Diabetic wound-healing difficulties are common for patients with diabetes. Compared to normal wound healing processes, the hyperglycaemic environment in diabetic wounds increases the proportion of M1 macrophages significantly, thereby prolonging the inflammatory phase of wound healing. Consequently, treatment approaches targeting macrophages are gaining increasing attention in both research and clinical practice.
View Article and Find Full Text PDFBackground: To delve into the precise mechanisms by which 6-gingerol ameliorates lipid metabolism disorders in skeletal muscle.
Methods: The level of triglycerides (TG) was used to evaluate lipid deposition. In skeletal muscle, transmission electron microscopy (TEM) was employed to observe mitochondrial morphology.
Aims: We intend to elucidate the alterations of cerebral networks in patients with insular glioma-related epilepsy (GRE) based on resting-state functional magnetic resonance images.
Methods: We collected 62 insular glioma patients, who were subsequently categorized into glioma-related epilepsy (GRE) and glioma with no epilepsy (GnE) groups, and recruited 16 healthy individuals matched to the patient's age and gender to form the healthy control (HC) group. Graph theoretical analysis was applied to reveal differences in sensorimotor, default mode, visual, and executive networks among different subgroups.
Ectopic lipid deposition (ELD) and mitochondrial dysfunction are common causes of metabolic disorders in humans. Consuming too much fructose can result in mitochondrial dysfunction and metabolic disorders. 6-Gingerol, the main component of ginger (Zingiber officinale Roscoe), has been proven to alleviate metabolic disorders.
View Article and Find Full Text PDFBackground: Type 2 diabetes mellitus (T2DM) is closely linked to metabolic syndrome, characterised by insulin resistance, hyperglycaemia, abnormal lipid metabolism, and chronic inflammation. Diabetic ulcers (DUs) comprise consequential complications that arise as a result of T2DM. To investigate, db/db mice were used for the disease model.
View Article and Find Full Text PDFDiabetic patients often experience long-term risks due to chronic inflammation and delayed re-epithelialization during impaired wound healing. Although the severity of this condition is well known, the treatment options for diabetic wounds are limited. Rhubarb charcoal, a well-known traditional Chinese medicine, has been used to treat skin wounds for thousands of years.
View Article and Find Full Text PDFBackground & Aims: Tumor-associated macrophages (TAMs) are indispensable in the hepatocellular carcinoma (HCC) tumor microenvironment. Xanthine oxidoreductase (XOR), also known as xanthine dehydrogenase (XDH), participates in purine metabolism, uric acid production, and macrophage polarization to a pro-inflammatory phenotype. However, the role of XOR in HCC-associated TAMs is unclear.
View Article and Find Full Text PDFPrevious studies show that astragaloside IV (ASIV) has anti-renal fibrosis effects. However, its mechanism remains elusive. In this study, we investigated the anti-fibrosis mechanisms of ASIV on chronic kidney disease (CKD) in vivo and in vitro.
View Article and Find Full Text PDF6-Gingerol, one of the major pharmacologically active ingredients extracted from ginger, has been reported experimentally to exert hepatic protection in non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanism remains largely elusive. RNA sequencing indicated the significant involvement of the AMPK signaling pathway in 6-gingerol-induced alleviation of NAFLD in vivo.
View Article and Find Full Text PDFObesity-induced chronic liver inflammation is a hallmark of nonalcoholic steatohepatitis (NASH)-an aggressive form of nonalcoholic fatty liver disease. However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver. Here, we show that the macrophage phagocytic receptor TREM2, induced by hepatocyte-derived sphingosine-1-phosphate, was required for efferocytosis of lipid-laden apoptotic hepatocytes and thereby maintained liver immune homeostasis.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) is one of the most fatal tumours worldwide and has a high recurrence rate. Nevertheless, the mechanism of HCC genesis remains partly unexplored, while the efficiency of HCC treatments remains limited. The present study analysed the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1) in tumour-infiltrating natural killer (NK) cells derived from both human patients with HCC and tumour-bearing mouse models, as well as the features of NR4A1 and NR4A1 NK cells.
View Article and Find Full Text PDFThe specification of the αβ/γδ lineage and the maturation of medullary thymic epithelial cells (mTECs) coordinate central tolerance to self-antigens. However, the mechanisms underlying this biological process remain poorly clarified. Here, we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation, promoted thymic IL-17A-producing γδ T-cell (Tγδ17) lineage commitment, and led to the development of fatal autoimmune hepatitis (AIH) via different mechanisms.
View Article and Find Full Text PDFChemoimmunotherapy has shown great potential to activate an immune response, but the immunosuppressive microenvironment associated with T cell exhaustion remains a challenge in cancer therapy. The proper immune-modulatory strategy to provoke a robust immune response is to simultaneously regulate T-cell exhaustion and infiltration. Here, a new kind of carrier-free nanoparticle is developed to simultaneously deliver chemotherapeutic drug (doxorubicin, DOX), cytolytic peptide (melittin, MPI), and anti-TOX small interfering RNA (thymocyte selection-associated high mobility group box protein, TOX) using a fluorinated prodrug strategy.
View Article and Find Full Text PDFCancer-testis (CT) genes participate in the initiation and progression of cancer, but the role of CT-associated long non-coding RNAs (CT-lncRNAs) in hepatocellular carcinoma (HCC) is still elusive. Here, we discovered a conserved CT-lncRNA, named lnc-CTHCC, which was highly expressed in the testes and HCC. A lnc-CTHCC-knockout (KO) mouse model further confirmed that the global loss of lnc-CTHCC inhibited the occurrence and development of HCC.
View Article and Find Full Text PDFObjectives: Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue.
View Article and Find Full Text PDFBackground & Aims: Non-alcoholic steatohepatitis (NASH) is associated with the dysregulation of lipid metabolism and hepatic inflammation. The causal mechanism underlying NASH is not fully elucidated. This study investigated the role of β-Arrestin1 (ARRB1) in the progression of NASH.
View Article and Find Full Text PDFBackground & Aims: The thymocyte selection-associated high mobility group box protein (TOX) plays a vital role in T cell development and differentiation, however, its role in T cell exhaustion was unexplored. Here, we aim to investigate the role of TOX in regulating the antitumor effect of CD8 T cells in hepatocellular carcinoma.
Methods: Fully functional, partially and severely exhausted tumor-infiltrating CD8 T cells were sorted by flow cytometry and subjected to transcriptome sequencing analysis.
Hepatic ischemia-reperfusion (I/R) injury is a major challenge in liver resection and transplantation surgeries. Previous studies have revealed that guanine nucleotide-binding protein G(i)α2 (GNAI2) was involved in the progression of myocardial and cerebral I/R injury, but the role and function of GNAI2 in hepatic I/R have not been elucidated. The hepatocyte-specific GNAI2 knockout (GNAI2) mice were generated and subjected to hepatic I/R injury.
View Article and Find Full Text PDFBackground: Previous studies suggested that diverse cells in cancer microenvironment can interact with CD8+ T cells via exosomes. We designed this study to explore the potential interaction between exhausted CD8+ T cells and normal CD8+ T cells via exosome.
Methods: Fluorescence activated cell sorting was used to get PD1+TIM3+/PD1-TIM3-CD8+ T cells.
Immunotherapy has emerged as one of the most promising therapeutic strategies in cancer. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as an RNA-guided genome editing technology, is triggering a revolutionary change in cancer immunotherapy. With its versatility and ease of use, CRISPR-Cas9 can be implemented to fuel the production of therapeutic immune cells, such as construction of chimeric antigen receptor T (CAR-T) cells and programmed cell death protein 1 knockout.
View Article and Find Full Text PDFBackground: Several recent studies published have suggested that T cell exhaustion exists both in chronic infection and cancer. However, to date, few studies have investigated their differences. Here we designed this study to explore the genetic and phenotypic difference in CD8 T cell exhaustion between chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFThe imbalance of immune status in cancer microenvironment plays an important role in the development and progression of cancer. Immunotherapy based on this has become an important field of cancer research in recent years. Many studies on long noncoding RNA (lncRNA) in cancer have focus on its regulation in cancer development and metastasis.
View Article and Find Full Text PDFBrief Funct Genomics
March 2019
Immunotherapies have emerged as the most promising area in cancer treatments in recent years. CD8+ T cells, as one of the primary effector cells of anticancer immunity, however, when infiltrating in cancer tissues, are generally in dysfunctional states termed T-cell exhaustion. Exhausted CD8+ T cells are characterized by impaired activity and proliferative ability, increased apoptotic rate and reduced production of effector cytokines.
View Article and Find Full Text PDFIncreasing evidence shows that the anti-tumor functions of tumor-infiltrating T lymphocytes (TILs) were inhibited significantly, but the underlying mechanisms remain not fully understood. In this study, we found that 14-3-3ζ expression was up-regulated in hepatocellular carcinoma (HCC) cells and in TILs. TILs with 14-3-3ζ high-expression (14-3-3ζ) exhibited impaired activation (CD69), proliferation (Ki67) and anti-tumor functions compared to 14-3-3ζ low expression (14-3-3ζ) TILs.
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