by focusing on experimental acute kidney injury, chronic kidney disease, and diabetic kidney disease. We briefly summarize the pathological characteristics, advantages and drawbacks of some widely used models. Emerging animal models such as mini-pig, salamander, zebrafish and drosophila, as well as human-derived kidney organoids and kidney-on-a-chip are also discussed. Undoubtedly, careful selection and utilization of appropriate animal models is of vital importance in deciphering the mechanisms underlying nephropathies and evaluating the efficacy of new treatment options. Such studies will provide a solid foundation for future diagnosis, prevention and treatment of human kidney diseases.