Background
Junctional adhesion molecule 2 (JAM2) plays a pivotal role in various biological processes, including proliferation, metastasis and angiogenesis, contributing to tumor progression. While ...previous studies have highlighted the polarizing functions of JAM2 in different cancer types, its specific role in lung adenocarcinoma (LUAD) remains unclear.
Methods
In this study, we harnessed multiple public databases to analyze the expression and prognostic significance of JAM2 in LUAD. Using the Linkedomics database, Matescape database and R package, we explored the associated genes, the potential biological functions and the impact of JAM2 on the tumor microenvironment. Our findings from public databases were further validated using real‐time quantitative PCR, western blot and immunohistochemistry. Additionally, in vitro experiments were conducted to assess the influence of JAM2 on LUAD cell proliferation, invasion, migration, apoptosis and epithelial–mesenchymal transition. Furthermore, we established a xenograft model to investigate the in vivo effects of JAM2 on tumorigenesis.
Results
Our results revealed a significant downregulation of JAM2 in LUAD, and patients with low JAM2 expression exhibited unfavorable overall survival outcomes. Functional enrichment analysis indicated that JAM2 may be associated with processes such as cell adhesion, extracellular matrix, cell junctions and regulation of proliferation. Notably, increased JAM2 expression correlated with higher tumor microenvironment scores and reduced immune cell abundance. Furthermore, overexpression of JAM2 induced apoptosis, suppressed tumor proliferation and exhibited potential inhibitory effects on tumor invasion and migration through the modulation of epithelial–mesenchymal transition. Additionally, in vivo experiments confirmed that JAM2 overexpression led to a reduction in tumor growth.
Conclusion
Overall, our study highlights the clinical significance of low JAM2 expression as a predictor of poor prognosis in LUAD patients. Moreover, JAM2 was found to exert inhibitory effects on various aspects of tumor progression. Consequently, JAM2 emerges as a promising prognostic biomarker and a potential therapeutic target for LUAD patients.
In this study, the prognostic value and potential function of JAM2 in lung adenocarcinoma were analyzed by combining bioinformatics analysis, in vitro and in vivo experiments, and clinical specimens.
Lipid metabolism is a complex physiological process that is involved in nutrient adjustment, hormone regulation, and homeostasis. An unhealthy lifestyle and chronic nutrient overload can cause lipid ...metabolism disorders, which may lead to serious lipid-related diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes mellitus (T2DM). Therefore, tools for preventing dysfunctional lipid metabolism are urgently needed. The transcription factor forkhead box protein O1 (FOXO1) is involved in lipid metabolism and plays a critical role in the development of lipid-related diseases. In this review, we provide a global perspective on the role of FOXO1 in lipid metabolism and lipid-related diseases. The information included here may be useful for the design of future studies and advancing investigations of FOXO1 as a therapeutic target.
Fibrosis is a common process characterized by excessive extracellular matrix (ECM) accumulation after inflammatory injury, which is also a crucial cause of aging. The process of fibrosis is involved ...in the pathogenesis of most diseases of the heart, liver, kidney, lung, and other organs/tissues. However, there are no effective therapies for this pathological alteration. Annually, fibrosis represents a huge financial burden for the USA and the world. 5'-AMP-activated protein kinase (AMPK) is a pivotal energy sensor that alleviates or delays the process of fibrogenesis. In this review, we first present basic background information on AMPK and fibrogenesis and describe the protective roles of AMPK in three fibrogenic phases. Second, we analyze the protective action of AMPK during fibrosis in myocardial, hepatic, renal, pulmonary, and other organs/tissues. Third, we present a comprehensive discussion of AMPK during fibrosis and draw a conclusion. This review highlights recent advances, vital for basic research and clinical drug design, in the regulation of AMPK during fibrosis.
Silent information regulator 1 (SIRT1), a type of histone deacetylase, is a highly effective therapeutic target for protection against ischemia reperfusion (IR) injury (IRI). Previous studies showed ...that melatonin preserves SIRT1 expression in neuronal cells of newborn rats after hypoxia–ischemia. However, the definite role of SIRT1 in the protective effect of melatonin against cerebral IRI in adult has not been explored. In this study, the brain of adult mice was subjected to IRI. Prior to this procedure, the mice were given intraperitoneal with or without the SIRT1 inhibitor, EX527. Melatonin conferred a cerebral‐protective effect, as shown by reduced infarct volume, lowered brain edema, and increased neurological scores. The melatonin‐induced upregulation of SIRT1 was also associated with an increase in the anti‐apoptotic factor, Bcl2, and a reduction in the pro‐apoptotic factor Bax. Moreover, melatonin resulted in a well‐preserved mitochondrial membrane potential, mitochondrial Complex I activity, and mitochondrial cytochrome c level while it reduced cytosolic cytochrome c level. However, the melatonin‐elevated mitochondrial function was reversed by EX527 treatment. In summary, our results demonstrate that melatonin treatment attenuates cerebral IRI by reducing IR‐induced mitochondrial dysfunction through the activation of SIRT1 signaling.
Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide‐binding oligomerization domain‐like receptor family ...pyrin domain‐containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti‐inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood–brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), cleaved caspase‐1, interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6); these changes were also associated with an increase in the anti‐apoptotic factor (Bcl2) and reduction in the pro‐apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome‐associated apoptosis.
A fundamental element of acute lung injury (ALI) is the inflammatory response, which can affect the entire respiratory system, including the respiratory tract and alveoli. Berberine has gained ...attention because of its anti‐inflammatory effects. Nuclear factor‐erythroid 2‐related factor 2 (Nrf2) and endoplasmic reticulum (ER) stress are involved in lung injury. Nrf2 also acts as a protein kinase‐like ER kinase (PERK) substrate in heart disease. Therefore, this study investigated the effect of berberine against lipopolysaccharide (LPS)‐induced ALI and the role of the PERK‐mediated Nrf2/HO‐1 signaling axis. Berberine promoted Nrf2 nuclear translocation and phosphorylation in vitro. After LPS stimulation, this effect was further enhanced, whereas inflammatory factor (IL‐6 and IL‐8) release and reactive oxygen species generation were significantly decreased. Berberine effectively alleviated lung injury by reducing lung edema and neutrophil infiltration. Berberine also significantly reduced histopathological inflammatory changes via inhibition of ER stress and activation of Nrf2 signaling. Thapsigargin‐induced ER stress and small interference RNA (siRNA)‐mediated Nrf2 inhibition abrogated the protective effects of berberine in vitro, whereas siRNA‐mediated suppression of ER stress and sulforaphane‐induced Nrf2 activation further improved those effects. Importantly, ER stress induction led to Nrf2 activation, whereas PERK depletion partly reduced the level of Nrf2 phosphorylation and translocation in LPS‐induced cells. Therefore, berberine inhibits LPS‐induced ALI through the PERK‐mediated Nrf2/HO‐1 signaling axis.
Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling. This signaling is typically generated at cell ...surface receptors, the activation of which results in the translocation of STATs to the nucleus. STATs are involved in biological events as diverse as embryonic development, programmed cell death, organogenesis, innate immunity, adaptive immunity and cell growth regulation in organisms ranging from slime molds to insects to humans. Numerous studies have demonstrated the activation of STAT3 in neurological diseases, particularly in cerebral ischemic and hemorrhagic stroke. Additionally, STAT3 has also been reported to play a critical role in neuroprotective therapies. In light of the pleiotropic effects of STAT3 on the nervous system, we present the elaborate network of roles that STAT3 plays in cerebral ischemia and hemorrhage in this review. First, we introduce basic knowledge regarding STAT3 and briefly summarize the activation, inactivation, and regulation of the STAT3 pathway. Next, we describe the activation of STAT3 following cerebral ischemia and hemorrhage. Subsequently, we discuss the physiopathological roles of STAT3 in cerebral ischemia and hemorrhage. Moreover, we summarize several significant cerebral ischemic and hemorrhagic stroke treatments that target the STAT3 signaling pathway, including pharmacological and physical therapies. Finally, we highlight research progress on STAT3 in stroke. This review presents the important roles of STAT3 in the nervous system and may contribute to the promotion of STAT3 as a new therapeutic target.
Cardiac tissue loss is one of the most important factors leading to the unsatisfactory recovery even after treatment of ischemic heart disease. Melatonin, a circadian molecule with marked antioxidant ...properties, protects against ischemia–reperfusion (IR) injury. In particular, the myocardial protection of melatonin is substantial. We initially focus on the cardioprotective effects of melatonin in myocardial IR. These studies showed how melatonin preserves the microstructure of the cardiomyocyte and reduces myocardial IR injury. Thereafter, downstream signaling pathways of melatonin were summarized including Janus kinase 2/signal transducers and activators of transcription 3, nitric oxide‐synthase, and nuclear factor erythroid 2 related factor 2. Herein, we propose the clinical applications of melatonin in several ischemic heart diseases. Collectively, the information summarized in this review (based on in vitro, animal, and human studies) should serve as a comprehensive reference for the action of melatonin in cardioprotection and hopefully will contribute to the design of future experimental research.
The endoplasmic reticulum (ER) is an important intracellular membranous organelle. Previous studies have demonstrated that the ER is responsible for protein folding and trafficking, lipid synthesis ...and the maintenance of calcium homeostasis. Interestingly, the morphology and structure of the ER were recently found to be important. Melatonin is a hormone that anticipates the daily onset of darkness in mammals, and it is well known that melatonin acts as an antioxidant by scavenging free radicals and increasing the activity of antioxidant enzymes in the body. Notably, the existing evidence demonstrates that melatonin is involved in ER homeostasis, particularly in the morphology of the ER, indicating a potential protective role of melatonin. This review discusses the existing knowledge regarding the implications for the involvement of melatonin in ER homeostasis.
Esophageal squamous carcinoma (ESCC) is a prevalent and highly lethal malignant tumor, with a five-year survival rate of approximately 20 %. Tumor-associated macrophages (TAMs) are the most prominent ...immune cells in the tumor microenvironment (TME), comprising over 50 % of the tumor volume. TAMs can be polarized into two distinct phenotypes, M1-type and M2-type, through interactions with cancer cells. M2-type TAMs are more abundant than M1-type TAMs in the TME, contributing to tumor progression, such as tumor cell survival and the construction of an immunosuppressive environment. This review focuses on the role of TAMs in ESCC, including their polarization, impact on tumor proliferation, angiogenesis, invasion, migration, therapy resistance, and immunosuppression. In addition, we discuss the potential of targeting TAMs for clinical therapy in ESCC. A thorough comprehension of the molecular biology about TAMs is essential for the development of innovative therapeutic strategies to treat ESCC.
Display omitted
•Summary of TAMs polarization in the tumor microenvironment.•A review on the role of TAMs in the progression and metastasis in ESCC.•Contribution of TAMs to treatment resistance and immunosuppressive microenvironment formation in ESCC.•Proposal of the possibility of targeting TAMs for the ESCC therapy.
PDF
