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Article
Clinical Neurology
Laura Silva et al.
Summary: The neuroprotective effects of betulinic hydroxamate (BAH), a novel B55 alpha/PP2A activator, were studied in a rat model of neonatal hypoxic-ischemic brain damage (HIBD). BAH reduced brain damage volume and cell death, prevented motor and working memory deficits, and showed a robust protective effect on myelination. BAH also modulated excitotoxicity, oxidative stress, and inflammation. The therapeutic window of BAH was broad, with most neuroprotective effects still present even with delayed administration.
TRANSLATIONAL STROKE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Xinai Liao et al.
Summary: Patients with AML have poor prognoses due to heterogeneity and complex tumor microenvironment. This study analyzed the m(6)A modification features of 177 AML patients and identified three distinct m(6)A modification patterns related to biological functions, TME characteristics, and clinical outcomes. A risk score based on six m(6)A regulators was constructed and validated as an independent prognostic factor for AML. Four m(6)A regulators were found to be associated with AML survival and immune checkpoint inhibitor treatments. Understanding the m(6)A modification pattern can enhance our knowledge of AML and aid in the development of prognosis indicators and immunotherapeutic strategies.
Article
Immunology
Ya-nan Zhu et al.
Summary: ATRA promotes polarization of M2 macrophages by activating the p38MAPK/STAT6 signaling pathway.
IMMUNOLOGICAL INVESTIGATIONS
(2023)
Article
Engineering, Biomedical
Linghao Xiao et al.
Summary: Previous research has shown that octacalcium phosphate (OCP) enhances macrophage accumulation and modifies the initial inflammatory response. This study investigates the behavior of macrophages and their role in bone regeneration during the early inflammatory stage of OCP-mediated osteogenesis. The findings suggest that OCP not only regulates immune function through macrophage polarization and secretion profile, but also positively impacts osteogenesis.
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
(2023)
Article
Oncology
Kewen He et al.
Summary: Various factors contribute to limited clinical response to radiotherapy and immunotherapy in metastatic non-small cell lung cancer, including the recruitment of suppressive immune cells such as M2 tumor-associated macrophages. Targeting STAT6 using ASO along with hypofractionated radiotherapy was found to inhibit tumor growth, decrease metastasis, and enhance antitumor responses, providing a preclinical rationale for alternative therapeutic approaches in immune-resistant NSCLC patients.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Engineering, Biomedical
Lang Chen et al.
Summary: Researchers developed an injectable, self-healing, adhesive hydrogel that combines Stromal Cell-Derived Factor-1 alpha (SDF-1 alpha) and M2 macrophage derived exosomes (M2D-Exos). This hydrogel enhanced proliferation and migration of human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells, promoting osteogenesis and angiogenesis both in vivo and in vitro. It provides a new modality for accelerating bone repair by coupling osteogenesis, angiogenesis, and resisting infection at all stages.
BIOACTIVE MATERIALS
(2023)
Article
Engineering, Biomedical
Hyosuk Kim et al.
Summary: The highly immunosuppressive tumor microenvironment with protumoral immune cells accelerates malignant transformation and treatment resistance. Tumor-associated macrophages (TAMs), as the predominant immune cells in tumors, play a crucial role in regulating the immunosuppressive tumor microenvironment. This study explores an exosome-guided direct reprogramming of tumor-supportive M2-polarized TAMs into tumor-attacking M1-type macrophages, potentially enhancing antitumor immunity.
BIOACTIVE MATERIALS
(2023)
Article
Medicine, Research & Experimental
Maria Eugenia Prados et al.
Summary: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, with neuroinflammation and brain-blood barrier (BBB) disruption playing critical roles in its pathogenesis. In this study, the potential therapeutic effects of VCE-005.1, a betulinic acid hydroxamate, were investigated in vitro and in a TBI mouse model. The results demonstrate that VCE-005.1 stabilizes HIF-1 alpha, enhances TJ protein expression, promotes angiogenesis, improves locomotor coordination, preserves BBB integrity, reduces immune cells infiltration, recovers AMPK expression, and decreases neuronal cell apoptosis in the TBI model, highlighting its multitarget anti-inflammatory and neuroprotective properties.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biophysics
Ezgi Tan et al.
Summary: This study reported an investigation on the in-vitro anticancer activity of ceranib-2 (Cer), betulinic acid (BA), and the combination of betulinic acid and ceranib-2 (BA-Cer) against PC-3 prostate cancer cells. A suitable nanocarrier was designed using a novel Zn:MnO2 nanocomposite (NCs) and gallic acid (GA)-polylactic acid (PLA)-Alginate polymeric shell, which exhibited good stability and enhanced drug loading and release capacity. The BA-Cer/Zn:MnO2@GA-PLA-Alginate nanocarrier showed promise as an imaging and treatment agent due to its magnetic properties and had potential in prostate cancer therapy.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Pharmacology & Pharmacy
Mohammad Souri et al.
Summary: This study introduces an efficient nanosized drug delivery system with programmable size changes, which improves the accumulation of drug-carrying nanoparticles in tumors and achieves higher penetration depths. Reducing the size of nanoparticles leads to higher cell death rate and longer inhibition of tumor growth. This drug delivery system shows great promise in clinical applications.
Article
Biochemistry & Molecular Biology
Chunlong Zhang et al.
Summary: Abnormal DNA methylation can modulate the tumor immune microenvironment and regulate the expression of immune-related genes. DNA hypomethylation is involved in immunity, carcinogenesis, and immune infiltration. The study also identified molecular subtypes of kidney renal clear cell carcinoma based on DNA methylation patterns, major histocompatibility complex, cytolytic activity, cytotoxic T lymphocyte response, and tumor mutation burden. Furthermore, DNA methylation affects the expression of exhaustion-related markers in the tumor immune microenvironment.
Article
Immunology
Qiujie Luo et al.
Summary: This study investigated the role of TREM2 in macrophage regulation and its potential therapeutic implications for pulmonary fibrosis. The results showed that TREM2 insufficiency could inhibit pulmonary fibrosis and M2 macrophage polarization through the activation of the STAT6 pathway and regulation of fibrotic factors.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Oncology
Puran Zhang et al.
Summary: In gastric cancer, targeting C5aR1(+) TAMs may enhance the therapeutic response of PD-1 blockade by reducing immunosuppression and improving CD8(+) T cell immune response.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Jiaying Cao et al.
Summary: Under conditions of oxygen sufficiency, tumor cells utilize glycolysis to supply themselves with energy, leading to rapid proliferation, metastasis, and drug resistance. Tumor-associated macrophages (TAMs), which are immune-related cells in the tumor microenvironment (TME), are influenced by altered glycolysis levels, affecting their polarization and function. The interaction between glycolysis changes in tumor cells and other immune-associated cells in the TME also impacts TAMs.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Takashi Ito et al.
Summary: This study investigated the effects of pentacyclic triterpenoids, including betulinic acid (BA), on the cellular proliferation and senescence of normal human dermal fibroblasts (NHDFs). BA treatment increased the proliferation of young fibroblasts and reduced the proportion of senescent cells in high-passage NHDFs. The downregulation of interferon (IFN)-inducible genes, including IFIT1, IFITM1, IFI6, MX1, and OAS2, by BA suggested the suppression of the type I IFN signaling pathway. BA also downregulated the expression of the IRF9 transcriptional factor downstream of the type 1 IFN signaling pathway.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Plant Sciences
Li Tao et al.
Summary: This study aimed to investigate the chemopotentiating effects and underlying mechanisms of betulinic acid, a primary therapeutic triterpene of C. orbiculatus, in combination with gemcitabine chemotherapy for pancreatic cancer and non-small cell lung cancer. The results showed that the combination therapy of betulinic acid and gemcitabine significantly promoted apoptosis and DNA double-strand breaks in cancer cells, and inhibited tumor growth by reducing Chk1 expression.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Immunology
Michael A. Gonzalez et al.
Summary: Tracking phagocytic tumor-associated myeloid cells in a novel lung tumor model reveals important responses to neoplastic cell engulfment, including elevated oxidative phosphorylation and immune suppression. The phagocytic signature is also present in myeloid cells from human tumors. Expression of oxidative phosphorylation genes is associated with worse clinical outcome in human lung cancer. This study highlights the importance of phagocytosis in shaping tumor-associated macrophage phenotypes and identifies a distinct phagocytic TAM state that promotes tumor growth.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Buyun Dang et al.
Summary: This study demonstrates the important role of IL-4-primed M2 macrophages in inflammation resolution and wound healing. The metabolic divergence between canonical M2 and non-canonical proinflammatory-prone M2INF macrophages occurs after the IL-4Ra/Stat6 axis, and glycolysis supports the proinflammatory phenotype of M2INF macrophages. The findings also suggest that IL-4 induction of M2INF macrophages can confer a survival advantage against bacterial infection in vivo.
Article
Medicine, General & Internal
Zhao Zhan et al.
Summary: This study investigated the role of the high endothelial venules/tertiary lymphoid structures (HEV/TLS) in colorectal cancer (CRC) and found that it is associated with a favorable prognosis and the anti-tumor immune microenvironment.
ANNALS OF MEDICINE
(2023)
Article
Plant Sciences
Ya-rong Lin et al.
Summary: This study found that koumine, the main component in Gelsemium elegans Benth., can regulate macrophage polarization in patients with rheumatoid arthritis through the PI3K/AKT signaling pathway. These findings provide a theoretical and scientific basis for the potential clinical application of koumine in the treatment of rheumatoid arthritis.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Engineering, Biomedical
Ye Yuan et al.
Summary: This study designed a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel that can enhance angiogenesis, regulate inflammation, and inhibit muscle necrosis, to treat lower-limb ischemic diseases.
BIOACTIVE MATERIALS
(2023)
Article
Cell Biology
Feng Hua et al.
Summary: Neurons secrete substance P in response to spinal surgery, promoting macrophage differentiation in epidural fibrosis. The study found that sphingolipids were released by dorsal root ganglion neurons and infiltrating macrophages in the wound area. Substance P was shown to promote M2 macrophage differentiation through sphingomyelin synthase 2 and neutrophil extracellular traps, and blocking substance P alleviated epidural fibrosis.
NEURAL REGENERATION RESEARCH
(2023)
Article
Cell Biology
Jia-Gui Huang et al.
Summary: In this study, it was found that M2 macrophages regulate fibrotic scar formation after cerebral ischemia injury through IL4/sonic hedgehog/transforming growth factor beta 1 signaling, suggesting a potential therapeutic target for ischemic stroke.
NEURAL REGENERATION RESEARCH
(2023)
