Cell Signaling

Review Article Open Access

PDE4 inhibition and enhancement of human memory and cognition

Graeme B. Bolger

Two distinct, but intertwining, threads of inquiry have demonstrated that the PDE4, or cAMP-selective, phosphodiesterases, have an essential role in human cognition, learning and memory. Study of genetically-modified preclinical models, and of humans with mutations in the PDE4D gene, has provided some of the most rigorous proof of the importance of PDE4 signaling in the CNS. More recently, clinical trials of PDE4-selective inhibitors have shown promising clinical activity in disorders of cognition and memory.

Research Article Open Access

The extract of Nicotiana glauca induces apoptosis in rhabdomyosarcoma cells

Lucía Pronsato , Lorena Milanesi , Andrea Vasconsuelo , Natalia Frattini , Nicolás Blanco

Cancer is a leading cause of childhood mortality, with rhabdomyosarcoma (RMS) being the most prevalent type diagnosed in approximately two-thirds of pediatric cancer cases, particularly the embryonal subtype. RMS represents the most common soft tissue sarcoma in children and adolescents, accounting for around 2-3.5% of all pediatric malignancies [1].

Commentary Open Access

Cognitive impairment in hemodialysis needs sufficient attention

Jun Liu , Yani He , Kehong Chen

Hemodialysis is the most common form of kidney replacement worldwide. It is expected that the acceptance rate of hemodialysis will continue to increase in the coming decades [1]. About 89% of dialysis patients worldwide receive hemodialysis. The majority of these patients are living in high-income countries or middle to high-income countries such as Brazil and South Africa.

Commentary Open Access

Recombinant protein synthesis and isolation of human interferon alpha-2 in cyanobacteria

Anastasios Melis , Bharat Kumar Majhi

Interferons (IFNs) are a class of small immunological proteins that are secreted by infected cells during viral or bacterial infections to combat and prevent infection propagation [1]. They play important roles in triggering signal cascade processes inside the cell that activate other immune cells and limit viral multiplication.

Commentary Open Access

Insights into early acne pathogenesis: Exploring intercellular dynamics and key dysregulated genes

Min Deng , Kiana Farahani , George W. Agak

Acne vulgaris, the most common skin condition worldwide, affects over 85% of adolescents, with nearly half continuing to experience it into adulthood. The Scarring and post-inflammatory hyperpigmentation associated with acne can profoundly impact mental health and self-esteem, underscoring the importance of early and effective treatment [1].

Commentary Open Access

Comment on “Hsa_Circ_0105596/FTO inhibits progression of Parkinson’s disease by sponging miR-187-3p and regulating eEF2”

Taoli Liu , Shumin Cheng , Qingqing Zhu

Parkinson’s disease (PD), a progressive neurodegenerative disorder, characterized by clinical features such as bradykinesia and resting tremor. It is characterized by specific neuropathological changes. These changes include the degeneration of dopaminergic neurons in the substantia nigra (SN) pars compacta.

Commentary Open Access

The role of stress granules in heavy metal-induced carcinogenesis

Rukayat Aromokeye , Megan Carver , Haining Zhu , Lei Wang

Stress granules (SGs) are dynamic, membraneless organelles that assemble in response to cellular stress, such as oxidative stress, hypoxia, or nutrient deprivation [1,2]. Protein translation typically is halted under stress conditions, leading to assembly of SGs containing mRNAs, RNA-binding proteins (RBPs), and other proteins.

Commentary Open Access

The role of circulating anti-aging αKlotho in cardiac aging

Dong I Lee , Dao-Fu Dai

Aging is an inevitable biological process that significantly affects various organs, including the heart. Cardiac aging, with its associated structural and functional changes, can lead to left ventricular (LV) hypertrophy, diastolic dysfunction, increased arterial stiffness, and reduced overall cardiac functional reserve [1,2].

Commentary Open Access

The combination of TSPO ligands and CDK1 inhibitors may be a novel approach for the treatment of malignant peripheral nerve sheath tumor

Xingnan Zhang , Song Liu

MPNSTs are aggressive Schwann cell-derived sarcomas, frequently associated with NF1 mutations. Traditional treatments, including surgery and chemotherapy, are largely ineffective, highlighting the urgent need for novel therapeutic strategies. NF1 loss leads to RAS pathway activation, which in turn activates multiple signaling cascades, including RAF-MEK-ERK1/2, PI3K-AKT, and RalGDS pathways. Inhibition of these pathways has been explored, with MEK inhibitors, such as selumetinib, showing some promise in clinical trials (NCT03433183).

Commentary Open Access

Sirt1-mediated deacetylation in MAFLD: Mechanisms and therapeutic implications

Libang Chen , Qian Lu , Tingting Yang

Apart from alcohol and other definitive factors, metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a clinicalpathological syndrome characterized by hepatic steatosis and lipid accumulation.

Commentary Open Access

A new role of dopamine receptor D2 agonist ropinirole: Targeting NAT10 for treating periodontitis

Jiahui Tan , Jialei Wu , Lufei Wang

Periodontitis is a chronic inflammatory disease that affects more than 40% of the adult population aged over 30 years in the United States, indicating a high prevalence [1]. It impairs the integrity of the tooth-supporting tissue with clinical manifestations featured of gingiva bleeding, periodontal ligament degradation, and alveolar bone resorption. Periodontitis is a multifactorial disease, involving interactions of bacterial pathogens, host immune responses and environmental factors such as smoking [2].

Commentary Open Access

Complex actions of amyloid beta on hippocampal neurogenesis in Alzheimer’s disease pathogenesis

Jaehoon Song , Inhee Mook-Jung

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. One of the key pathological hallmarks of AD is the accumulation of amyloid beta (Aβ), a peptide derived from the sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases .

Commentary Open Access

Engineered Ag135Cu60 nanoclusters with buckminsterfullerene topology: Structure and optical dynamics

QiKai Han , Li Tang , Shuxin Wang

Metal nanoclusters, serving as a mesoscopic bridge between discrete atoms and bulk materials, have emerged as a frontier in the convergence of coordination chemistry and material science.

Commentary Open Access

Regulating ferroptosis by glutathione s-transferases: From mechanistic to potential therapeutic targets

Yanyun Shi , Qi Yao

Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation. In recent years, certain isoforms of glutathione-S-transferases (GSTs) have been identified that may play a key role in regulating ferroptosis. Previous study demonstrated that the NRF2/GSH/GST/RLIP76 and MRP1 axis acts as an independent anti-ferroptosis pathway. Furthermore, this study evaluated the therapeutic potential of mifepristone (RU486) for mitigating acetaminophen (APAP)-induced liver injury in vivo.

Commentary Open Access

Beyond single targets: Crosstalk between endoplasmic reticulum stress, ferroptosis, and vitamin D signaling in stroke treatment

Yifeng Zhang , Xiaolu Wang , Zimeng Chen , Yanqiang Wang

Stroke remains a leading cause of death and long-term disability worldwide, with ischemic stroke representing approximately 85% of all stroke cases. Cerebral ischemia-reperfusion (I/R) injury significantly exacerbates neuronal damage through mechanisms such as oxidative stress, ferroptosis, and endoplasmic reticulum stress (ERS).

Commentary Open Access

Revisiting the effects of curcumin on postmenopausal women’s health—insights from a systematic review and meta-analysis

Dachuan Jin , Shunqin Jin

The myriad health issues triggered by hormonal changes in postmenopausal women have garnered increasing attention in recent years. Among various nutraceuticals and phytoestrogens, curcumin—a bioactive compound derived from Curcuma longa—has emerged as a promising candidate due to its favorable safety profile, multi-targeted biological activities, and growing evidence supporting its antioxidant, anti-inflammatory, and metabolic benefits.

Commentary Open Access

Gut microbiota-immunity interaction and personalized immune response

Chien Dinh Huynh

As presented in our previous article, the human immune system is built upon a genetic framework passed down through countless generations. Traditional dietary habits rooted in specific ethnicities have fostered profound immune diversity, enabling adaptation to harsh environmental conditions and ultimately ensuring survival. Consequently, it’s evident that each individual’s immune characteristics are uniquely shaped by a combination of racial background, environmental exposure, and dietary practices.

Commentary Open Access

NCAM1: A newly discovered immune checkpoint in molluscs and its functions in immune regulation

Muchun He , Renle Chang , Jiejie Sun , Linsheng Song

Natural killer cells (NK cells), a unique subset of cytotoxic lymphocytes, play pivotal roles in immune defense through directly recognizing and eliminating pathogen-infected cells or cancer cells. Currently, NK cells have been identified in humans, mice, and teleost fishes. However, the existence, identification and functional characterization of NK-like cells in invertebrates remain poorly understood. Studies in Drosophila [6] and shrimp [7] had revealed that their undefined type of hemocytes analogous to vertebrate NK cells had direct cytotoxic activity against invading pathogens or abnormal cells. 

Commentary Open Access

Hepatic stellate cells as RSPO3-Wnt/β- catenin hubs governing liver zonation and regenerative capacity

Qiang Yang , Chunsheng Lin , Ying Cai , Chao Wang , Zhibo Wang , Sifan Guo , Shi Qiu , Aihua Zhang

The liver emerges as an ultimate metabolic nexus—a polyfunctional organ that simultaneously performs biochemical detoxification, macromolecular processing, and systemic nutrient governance. While hepatic stellate cells (HSCs) were historically confined to their fibrogenic identity, their broader homeostatic orchestration remained enigmatic. RSPO3 as a linchpin in hepatocyte dynamics, with targeted pharmacological modulation enhancing hepatic lobular repatterning, regenerative capacity, and metabolic optimization.

Commentary Open Access

From mitosis to mutagenesis: Chromosomal passenger proteins at the crossroads of replication stress and cancer resilience

Shirley K. Knauer , Roland H. Stauber

The chromosomal passenger complex (CPC), comprising Survivin, Aurora B kinase, INCENP, and Borealin, is classically known for its essential functions during mitosis. However, recent findings expand the CPC's role beyond cell division, uncovering novel functions in replication stress response and genome stability maintenance.

Commentary Open Access

Confine to create: ER-endosome contacts foster autophagy initiation

Juliane Da Graça , Etienne Morel

Autophagy is a conserved cellular process in which eukaryotic cells degrade and recycle intracellular material via a dedicated trafficking toward lysosomes. Under starvation, autophagy is initiated by the formation of a double-membrane organelle called the autophagosome, which originates from the closure and maturation of a transient membrane structure known as the phagophore. The precise membrane source of the phagophore and the mechanisms underlying its biogenesis remain incompletely understood.

Commentary Open Access

Chemokine-like Orion presentation as a potential switch in phagocytic signaling pathway activation during neuronal remodeling

Charline Gal , Clarisse Perron , Jean-Maurice Dura , Ana Boulanger

Immature nervous systems are initially overpopulated with neurons. A crucial step of remodeling that removes inappropriate connections is required and performed predominantly by phagocytic glial cells. The Drosophila chemokine-like Orion tags axons to be eliminated. Could the way Orion is presented by neurons be the critical factor in modulating subsequent intracellular glial responses?

Commentary Open Access

Targeting inflammation in progeria – insights from combined baricitinib and lonafarnib treatment in a mouse model of progeria

Moritz Schroll , Karima Djabali

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare and fatal premature aging disorder caused by progerin accumulation, leading to nuclear abnormalities, systemic inflammation, and early cardiovascular decline. Lonafarnib, a farnesyltransferase inhibitor (FTI), improves nuclear shape and extends lifespan, but its efficacy is limited and accompanied by pro-inflammatory effects. Here, we discuss preclinical findings from a combination therapy using the JAK1/2 inhibitor baricitinib (BAR) with FTI in a progeria mouse model. 

Commentary Open Access

Angiotensin-(1-7) steers macrophages to inflammation resolution

Simone de Araújo , Erick Bryan de Sousa Lima , Lirlândia P. Sousa , Mauro Martins Teixeira

Angiotensin-(1-7) [Ang-(1-7)] is a biologically active peptide of the renin–angiotensin system (RAS) that counterbalances the actions of angiotensin II (Ang II), primarily through binding to the Mas receptor (MasR). This axis exerts significant immunomodulatory effects by influencing several features of leukocytes, including macrophage function, a central component in the resolution of inflammation. Macrophages contribute to tissue homeostasis by clearing apoptotic cells, releasing anti-inflammatory mediators and supporting tissue repair.

Commentary Open Access

Neuroimmune interplay in peripheral neuropathies

Xiangyun Yao , Cunyi Fan , Song Guo Zheng

The interplay between neural cells and immune cells is a determinant factor for microenvironment restoration following nerve injury. Nerve-resident immune cells respond microenvironment signals and switch to pro-inflammatory or pro-regenerative phenotype. These phenotypes have different effects on axon regeneration. Early-phase neuroinflammation clears debris and remodels a permissive microenvironment for nerve repair. However, persistent and overactive inflammation is destructive and detrimental to regeneration. Despite all this information, our understanding of neuroimmune interplay in traumatic and diabetic neuropathies remains poor.

Commentary Open Access

Insights into the methyltransferase activity and methylation status of PRDM16 in malignant tumors

Yu Wang , Yuting Wang , Anjia Han

The PRDM16 (PRDI-BF1-interacting and RIZ1-homologous domain 16) participates in a range of biological processes including tumorigenesis. The protein regulates gene transcription through intrinsic chromatin-modifying enzymatic activity or by forming complexes with histone modifications or other nuclear proteins. Accumulating evidence indicates that the methyltransferase activity and its methylation status of PRDM16 had been further studied.

Commentary Open Access

Dual roles, targeting dilemmas, and future priorities: Rethinking METTL-mediated m6A modification in head and neck cancer

Ming Yang , Han Zhu , Zile Zhang , Xuexia Liu , Hua Zhang , Gang Qin

With the recently published review in Cellular Signaling, we highlight the importance of Methyltransferase-like (METTL) family-mediated N6-methyladenosine (m6A) modification in head and neck cancer (HNC) progression, providing a theoretical foundation for their potential use as therapeutic targets.

Commentary Open Access

Insulin or islet: That’s the question

Byung-Joon Kim , Hee-Kyeong Park , Jun-Seop Shin , Jin Kuk Kim , Kwang-Won Kim

This commentary discusses our recent findings that, contrary to the β-cell rest hypothesis, early short-term insulin administration in a mouse model of marginal β-cell deficiency paradoxically worsened glycemic control and induced adverse α-cell-mediated islet remodeling. Early insulin intervention is hypothesized to preserve β-cell function; however, its utility in marginal β-cell deficiency is not well-established.