Chimeric antigen receptor macrophages targeting c-MET(CAR-M-c-MET) inhibit pancreatic cancer progression and improve cytotoxic chemotherapeutic efficacy.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Macrophages are abundant in the tumor microenvironment, making them an attractive target for therapeutic intervention. While current immunotherapies, including immune checkpoint inhibition (ICI) and chimeric antigen receptor T (CAR-T) cells, have shown limited efficacy in pancreatic cancer, a novel approach involving chimeric antigen receptor macrophages (CAR-M) has, although promising, not been explored in pancreatic cancer.

Protocol for generating human CAR-engineered macrophages by Vpx-containing lentivirus.

Human-derived macrophages are notoriously difficult to infect with HIV-1-based lentiviruses, posing a limitation to the advancement of chimeric antigen receptor macrophage (CAR-M) therapy. Here, we present a protocol for generating human chimeric antigen receptor (CAR)-engineered macrophages using the viral protein Vpx (encoded by the Sooty Mangabey simian immunodeficiency virus [SIV] and HIV-2 lineages) incorporated into the lentivirus vector, which enhances infection efficiency. We describe steps for cell cultivation, lentivirus production, concentration, infection procedures, and efficiency assessments.

Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy.

The high plasticity and long-term persistency make macrophages excellent vehicles for delivering anti-tumor cytokines. Macrophage delivery of chemokines and cytokines shows potential in tumor therapy. TRAIL, a promising anti-tumor cytokine, induces apoptosis in tumor cells with low toxicity to normal cells.

GPC3-targeted CAR-M cells exhibit potent antitumor activity against hepatocellular carcinoma.

Chimeric antigen receptor (CAR)-modified macrophages are a promising treatment for solid tumor. So far the potential effects of CAR-M cell therapy have rarely been investigated in hepatocellular carcinoma (HCC). Glypican-3 (GPC3) is a biomarker for a variety of malignancies, including liver cancer, which is not expressed in most adult tissues.

Structural basis for the inhibition of the HCoV-NL63 main protease M by X77.

Human coronaviruses are a group of pathogens that primarily cause respiratory and intestinal diseases. Infection can easily cause respiratory symptoms, as well as a variety of serious complications. There are several types of human coronaviruses, such as SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, and SARS-CoV-2.

Structural Basis for the Inhibition of SARS-CoV-2 M D48N Mutant by Shikonin and PF-07321332.

Preventing the spread of SARS-CoV-2 and its variants is crucial in the fight against COVID-19. Inhibition of the main protease (M) of SARS-CoV-2 is the key to disrupting viral replication, making M a promising target for therapy. PF-07321332 and shikonin have been identified as effective broad-spectrum inhibitors of SARS-CoV-2 M.

ARV-825 Showed Antitumor Activity against BRD4-NUT Fusion Protein by Targeting the BRD4.

Objective: The bromodomain-containing 4 (BRD4) is a member of the bromodomain and extra terminal domain (BET) family, which is an important epigenetic reader. It is currently a promising oncology target. In some tumors, BET bromodomain inhibitors have demonstrated promising results.

Enhanced infection efficiency and cytotoxicity mediated by vpx-containing lentivirus in chimeric antigen receptor macrophage (CAR-M).

Genetically modified macrophage infusion has been proven to be a novel treatment for cancer. One of the most important processes in macrophage-based therapy is the efficient transfer of genes. HIV-1-derived lentiviruses were widely used as delivery vectors in chimeric antigen receptor T and NK cell construction.

Macrophage-based delivery of anti-fibrotic proteins alleviates bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by chronic, progressive, and fibrotic lung injury. Although remarkable progress has been made toward understanding the pathogenesis of PF, finding more effective treatments for this fatal disease remains a challenge. In this study, we describe an innovative macrophage-based approach to deliver anti-fibrotic protein to the lung and inhibit PF in a mouse model of bleomycin (BLM)-induced lung injury.

Betaine regulates adipogenic and osteogenic differentiation of hAD-MSCs.

Background: With an ageing population, the incidence of bone loss and obesity are increasing. Numerous studies emphasized the multidirectional differentiation ability of mesenchymal stem cells (MSCs), and reported betaine modulated the osteogenic differentiation and adipogenic differentiation of MSCs in vitro. We wondered how betaine affected the differentiation of hAD-MSCs and hUC-MSCs.

Structural basis of main proteases of HCoV-229E bound to inhibitor PF-07304814 and PF-07321332.

PF-07321332 and PF-07304814, inhibitors against SARS-CoV-2 developed by Pfizer, exhibit broad-spectrum inhibitory activity against the main protease (M) from various coronaviruses. Structures of PF-07321332 or PF-07304814 in complex with Ms of various coronaviruses reveal their inhibitory mechanisms against different Ms. However, the structural information on the lower pathogenic coronavirus M with PF-07321332 or PF-07304814 is currently scarce, which hinders our comprehensive understanding of the inhibitory mechanisms of these two inhibitors.

Advance of Mesenchymal Stem Cells in Chronic End-Stage Liver Disease Control.

The chronic liver diseases will slowly develop into liver fibrosis, cirrhosis, and even liver cancer if no proper control is performed with high efficiency. Up to now, the most effective treatment for end-stage liver diseases is liver transplantation. However, liver transplantation has the problems of donor deficiency, low matching rate, surgical complications, high cost, and immune rejection.

Comparison of biological characteristics of human adipose- and umbilical cord- derived mesenchymal stem cells and their effects on delaying the progression of osteoarthritis in a rat model.

Background: The prevalence of osteoarthritis (OA) is constantly increasing with age. Adipose-derived (AD-) and umbilical cord-derived (UC-) mesenchymal stem cells (MSCs) are attractive alternatives in OA therapy and regenerative medicine. However, whether there are differences in the efficacy of MSCs derived from different tissues in the cartilage regeneration, and the frequency of administration of MSCs needs to be further studied.

Crystal structure of SARS-CoV 3C-like protease with baicalein.

The 3C-like protease (M, 3CL) plays a key role in the replication process in coronaviruses (CoVs). The M is an essential enzyme mediates CoVs replication and is a promising target for development of antiviral drugs. Until now, baicalein has been shown the specific activity for SARS-CoV M in vitro experiments.

Simultaneous detection of SARS-CoV-2 and pandemic (H1N1) 2009 virus with real-time isothermal platform.

The recent ongoing outbreak of novel coronavirus SARS-CoV-2 (known as COVID-19) is a severe threat to human health worldwide. By press time, more than 3.3 million people have died from COVID-19, with many countries experiencing peaks in infections and hospitalizations.

Sample-to-answer COVID-19 nucleic acid testing using a low-cost centrifugal microfluidic platform with bead-based signal enhancement and smartphone read-out.

With its origin estimated around December 2019 in Wuhan, China, the ongoing SARS-CoV-2 pandemic is a major global health challenge. The demand for scalable, rapid and sensitive viral diagnostics is thus particularly pressing at present to help contain the rapid spread of infection and prevent overwhelming the capacity of health systems. While high-income countries have managed to rapidly expand diagnostic capacities, such is not the case in resource-limited settings of low- to medium-income countries.

SARS-CoV-2 detection by extraction-free qRT-PCR for massive and rapid COVID-19 diagnosis during a pandemic in Armenia.

COVID-19 pandemic severely impacted the healthcare and economy on a global scale. It is widely recognized that mass testing is an efficient way to contain the spread of SARS-CoV-2 infection as well as aid in the development of informed policies for disease management. However, the current COVID-19 worldwide infection rates increased the demand for rapid and reliable screening of infection.

Colorimetric isothermal nucleic acid detection of SARS-CoV-2 with dye combination.

RT-LAMP detection of SARS-CoV-2 has been demonstrated to be a valuable diagnostic method for the diagnosis of COVID-19, which can rapidly screen carriers of the virus to effectively control the spread of the SARS-CoV-2. Here, we present a combination of dyes for isothermal detection of SARS-CoV-2 as a commercial alternative, with expanded colorimetric spectrum. We compared them with commercial reagents and proved their suitability and sensitivity through clinical RNA samples.

Optimization of scleroglucan production by Sclerotium rolfsii by lowering pH during fermentation via oxalate metabolic pathway manipulation using CRISPR/Cas9.

Background: Sclerotium rolfsii is a potent producer of many secondary metabolites, one of which like scleroglucan is an exopolysaccharide (EPS) appreciated as a multipurpose compound applicable in many industrial fields.

Results: Aspartate transaminase (AAT1) catalyzes the interconversion of aspartate and α-ketoglutarate to glutamate and oxaloacetate. We selected AAT1 in the oxalate metabolic pathway as a target of CRISPR/Cas9.

Direct detection of SARS-CoV-2 using non-commercial RT-LAMP reagents on heat-inactivated samples.

RT-LAMP detection of SARS-CoV-2 has been shown to be a valuable approach to scale up COVID-19 diagnostics and thus contribute to limiting the spread of the disease. Here we present the optimization of highly cost-effective in-house produced enzymes, and we benchmark their performance against commercial alternatives. We explore the compatibility between multiple DNA polymerases with high strand-displacement activity and thermostable reverse transcriptases required for RT-LAMP.

Intraperitoneal injection of Desferal® alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats.

Background: Age-related bone loss plays a vital role in the development of osteoporosis and osteoporotic fracture. Bone marrow stromal cell (BMSC) senescence is highly associated with osteoporosis and limits the application of BMSCs in regenerative medicine. Hypoxia is an essential component for maintaining the normal physiology of BMSCs.

Blockade of Fgfr1 with PD166866 Protects Cartilage from the Catabolic Effects Induced by Interleukin-1β: A Genome-Wide Expression Profiles Analysis.

Objective: Previously we showed that genetic deletion of Fgfr1 in chondrocytes protected mice from progression of osteoarthritis (OA). The aim of this study is to evaluate the effect of PD166866, a potent selective inhibitor of Fgfr1, on cartilage degeneration induced by interleukin-1β (IL-1β) and to clarify underlying global gene expression pattern.

Design: Cartilage explants and primary rat chondrocytes were stimulated with IL-1β to establish an inflammatory OA model.