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Efficient conversion of human induced pluripotent stem cells into microglia by defined transcription factors.

Stem Cell Reports 2021 Mar 26. Epub 2021 Mar 26.

Brain Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan (ROC); Department of Life Sciences and Institute of Genome Sciences, School of Life Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan (ROC). Electronic address:

Microglia, the immune cells of the central nervous system, play critical roles in brain physiology and pathology. We report a novel approach that produces, within 10 days, the differentiation of human induced pluripotent stem cells (hiPSCs) into microglia (iMG) by forced expression of both SPI1 and CEBPA. High-level expression of the main microglial markers and the purity of the iMG cells were confirmed by RT-qPCR, immunostaining, and flow cytometry analyses. Read More

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Inhibition of Autophagy Does Not Affect Innate Cytokine Production in Human Lung Epithelial Cells During Respiratory Syncytial Virus Infection.

Viral Immunol 2021 Apr 9. Epub 2021 Apr 9.

Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Malaysia.

Human respiratory syncytial virus (RSV) is one of the major causes of childhood acute lower respiratory tract infection worldwide. Autophagy is an intracellular pathway involved in nutrient recycling. Recently, autophagy has been reported to play a role in regulating host cytokine response to several viruses, including vesicular stomatitis virus and human immunodeficiency virus. Read More

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Edaravone Alleviated Propofol-Induced Neurotoxicity in Developing Hippocampus by mBDNF/TrkB/PI3K Pathway.

Drug Des Devel Ther 2021 30;15:1409-1422. Epub 2021 Mar 30.

Department of Anesthesiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People's Republic of China.

Background: To investigate the neuroprotective effect of edaravone on excessive-dose propofol-induced neurotoxicity in the hippocampus of newborn rats and HT22 cells.

Methods: Cell proliferation was investigated by assessing ki67 expression in the neural stem of the hippocampus of newborn rats and by cell counting kit-8 (CCK8) assay in HT22 cells. Cell apoptosis was assessed in vivo by caspase 3 detection in Western blots and measurement of apoptosis in neurons and glial cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Read More

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Phase 1 trial of N-803, an IL-15 receptor agonist, with rituximab in patients with indolent non-Hodgkin lymphoma.

Clin Cancer Res 2021 Apr 8. Epub 2021 Apr 8.

Dept. of Medicine, Division of Oncology, Washington University in St. Louis School of Medicine

Purpose: N-803 is an IL-15 receptor superagonist complex, designed to optimize in vivo persistence and trans-presentation, thereby activating and expanding natural killer (NK) cells and CD8+ T cells. Monoclonal antibodies (mAb) direct FcR-bearing immune cells, including NK cells, to recognize and eliminate cancer targets. The ability of IL-15R agonists to enhance tumor-targeting mAbs in patients has not been previously reported. Read More

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Tumor suppressor role of hsa_circ_0035445 in gastric cancer.

J Clin Lab Anal 2021 Apr 8:e23727. Epub 2021 Apr 8.

The Affiliated People's Hospital, Ningbo University, Ningbo, China.

Circular RNAs (circRNAs) are closely related to the occurrence and development of cancers. However, the roles of circRNAs in gastric cancer are largely unknown. Total 104 pairs of gastric cancer tissues and non-cancer tissues, fasting plasma of 42 healthy people and 42 gastric cancer patients' one day before operation and 10 days after operation were collected. Read More

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A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans.

Front Immunol 2021 22;12:647873. Epub 2021 Mar 22.

Gothenburg University Vaccine Research Institute (GUVAX), Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Read More

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Macrophage migration inhibitory factor (MIF) enhances hypochlorous acid production in phagocytic neutrophils.

Redox Biol 2021 Mar 30;41:101946. Epub 2021 Mar 30.

Centre for Free Radical Research, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand. Electronic address:

Background: Macrophage migration inhibitory factor (MIF) is an important immuno-regulatory cytokine and is elevated in inflammatory conditions. Neutrophils are the first immune cells to migrate to sites of infection and inflammation, where they generate, among other mediators, the potent oxidant hypochlorous acid (HOCl). Here, we investigated the impact of MIF on HOCl production in neutrophils in response to phagocytic stimuli. Read More

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A rare germline CDKN2A variant (47T>G; p16-L16R) predisposes carriers to pancreatic cancer by reducing cell cycle inhibition.

J Biol Chem 2021 Apr 3:100634. Epub 2021 Apr 3.

Schulze Center for Novel Therapeutics, Division of Oncology Research. Electronic address:

Germline mutations in CDKN2A, encoding the tumor suppressor p16, are responsible for a large proportion of familial melanoma cases, and also increase risk of pancreatic cancer. We identified four families through pancreatic cancer probands that were affected by both cancers. These families bore a germline missense variant of CDKN2A (47T>G), encoding a p16-L16R mutant protein associated with high cancer occurrence. Read More

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Long non-coding RNA TDRG1 facilitates cell proliferation, migration and invasion in breast cancer via targeting miR-214-5p/CLIC4 axis.

Cancer Biol Ther 2021 Apr 6:1-9. Epub 2021 Apr 6.

Department of General Surgery, Qilu Hospital of Shandong University (Qingdao Branch), Qingdao, 266000, Shandong, China.

Accumulated studies have revealed the critical role of long non-coding RNAs (lncRNAs) in the carcinogenesis and progression of various cancers. LncRNA TDRG1 has been reported to exhibit oncogenic potential in some cancers. However, its underlying mechanism regulating breast cancer (BC) remains obscure. Read More

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Medical ozone induces proliferation and migration inhibition through ROS accumulation and PI3K/AKT/NF-κB suppression in human liver cancer cells in vitro.

Clin Transl Oncol 2021 Apr 5. Epub 2021 Apr 5.

Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China.

Background: Hepatocellular carcinoma is one of the most common malignancies and leading cancer-associated deaths worldwide. Ozone has been proposed as a promising therapeutic agent in the treatment of various disorders.

Purpose: The purpose of this paper is to assess the potential anticancer effects of the ozone on liver cancer cells. Read More

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Quantitative Approach for Protein Analysis in Small Cell Ensembles by an Integrated Microfluidic Chip with MALDI Mass Spectrometry.

Anal Chem 2021 Apr 5. Epub 2021 Apr 5.

School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287-1604, United States.

Increasing evidence has demonstrated that cells are individually heterogeneous. Advancing the technologies for single-cell analysis will improve our ability to characterize cells, study cell biology, design and screen drugs, and aid cancer diagnosis and treatment. Most current single-cell protein analysis approaches are based on fluorescent antibody-binding technology. Read More

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Integrin β3 overexpression contributes to podocyte injury through inhibiting RhoA/YAP signaling pathway.

Bioengineered 2021 Dec;12(1):1138-1149

Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Axis formed by integrin β3 (ITGβ3)-Ras homolog gene family, member A (RhoA), and Yes-associated protein (YAP) plays an important role in atherosclerosis. In addition, ITGβ3 overexpression was noted in high-glucose (HG) exposure podocytes. However, the ITGβ3-RhoA-YAP axis on HG-induced podocyte injury remains unclear. Read More

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December 2021

miR-299-3p suppresses cell progression and induces apoptosis by downregulating PAX3 in gastric cancer.

Open Life Sci 2021 23;16(1):266-276. Epub 2021 Mar 23.

Department of Gastrointestinal Surgery, Hainan General Hospital, No. 19 Xiuhua Rd, Xiuying District, 570311, Haikou, Hainan, China.

Gastric cancer (GC) is ranked the fourth leading cause of cancer-related death, with an over 75% mortality rate worldwide. In recent years, miR-299-3p has been identified as a biomarker in multiple cancers, such as acute promyelocytic leukemia, thyroid cancer, and lung cancer. However, the regulatory mechanism of miR-299-3p in GC cell progression is still largely unclear. Read More

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The lncRNA DLGAP1-AS1/miR-149-5p/TGFB2 axis contributes to colorectal cancer progression and 5-FU resistance by regulating smad2 pathway.

Mol Ther Oncolytics 2021 Mar 16;20:607-624. Epub 2021 Jan 16.

Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China.

Colorectal carcinoma (CRC) ranks as the third most common malignancy. Long non-coding RNA DLGAP1-AS1 was reported to be dysregulated and to play a pivotal role in hepatocellular carcinoma (HCC). This work aims to analyze the functions and molecular basis of DLGAP1-AS1 in CRC progression and 5-fluorouracil resistance. Read More

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Biochanin A Attenuates Ovariectomy-Induced Cognition Deficit Antioxidant Effects in Female Rats.

Front Pharmacol 2021 16;12:603316. Epub 2021 Mar 16.

Departments of Neuroscience and Behavioral Medicine and Psychiatry, Rockefeller Neurosciences Institute, West Virginia University Health Sciences Center, Morgantown, WV, United States.

Impairment of memory and cognition is one of the major symptoms in women with postmenopausal disorders due to estrogen deficiency, which accounts for the much higher prevalence of Alzheimer's disease in females. Biochanin A (BCA), a natural phytoestrogen, has been reported to protect neurons against ischemic brain injury. However, the neuroprotective effects of BCA in the postmenopausal-like model of ovariectomized (OVX) rats remain to be investigated. Read More

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EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy.

Int J Nanomedicine 2021 26;16:2443-2459. Epub 2021 Mar 26.

Department of Pharmaceutics, State Key Laboratory of Nature Medicines, China Pharmaceutical University, Nanjing, People's Republic of China.

Background: Specific modifications to carriers to achieve targeted delivery of chemotherapeutics into malignant tissues are a critical point for efficient diagnosis and therapy. In this case, bovine serum albumin (BSA) was conjugated with cetuximab-valine-citrulline (vc)-doxorubicin (DOX) to target epidermal growth factor receptor (EGFR) and enable the release of drug in EGFR-overexpressed tumor cells.

Methods: Maleimidocaproyl-valine-citrulline-p-aminobenzylcarbonyl-p-nitrophenol (MC-Val-Cit-PAB-PNP) and DOX were used to synthesize MC-Val-Cit-PAB-DOX, which was further linked with cetuximab to prepare antibody-drug conjugates (ADCs). Read More

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[Effect of MiR-96 on Cell Invasion and Apoptosis in Pediatric Acute Myeloid Leukemia via Regulating MYB].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):439-444

Guizhou Ankang Medical Laboratory Center Co Ltd, Guiyang 550002, Guizhou Province, China,E-mail:

Objective: To analyze the relationship of the expression of transcription factor MYB targeted regulation by miR-96 to cell invasion and apoptosis in pediatric acute myeloid leukemia (AML).

Methods: A total of 65 children with AML in The 928 Hospital of PLA Joint Logistics Support Forces from January 2017 to November 2019 were selected, including 35 cases diagnosed as primary AML and 30 cases as complete remission AML. Thirty children with immune thrombocytopenia were selected as control group. Read More

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miR-30b-5p releases HMGB1 via UBE2D2/KAT2B/HMGB1 pathway to promote pro-inflammatory polarization and recruitment of macrophages.

Atherosclerosis 2021 Feb 26;324:38-45. Epub 2021 Feb 26.

the Second Clinical Medical College, Guangdong Medical University, Dongguan, 523808, China; Chronic Disease Management Center, Cha Shan Hospital, Guangdong Medical University, Dongguan 523382, China; Liaobu Hospital, Guangdong Medical University, Dongguan, Guangdong, 523400, China. Electronic address:

Background And Aims: Oxidized low-density lipoprotein (ox-LDL) is a key risk factor for atherosclerosis, but there are few reports on ox-LDL-mediated inflammation after injury. In this study, we investigated the effects of ox-LDL on endothelial injury and macrophage polarization and recruitment using human aortic endothelial cell line HAEC cells.

Methods: Changes in miRNA levels after ox-LDL treatment were assessed with qRT-PCR. Read More

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February 2021

Microglia Diversity in Healthy and Diseased Brain: Insights from Single-Cell Omics.

Int J Mol Sci 2021 Mar 16;22(6). Epub 2021 Mar 16.

Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093 Warsaw, Poland.

Microglia are the resident immune cells of the central nervous system (CNS) that have distinct ontogeny from other tissue macrophages and play a pivotal role in health and disease. Microglia rapidly react to the changes in their microenvironment. This plasticity is attributed to the ability of microglia to adapt a context-specific phenotype. Read More

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Immune Response Failure in Paucisymptomatic Long-Standing SARS-CoV-2 Spreaders.

Clin Pract 2021 Mar 1;11(1):151-161. Epub 2021 Mar 1.

Department of Internal Medicine, COVID Unit, National Relevance and High Specialization Hospital Trust ARNAS Civico, Di Cristina, Benfratelli, 90127 Palermo, Italy.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. This disease has a spectrum of different clinical pictures with different outcomes. Herein, we report all the data from three paucisymptomatic patients during a hospital stay that might represent a paradigmatic example of the method by which SARS-CoV-2 is shed. Read More

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Phenotypical Characterization and Neurogenic Differentiation of Rabbit Adipose Tissue-Derived Mesenchymal Stem Cells.

Genes (Basel) 2021 Mar 17;12(3). Epub 2021 Mar 17.

Department of Biochemistry and Biotechnology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia.

Although the rabbit is a frequently used biological model, the phenotype of rabbit adipose-derived mesenchymal stem cells (rAT-MSCs) is not well characterized. One of the reasons is the absence of specific anti-rabbit antibodies. The study aimed to characterize rAT-MSCs using flow cytometry and PCR methods, especially digital droplet PCR, which confirmed the expression of selected markers at the mRNA level. Read More

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Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against .

Int J Mol Sci 2021 Mar 27;22(7). Epub 2021 Mar 27.

Pharmacology Department, Faculty of Medicine, Universitat de Valencia, 46010 Valencia, Spain.

Background: In recent years, there has been great interest in developing molecular adjuvants based on antisense oligonucleotides (ASOs) targeting immunosuppressor pathways with inhibitory effects on regulatory T cells (Tregs) to improve immunogenicity and vaccine efficacy. We aim to evaluate the immunostimulating effect of 2'OMe phosphorothioated Foxp3-targeted ASO in an antifungal adjuvanted recombinant vaccine.

Methods: The uptake kinetics of Foxp3 ASO, its cytotoxicity and its ability to deplete Tregs were evaluated in murine splenocytes in vitro. Read More

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Doxycycline-Doped Polymeric Membranes Induced Growth, Differentiation and Expression of Antigenic Phenotype Markers of Osteoblasts.

Polymers (Basel) 2021 Mar 28;13(7). Epub 2021 Mar 28.

Colegio Máximo de Cartuja s/n, Faculty of Dentistry, University of Granada, 18071 Granada, Spain.

Polymeric membranes are employed in guided bone regeneration (GBR) as physical barriers to facilitate bone in-growth. A bioactive and biomimetic membrane with the ability to participate in the healing and regeneration of the bone is necessary. The aim of the present study was to analyze how novel silicon dioxide composite membranes functionalized with zinc or doxycycline can modulate the osteoblasts' proliferation, differentiation, and expression of selected antigenic markers related to immunomodulation. Read More

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Up-regulation of LINC00619 promotes apoptosis and inhibits proliferation, migration and invasion while promoting apoptosis of osteosarcoma cells through inactivation of the HGF-mediated PI3K-Akt signalling pathway.

Epigenetics 2021 Apr 2:1-14. Epub 2021 Apr 2.

Department of Orthopedics, Linyi People's Hospital, Linyi, P.R. China.

This study is performed to evaluate the role of long noncoding RNA (lncRNA) LINC00619 in osteosarcoma through the PI3K-Akt signalling pathway by binding to HGF. Osteosarcoma and osteochondroma tissues from patients were collected. The relationship between lncRNA LINC00619 and HGF was proved by the dual-luciferase reporter gene assay. Read More

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Reporter system architecture affects measurements of noncanonical amino acid incorporation efficiency and fidelity.

Mol Syst Des Eng 2020 Feb 23;5(2):573-588. Epub 2020 Jan 23.

Chemical and Biological Engineering Department, Tufts University, Medford, Massachusetts 02155, United States.

The ability to genetically encode noncanonical amino acids (ncAAs) within proteins supports a growing number of applications ranging from fundamental biological studies to enhancing the properties of biological therapeutics. Currently, our quantitative understanding of ncAA incorporation systems is confounded by the diverse set of characterization and analysis approaches used to quantify ncAA incorporation events. While several effective reporter systems support such measurements, it is not clear how quantitative results from different reporters relate to one another, or which details influence measurements most strongly. Read More

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February 2020

[Practical Basis of Immunohistochemical Research and Multiplexed Immunohistochemistry].

Authors:
Eiichi Sato

Gan To Kagaku Ryoho 2021 Mar;48(3):320-324

Dept. of Pathology, Institute of Medical Science, Tokyo Medical University.

Immunohistochemistry(IHC)is a central tool of modern morphology. IHC is widely used from basic research to diagnostic practice utilizing its advantage in visualizing ability of in situ distribution of target antigens. In order to perform proper immunohistochemical analyses, it is necessary to fully understand the principle of IHC to prepare appropriate samples, to select suitable antibodies, and to apply reasonable method. Read More

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PCSK9 promotes tumor growth by inhibiting tumor cell apoptosis in hepatocellular carcinoma.

Exp Hematol Oncol 2021 Mar 31;10(1):25. Epub 2021 Mar 31.

Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key enzymes in the process of lipid transport, is involved in the disease progression of various types of tumors. This article is to study the role of PCSK9 in the progression of hepatocellular carcinoma (HCC).

Methods: Immunohistochemistry was used to assess the expression of PCSK9 in tumor specimens from 105 HCC patients who underwent curative resection. Read More

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A novel combined bioactivity / chemoactivity holistic approach for the evaluation of dietary supplements.

Food Chem Toxicol 2021 Mar 28:112159. Epub 2021 Mar 28.

Department of Biochemistry-Biotechnology, University of Thessaly, 41500 Larissa, Greece. Electronic address:

There is increased evidence that the excessive production of free radicals in the human body plays a major role in the pathophysiology and development of various diseases, closely associated with oxidative damage. In this frame, the consumption of antioxidant nutrients through food or dietary supplements may prevent free radicals from harming human cells. This work proposes a holistic approach consisting of distinct methodologies, suitable to evaluate the antioxidant and chemoprotective activity of three novel dietary supplements, each one containing active substances with complementary properties. Read More

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Bioreductive Activation of Antitumour Drugs, Doxorubicin and Pirarubicin, Does Not Affect Their Ability to Induce Apoptosis of Sensitive and Multidrug Resistant Leukaemia HL60 Cells.

Anticancer Res 2021 Mar;41(3):1429-1438

Department of Biochemistry, Faculty of Biology, University of Szczecin, Szczecin, Poland.

Background/aim: Clinical significance of antitumour drugs is limited by multidrug resistance (MDR). We examined the effect of bioreductive activation of the anthracyclines, doxorubicin (DOX) and pirarubicin (PIRA), by cytochrome P450 reductase (CPR) on triggering apoptosis of leukaemia HL60 cells and their MDR counterparts.

Materials And Methods: Cell cycle and FAS expression were investigated by flow cytometry. Read More

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Sorafenib Induces Apoptosis and Inhibits NF-κB-mediated Anti-apoptotic and Metastatic Potential in Osteosarcoma Cells.

Anticancer Res 2021 Mar;41(3):1251-1259

Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C.;

Background/aim: Sorafenib, an oral multi-kinase inhibitor, has been shown to improve the outcome of patients with osteosarcoma (OS). However, the anti-OS effect and mechanism of sorafenib has not yet been fully understood. The main purpose of this study was to investigate the effect of sorafenib on apoptotic signaling and Nuclear Factor-κB (NF-κB)-mediated anti-apoptotic and metastatic potential in OS in vitro. Read More

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