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Ren Fail 2022 Dec;44(1):923-932

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin.

Accumulating evidence has implicated that berberine (BBR) has a beneficial effect on diabetic kidney disease (DKD), but its mechanism is not clear. The aim of this study was to assess whether berberine could alleviate tubulointerstitial fibrosis and attenuate epithelial-to-mesenchymal transition (EMT) and its possible molecular mechanism. High-fat diet (HFD) followed by injection of STZ was used to induce diabetic rats . Read More

J Immunother Cancer 2022 May;10(5)

Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA

Background: Most pediatric cancers are considered immunologically cold with relatively few responding to immune checkpoint inhibition. We recently described an effective combination radio-immunotherapy treatment regimen ( ombination daptive- nnate immunotherapy egimen (CAIR)) targeting adaptive and innate immunity in 9464D-GD2, an immunologically cold model of neuroblastoma. Here, we characterize the mechanism of CAIR and the role of major histocompatibility complex class I (MHC-I) in the treatment response. Read More

J Immunother Cancer 2022 May;10(5)

Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China

Background: Immunotherapy for hepatocellular carcinoma (HCC) exhibits limited clinical efficacy due to immunosuppressive tumor microenvironment (TME). Tumor-infiltrating macrophages (TIMs) account for the major component in the TME, and the dominance of M2 phenotype over M1 phenotype in the TIMs plays the pivotal role in sustaining the immunosuppressive character. We thus investigate the effect of bufalin on promoting TIMs polarization toward M1 phenotype to improve HCC immunotherapy. Read More

Clin Immunol 2022 May 23:109045. Epub 2022 May 23.

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, PR China. Electronic address:

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Read More

Biochim Biophys Acta Gene Regul Mech 2022 May 23:194827. Epub 2022 May 23.

Guangdong Key Laboratory of Fermentation and Enzyme Engineering, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong Province 510006, PR China; Guangdong Provincial Key Laboratory of New and Renewable Energy Research and Development, Guangzhou 510640, PR China. Electronic address:

Human p53 is a transcription factor regulating the transcription of a variety of target genes. Under various stresses, its tumor suppressor function was activated by the phosphorylation of p53. In this study, we found that full-length wild-type p53 could form phase-separated condensates with the aggregation tendency in vitro and in vivo. Read More

Neurobiol Dis 2022 May 23:105775. Epub 2022 May 23.

Office of the Saskatchewan Multiple Sclerosis Clinical Research Chair, University of Saskatchewan, Saskatoon, SK S7K 0M7, Canada; Cameco MS Neuroscience Research Centre, College of Medicine, University of Saskatchewan, Saskatoon, SK S7K 0M7, Canada; Neurology Division, Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0X8, Canada; Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. Electronic address:

Neurodegeneration, the progressive loss or damage to neurons and axons, underlies permanent disability in multiple sclerosis (MS); yet its mechanisms are incompletely understood. Recent data indicates autoimmunity to several intraneuronal antigens, including the RNA binding protein (RBP) heterogenous nuclear ribonucleoprotein A1 (hnRNP A1), as contributors to neurodegeneration. We previously showed that addition of anti-hnRNP A1 antibodies, which target the same immunodominant domain of MS IgG, to mice with experimental autoimmune encephalomyelitis (EAE) worsened disease and resulted in an exacerbation of hnRNP A1 dysfunction including cytoplasmic mislocalization of hnRNP A1, stress granule (SG) formation and neurodegeneration in the chronic stages of disease. Read More

Biochim Biophys Acta Mol Basis Dis 2022 May 23:166452. Epub 2022 May 23.

Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi 710072, China; Department of Immunology, Fourth Military Medical University, 169 West Changle Road, Xi'an, Shaanxi 710032, China. Electronic address:

CD226 is a costimulatory molecule that regulates immune cell functions in T cells, natural killer cells, and macrophages. Because macrophage-derived foam cell formation is a crucial factor contributing to the development of atherosclerosis, we aimed to evaluate the potential roles of CD226 in the pathogenesis of atherosclerosis. The effects of CD226 on atherosclerosis were investigated in CD226 and apolipoprotein E double-knockout (CD226 ApoE) mice fed with a high-cholesterol atherogenic diet. Read More

Int J Pharm 2022 May 23:121851. Epub 2022 May 23.

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Electronic address:

Vulvar candidiasis (VVC) is a vaginitis caused by vaginal mucosa infection of Candida, which greatly impairs women's health. Although there are more and more thiazoles on the market, new classes of antifungal drugs are still missing, it is still challenging to treat azole-resistant candidal vaginitis. We found that L-Se-methylselenocysteine (L-SeMC) could effectively inhibit the growth of Candida albicans, reduce the density and length of the mycelia. Read More

Environ Pollut 2022 May 23:119519. Epub 2022 May 23.

Department of Environmental Health Science, Konkuk University, Seoul, 05029, Republic of Korea. Electronic address:

As a result of the efforts to introduce the principle of the 3Rs (replacement, reduction, and refinement) into animal testing, alternative in vitro skin corrosion test methods have been developed and standardized globally. However, alternative in vitro skin corrosion test methods have some limitations in terms of the use of humanely killed rats or commercial models and kits. The present study focused on the applicability of invertebrates as alternative in vivo skin models. Read More

Exp Eye Res 2022 May 23:109125. Epub 2022 May 23.

Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA. Electronic address:

The normal cornea has no blood vessels but has abundant innervation. There is emerging evidence that sensory nerves, originated from the trigeminal ganglion (TG) neurons, play a key role in corneal angiogenesis. In the current study, we examined the role of TG sensory neuron-derived calcitonin gene-related peptide (CGRP) in promoting corneal neovascularization (CNV). Read More

Microvasc Res 2022 May 23:104384. Epub 2022 May 23.

Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Institute of Life Sciences, Chongqing Medical University, Chongqing, PR China; Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address:

Aims: Inflammation is a key feature of endothelial dysfunction induced by angiotensin (Ang) II. The purpose of this study was to explore the role of Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in endothelial dysfunction in Ang II-induced hypertension.

Materials And Methods: We analyzed blood pressure and vascular function of wild-type (WT) and Nlrp3 knockout (Nlrp3) mice, treated with Ang II. Read More

J Biol Chem 2022 May 23:102063. Epub 2022 May 23.

Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address:

Tumor angiogenesis is closely associated with the metastasis and progression of non-small cell lung cancer (NSCLC), a highly vascularized solid tumor. However, novel therapeutics are lacking for the treatment of this cancer. Here, we developed a series of 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazol analogs (6a-6x) as colchicine binding site-tubulin inhibitors, aiming to find a novel promising drug candidate for NSCLC treatment. Read More

Exp Cell Res 2022 May 23:113213. Epub 2022 May 23.

Thoracic Surgery Laboratory, Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China; Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, China. Electronic address:

Purpose: The impairment of the coronary microcirculatory barrier caused by acute myocardial infarction (AMI) is closely related to poor prognosis. Recently, pigment epithelial-derived factor (PEDF) has been proven to be a promising cardiovascular protective drug. In this study, we demonstrated the protective role of PEDF in endothelial tight junctions (TJs) and the vascular barrier in AMI. Read More

Biochem Pharmacol 2022 May 23:115105. Epub 2022 May 23.

Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou 310018, Zhejiang, P.R. China; Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, P.R. China. Electronic address:

The application of lapatinib, a widely used dual inhibitor of human epidermal growth factor receptor 1 (EGFR/ERBB1) and 2 (HER2/ERBB2), has been seriously limited due to cutaneous toxicity. However, the specific mechanism of lapatinib-induced cutaneous toxicity has not been clarified, leading to the lack of an effective strategy to improve clinical safety. Here, we found that lapatinib could induce mitochondrial dysfunction, lead to DNA damage and ultimately cause apoptosis of keratinocytes. Read More

Immunity 2022 May 23. Epub 2022 May 23.

Committee on Immunology, University of Chicago, Chicago, IL 60637, USA; Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA. Electronic address:

Antigen cross-presentation, wherein dendritic cells (DCs) present exogenous antigen on major histocompatibility class I (MHC-I) molecules, is considered the primary mechanism by which DCs initiate tumor-specific CD8 T cell responses. Here, we demonstrate that MHC-I cross-dressing, an antigen presentation pathway in which DCs acquire and display intact tumor-derived peptide:MHC-I molecules, is also important in orchestrating anti-tumor immunity. Cancer cell MHC-I expression was required for optimal CD8 T cell activation in two subcutaneous tumor models. Read More

Biofabrication 2022 May 26. Epub 2022 May 26.

Department of Chemical Engineering Samuel Ginn College of Engineering, Auburn University, 212 Ross Hall, Auburn, AL 36849-5127 , USA, Auburn, Alabama, 36849-5412, UNITED STATES.

The development of physiologically relevant in vitro colorectal cancer (CRC) models is vital for advancing understanding of tumor biology. Although CRC patient-derived xenografts (PDX) recapitulate key patient tumor characteristics and demonstrate high concordance with clinical outcomes, the use of this in vivo model is costly and low-throughput. Here we report the establishment and in-depth characterization of an in vitro tissue-engineered CRC model using PDX cells. Read More

Biofabrication 2022 May 26. Epub 2022 May 26.

ETH Zurich Department of Health Sciences and Technology, Leopold-Ruzicka-Weg 4, Zurich, Zürich, 8093, SWITZERLAND.

Mechanical loading has been shown to influence various osteogenic responses of bone-derived cells and bone formation in vivo. However, the influence of mechanical stimulation on the formation of bone organoid in vitro is not clearly understood. Here, 3D bioprinted human mesenchymal stem cells (hMSCs)-laden graphene oxide composite scaffolds were cultured in a novel cyclic-loading bioreactors for up to 56 days. Read More

Biofabrication 2022 May 26. Epub 2022 May 26.

University Hospital Cologne, Robert Koch Str. 39, Koln, Nordrhein-Westfalen, 50931, GERMANY.

Multicellular agglomerates in form of irregularly shaped or spherical clusters can recapitulate cell-cell interactions and are referred to as microtissues. Microtissues gain increasing attention in several fields including cardiovascular research. Cardiac microtissues are evolving as excellent model systems for drug testing in vitro (organ-on-a-chip), are used as tissue bricks in 3D printing processes and pave the way for improved cell replacement therapies in vivo. Read More

Biofabrication 2022 May 26. Epub 2022 May 26.

Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA, Baltimore, Maryland, 21218-2625, UNITED STATES.

Porous Magnesium (Mg) is a promising biodegradable scaffold for treating critical-size bone defects, and as an essential element for human metabolism, Mg has shown sufficient biocompatibility. Its elastic moduli and yield strengths are closer to those of cortical bone than common, inert metallic implants, effectively reducing stress concentrations around host tissue as well as stress shielding. More importantly, Mg can degrade and be absorbed in the human body in a safe and controlled manner, thereby reducing the need for second surgeries to remove implants. Read More

Phytomedicine 2022 May 17;102:154178. Epub 2022 May 17.

Department of Cardiothoracic Surgery, Central Theater Command General Hospital of Chinese People's Liberation Army, 627 Wuluo Road, Wuhan 430070, China. Electronic address:

Background: Adriamycin (ADR), a high-efficiency, broad-spectrum anthraquinone chemotherapeutic agent, is currently used to treat various malignant tumors and can lead to cumulative, dose-dependent, and irreversible cardiotoxicity. Lycorine (LYC) is a benzyl phenethylamine alkaloid that exerts remarkable therapeutic effects on cancers and sepsis.

Purpose: However, researchers have not yet elucidated whether LYC exerts protective effects against cardiotoxicity induced by ADR and the possible molecular mechanisms. Read More

Eur J Med Chem 2022 May 17;238:114463. Epub 2022 May 17.

Department of Pharmacology, School of Pharmacy, Fuijan Provincial Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou, 350122, China. Electronic address:

Six positional isomers of triptolide-glucose conjugates (TG1α, TG1β, TG2, TG3, TG4 and TG6) were designed and synthesized. These conjugates exhibited better water solubility, and had selective cytotoxicity between tumor cells with high expression of glucose transport-1 (Glut-1) and non-tumor cells with low expression of Glut-1, in which TG2 formed by triptolide (TPL) and d-glucose C2-OH had the strongest cytotoxicity to tumor cells and lowest toxicity in non-tumor cells, therefore the highest relative therapeutic index, which was 5.7 times that of triptolide and consequent the most powerful selective antitumor activity in vitro. Read More

Eur J Med Chem 2022 May 11;238:114451. Epub 2022 May 11.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, PR China.

Herein, we report the discovery process and antitumor activity of the TRK inhibitor CZw-124 (8o), which is a quinazoline derivative. Starting from a PAK4 inhibitor, we used various drug design strategies, including pharmacophore feature supplementation, F-scanning, and blocking metabolic sites, and finally found a TRK inhibitor CZw-124 that is effective in vitro and in vivo. Docking studies and molecular dynamics simulations revealed a possible mode of binding of CZw-124 to TRKA. Read More

J Infect Public Health 2022 May 13;15(6):662-669. Epub 2022 May 13.

Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia. Electronic address:

Background: SARS-CoV-2, an emerged strain of corona virus family became almost serious health concern worldwide. Despite vaccines availability, reports suggest the occurrence of SARS-CoV-2 infection even in a vaccinated population. With frequent evolution and expected multiple COVID-19 waves, improved preventive, diagnostic, and treatment measures are required. Read More

Biomed Pharmacother 2022 May 23;151:113163. Epub 2022 May 23.

Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 1, 71013 San Giovanni Rotondo, FG, Italy. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. The characteristic excessive stromatogenesis accompanying the growth of this tumor is believed to contribute to chemoresistance which, together with drug toxicity, results in poor clinical outcome. An increasing number of studies are showing that gut microbiota and their metabolites are implicated in cancer pathogenesis, progression and response to therapies. Read More

Biomaterials 2022 May 20;286:121584. Epub 2022 May 20.

Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea; College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

In conventional chemotherapy, maximum tolerated dose approach is considered as a first-line medication for cancer treatment in clinics. In contrast to the conventional chemotherapy which has heavy tumor burdens arising from high dose treatment, metronomic chemotherapy (MCT) engages relatively low dose without drug-free breaks, and is recognized as a promising strategy for a long-term management of the disease. Although doxorubicin (DOX), an anthracycline anti-cancer drug, showed a potential of maintenance effect in vitro, further study on in vivo-relevant concentration to achieve tumor suppression with no toxicity is required to apply the MCT in clinicals. Read More

Biomaterials 2022 May 19;286:121577. Epub 2022 May 19.

School of Ophthalmology and Optometry, Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325000, PR China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, PR China; Oujiang Laboratory, Wenzhou, 325000, PR China.

Stubborn resistant bacteria, bacterial biofilms and severe inflammation are challenging issues in refractory keratitis treatment. Herein, we design a multifunctional near-infrared light-responsive nanoplatform for efficient therapy of refractory keratitis based on a "three-birds-with-one-stone" strategy, which integrates the bacteria targeting photodynamic therapy, nitric oxide (NO) sterilization, and NO-mediated anti-inflammatory property into one system. This nanoplatform (UCNANs) is constructed using the dual-emissive upconversion nanoparticles (UCNPs) as cores coated with mesoporous silica for the loading of photosensitizers with aggregation-induced emission (AIE) property and the grafting of NO donors and bacteria targeting molecules. Read More

PLoS One 2022 26;17(5):e0268645. Epub 2022 May 26.

Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa.

Previously, we had demonstrated that Escherichia coli O157:H7 (O157) strain 86-24 expresses proteins involved in survival rather than virulence in vitro in rumen fluid from dairy cattle limit fed a maintenance diet. Here, we verified if this observation would be true for different O157 strains grown in vitro in rumen fluid from, and in vivo in the rumen of, animals on contrasting maintenance (high fiber) and lactation (high energy-protein) diets usually limit fed to dairy cattle. For the in vivo studies, an economical, novel, reusable and non-terminal rumen-fistulated animal model permitting simultaneous evaluation of multiple bacterial strains in the bovine rumen was developed. Read More

PLoS One 2022 26;17(5):e0268924. Epub 2022 May 26.

Eastern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Wyndmoor, PA, United States of America.

Listeria monocytogenes is a foodborne pathogen and the causative agent of listeriosis, a disease associated with high fatality (20-30%) and hospitalization rates (>95%). ATP-Binding Cassette (ABC) transporters have been demonstrated to be involved in the general stress response. In previous studies, in-frame deletion mutants of the ABC transporter genes, LMOf2365_1875 and LMOf2365_1877, were constructed and analyzed; however, additional work is needed to investigate the virulence potential of these deletion mutants. Read More

PLoS Biol 2022 May 26;20(5):e3001624. Epub 2022 May 26.

Oncology Safety, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Boston, Massachusetts, United States of America.

Test compounds used on in vitro model systems are conventionally delivered to cell culture wells as fixed concentration bolus doses; however, this poorly replicates the pharmacokinetic (PK) concentration changes seen in vivo and reduces the predictive value of the data. Herein, proof-of-concept experiments were performed using a novel microfluidic device, the Microformulator, which allows in vivo like PK profiles to be applied to cells cultured in microtiter plates and facilitates the investigation of the impact of PK on biological responses. We demonstrate the utility of the device in its ability to reproduce in vivo PK profiles of different oncology compounds over multiweek experiments, both as monotherapy and drug combinations, comparing the effects on tumour cell efficacy in vitro with efficacy seen in in vivo xenograft models. Read More

Acta Biochim Pol 2022 May 26. Epub 2022 May 26.

Fundamentals of Integrated Traditional Chinese and Western Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Glaucoma is a common eye disease and a major cause of blindness. We designed brinzolamide (Brla)- and latanoprost (Ltp)-loaded nano-lipoidal carriers (NLCs) for glaucoma treatment. Brla and Ltp-loaded NLCs were designed and characterized by assessing the zeta potential, polydispersity index, X-ray diffraction and scanning electron microscopy images, and particle size. Read More