Within the cardiovascular system, growth-related peptide (GRP) elevates the expression of intercellular adhesion molecule 1 (ICAM-1) and stimulates the production of vascular cell adhesion molecule-1 (VCAM-1). Cardiovascular diseases, including myocardial infarction, result from GRP's stimulation of ERK1/2, MAPK, and AKT. Signal transduction within the central nervous system, orchestrated by the GRP/GRPR axis, is crucial for emotional responses, social interactions, and memory formation. In numerous cancers, including lung, cervical, colorectal, renal cell, and head and neck squamous cell carcinomas, the GRP/GRPR axis is found to be elevated. GRP's mitogenic properties are evident in a diverse array of tumour cell lines. In the field of early tumor diagnosis, pro-gastrin-releasing peptide (ProGRP), a precursor, is poised to play an essential role as a novel marker. Drug development frequently targets GPCRs, yet their precise roles within various diseases remain elusive, and their contributions to disease progression lack comprehensive investigation and summary. Previous research findings form the basis of this review, which outlines the pathophysiological processes discussed above. The GRP/GRPR axis is potentially a viable therapeutic target across several disease states, thus demonstrating the critical nature of research on this signaling axis.
The growth, invasion, and metastasis of cancer cells are usually facilitated by metabolic adjustments. Reprogramming cellular energy metabolism within the cell is presently a central theme in the ongoing exploration of cancer. In contrast to the long-held view of aerobic glycolysis (Warburg effect) as the primary energy source for cancer cells, growing evidence suggests an important role for oxidative phosphorylation (OXPHOS) in some cancers. Women who manifest metabolic syndrome (MetS), including obesity, hyperglycemia, dyslipidemia, and hypertension, often have a higher propensity to develop endometrial carcinoma (EC), underscoring the strong connection between metabolic factors and EC. Interestingly, metabolic preferences exhibit diversity among EC cell types, notably within cancer stem cells and chemotherapy-resistant cells. Glycolysis presently holds the status of the central energy provider in EC cells; conversely, OXPHOS is lessened or impaired. In addition, agents that are directed at the glycolysis and/or OXPHOS pathways can effectively halt the growth of tumor cells and boost the response to chemotherapy. AZD8797 The combined effect of metformin and weight control results in a reduced occurrence of EC, as well as improved prognoses for EC patients. This review scrutinizes the current, profound understanding of the metabolic underpinnings of EC, providing insightful updates on the development of novel therapies for combining energy metabolism modulation with chemotherapy, particularly in overcoming resistance to conventional EC treatments.
The human malignant tumor, glioblastoma (GBM), presents a significant challenge due to its low survival rate and high recurrence. Research indicates that Angelicin, an active furanocoumarin compound, demonstrates the possibility of inhibiting the growth of different types of cancerous tumors. Still, the impact of angelicin on GBM cells and its underlying mechanism are not fully elucidated. The results of our study indicate that angelicin inhibited GBM cell proliferation, achieving this by causing a cell cycle arrest at the G1 phase and also inhibiting their migratory behavior in laboratory experiments. Our mechanical findings indicate that angelicin decreased YAP expression, limited YAP's nuclear entry, and suppressed -catenin's production. Subsequently, YAP's elevated expression partially reversed the inhibitory effect of angelicin on GBM cells, within the confines of an in vitro environment. In the end, angelicin was shown to inhibit the development of tumors and to reduce the amount of YAP protein expressed, as observed in subcutaneous xenograft models of GBM in nude mice and in syngeneic intracranial orthotopic models of GBM in C57BL/6 mice. The integrated analysis of our results highlights angelicin, a natural product, as a potential anticancer agent for glioblastoma (GBM), acting through the YAP signaling pathway.
Life-threatening conditions, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are frequently observed in COVID-19 patients. Xuanfei Baidu Decoction (XFBD), a recommended first-line traditional Chinese medicine (TCM) formula, is a therapeutic strategy for COVID-19 patients. Pharmacological studies of XFBD and its active constituents have revealed their roles and mechanisms in mitigating inflammation and infections, supported by data from multiple model systems, which support its clinical utility. The PD-1/IL17A signaling pathway was identified in our previous work as the mechanism by which XFBD restricted the infiltration of macrophages and neutrophils. Although this is the case, the subsequent biological developments are not entirely understood. The hypothesis presented here posits a regulatory mechanism of XFBD on neutrophil-mediated immune responses, encompassing the generation of neutrophil extracellular traps (NETs) and platelet-neutrophil aggregates (PNAs) after XFBD treatment in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Initially, the mechanism responsible for XFBD's regulation of NET formation was described, centering on the CXCL2/CXCR2 pathway. Our findings comprehensively demonstrated a sequential immune response in XFBD, following the inhibition of neutrophil infiltration. This also highlighted the potential of targeting neutrophils in XFBD therapy to improve ALI during clinical treatment.
Characterized by silicon nodules and diffuse pulmonary fibrosis, silicosis is a devastating form of interstitial lung disease. A significant challenge in treating this disease remains the complicated pathogenesis, leading to currently inefficient therapies. Silicosis resulted in a downregulation of hepatocyte growth factor (HGF), a molecule highly expressed in hepatocytes and known for its anti-fibrotic and anti-apoptotic actions. The upregulation of transforming growth factor-beta (TGF-), a further pathological molecule, was observed to worsen the severity and accelerate the development of silicosis. Synergistic reduction of silicosis fibrosis was achieved by the concurrent application of AAV-expressed HGF, targeted to pulmonary capillaries, and SB431542, an inhibitor of the TGF-β signaling pathway. In vivo studies on silicosis mice subjected to tracheal silica administration showed that the simultaneous application of HGF and SB431542 significantly mitigated fibrosis, contrasting with separate treatment. The remarkable efficacy was principally due to an impressive reduction in lung tissue ferroptosis. In our view, AAV9-HGF and SB431542 synergistically provide an alternative treatment option for silicosis fibrosis, focusing on the pulmonary capillary network.
Current cytotoxic and targeted therapies prove to be of limited help to advanced ovarian cancer (OC) patients who have undergone debulking surgery. Hence, there is an immediate need for innovative therapeutic strategies. Immunotherapy's remarkable potential is evident in the realm of tumor treatment, especially in the context of tumor vaccine development. AZD8797 The research objective was to investigate the immunological effects of cancer stem cell (CSC) vaccines upon ovarian cancer (OC). Cancer stem-like cells (CSCs), specifically those expressing CD44 and CD117, were isolated from human OC HO8910 and SKOV3 cells using magnetic cell sorting; a no-serum sphere culture was used to identify cancer stem-like cells within murine OC ID8 cells. The freezing and thawing of CSCs led to vaccine preparation, these vaccines were injected into mice, followed by a challenge with distinct OC cell populations. In vivo studies of cancer stem cell (CSC) immunization revealed that these vaccines elicited substantial immune responses to autologous tumor antigens. Consequently, vaccinated mice exhibited marked inhibition of tumor growth, increased survival durations, and diminished CSC counts in ovarian cancer (OC) tissues, in comparison to control mice lacking CSC vaccination. Immunocyte in vitro cytotoxicity assays on SKOV3, HO8910, and ID8 cells revealed a marked killing effectiveness compared to the control groups. Remarkably, the effectiveness against tumors was considerably reduced, coupled with a decrease in mucin-1 expression levels within cancer stem cell vaccines, achieved through the use of small interfering RNA. In conclusion, the investigation's results furnished compelling evidence enhancing our comprehension of CSC vaccine immunogenicity and its efficacy against OC, particularly concerning the pivotal role of the dominant antigen mucin-1. An immunotherapeutic approach against ovarian cancer is potentially achievable by transforming the CSC vaccine.
As a natural flavonoid compound, chrysin offers both antioxidant and neuroprotective advantages. Increased oxidative stress in the hippocampal CA1 region, coupled with disruptions in the homeostasis of transition elements like iron (Fe), copper (Cu), and zinc (Zn), is closely linked to cerebral ischemia reperfusion (CIR). AZD8797 This study investigated the antioxidant and neuroprotective properties of chrysin, focusing on a transient middle cerebral artery occlusion (tMCAO) model in rats. In the experimental design, groups were formed, encompassing a sham group, a model group, a chrysin-treated group (500 mg/kg), a Ginaton-treated group (216 mg/kg), a combined DMOG (200 mg/kg) and chrysin group, and a DMOG (200 mg/kg) group. Following a standardized protocol, each group of rats experienced behavioral assessments, histological staining, biochemical kit-based detection, and molecular biological analyses. In tMCAO rats, chrysin's action encompassed the inhibition of oxidative stress, the reduction of rising transition metal levels, and the regulation of transporter proteins responsible for transition metal transport. Hypoxia-inducible factor-1 subunit alpha (HIF-1), activated by DMOG, reversed the neuroprotective and antioxidant functions of chrysin, escalating levels of transition elements.