Cell Signaling

Commentary Open Access

Unlocking the significance of CD226 in cancer

Weili Sun

CD226 is a transmembrane glycoprotein with a well-defined structural organization, which is primarily expressed on natural killer (NK) cells, cytotoxic T cells, and some subsets of B cells [1,2]. Its primary structure consists of an extracellular domain, a transmembrane domain, and a cytoplasmic tail [1]. Each of these domains contributes to the protein's overall function.

Research Article Open Access

EGCG modulates nuclear formaldehyde-induced Tau phosphorylation in neuronal cells

Shweta Kishor Sonawane, Anshu Raina, Amitabha Majumdar, Madhura Chandrashekar, Subashchandrabose Chinnathambi

Tau pathology in Alzheimer’s disease is known to hamper several cellular functions including  microtubule dynamics, proteostasis etc. Tau is a microtubule-stabilizing protein, playing an important role in maintaining the integrity of the axonal microtubules [1,2].

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.

Commentary Open Access

Friend or foe? The elusive role of ANGPTL4 in inflammation

Yueqi Zhang, MD, Yueqi Zhang, MD, Lei Dai, MD

Angiopoietin-like 4 (ANGPTL4) is a multifaceted secreted protein discovered by three different institutions in 2000 simultaneously [1]. It is expressed in adipose tissues, liver, muscle, heart, kidney, skin, and other tissues. The nutritional, metabolic, and inflammatory status of the organism regulate the expression of ANGPTL4 [2-4].

Review Article Open Access

Review of spinal dural arteriovenous fistulas: Challenges, diagnostics, management, and pathophysiology

Michael Goutnik, Ramya Reddy, Sandra Yan, Brandon Lucke-Wold

Spinal dural arteriovenous fistulae (sdAVFs) are rare (5-10 per million per year), often misdiagnosed vascular lesions most commonly found in the thoracolumbar spine [1-7]. These lesions commonly present with progressive myelopathy in male (approximately 80%) patients who are usually in their 7th decade of life [3-6,8]. 

Commentary Open Access

Commentary: Interferons in Influenza and Streptococcus Pneumoniae co-pathogenesis

Sunil Palani, Keer Sun

Influenza A virus (IAV) and Streptococcus pneumoniae (SPn) are two major respiratory pathogens in humans. IAV infection alone is often self-limited, and SPn colonization can be found in 5-90% of healthy individuals, as normal flora [1,2].

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].

Review Article Open Access

Perspective study of UPR signaling molecules as potential biomarkers in bone metabolism

Yiming Pan, Kaiwen Liu, Yuanlan Ye, Mengtian Fan, Xiaoli Li, Fengjin Guo

The skeletal system consists mostly of extracellular matrix and mineral salts. Osteoblasts and chondrocytes create enormous amounts of extracellular matrix proteins for skeletal systems to grow and sustain. Many skeletal metabolism related proteins are produced by endoplasmic reticulum (ER) and secrete outside cell membrane then form to extracellular oligometric matrix proteins and collagens. 

Commentary Open Access

Biomarkers for monoclonal antibody targeting EGFR in NSCLC: Challenges, current status, and future perspectives

May-Lucie Meyer, Fred R. Hirsch

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths [1]. However, significant improvements in the past decades have been achieved with improved outcomes [2-4]. Several mutations have been described as promoters of oncogenesis, and specific treatments are available, including those for Epidermal Growth Factor (EGFR) mutations [4].

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.

Editorial Open Access

Selecting ideal combined immunotherapy for treating HCC

Rui Han, Lingeng Lu

The discovery of proper sensitizers for immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) treatment represents a significant breakthrough in the field of cancer therapy, but it is still in initial stage [1,2].

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.

Research Article Open Access

Molecular docking combined with in vitro validation study to explore the effect of lupenone on alleviating renal fibrosis based on TGF-?/Smad/CTGF signaling pathway

Xiangpei Wang, Hongyun Liu, Xiaofen Li, Mei Zhang, Feng Xu, Mei Liu, Hongmei Wu

According to the global epidemiological report on chronic kidney disease (CKD) published by The Lancet, CKD is recognized as a global public health problem with high morbidity and mortality [1]. Diabetic nephropathy (DN) is the most main microvascular complication of diabetes and is one of the leading causes of end-stage renal disease (ESRD) and CKD [2].

Editorial Open Access

Radiation induced molecular signalling in the cells: A real struggle between death or breathe

Raj Kumar

Radiation is omnipresent in the universe. Since the primitive period, chemical evolution led to a biological evolution somehow driven by the ionizing and non-ionizing radiation on the Earth’s atmosphere [1,2].

Review Article Open Access

Approach to testicular adrenal rest tumors in children and adolescents with congenital adrenal hyperplasia

Sirmen Kizilcan Cetin, Zehra Aycan

Congenital adrenal hyperplasia (CAH) is a disorder affecting cortisol biosynthesis in the adrenal cortex [1]. 21-hydroxylase deficiency is the most frequent reason for CAH, with an incidence between 1:10.000 and 1:20.000 [2]. Due to the lack of enzyme function, patients with any enzyme deficiency cannot synthesize cortisol effectively. 

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

Aiming for the brain: a new thermogel-based drug delivery platform

Mario Chiariello, Lisa Gherardini

The design of safe drug delivery systems that locally allow efficacious concentration of curative molecules has become the latest frontier in nanomedicine. It usually relies on the entrapment of drugs into micro/nano carriers guaranteeing for the controlled release of the drugs while protecting them from degradation and fast clearance.

Research Article Open Access

Methylphenidate (Ritalin) affects serotoninsignaling differently in young compared to adults. Concomitant behavioral and neuronal recording from dorsal raphe in freely behaving rats

Elizondo GM, Raymond A, Perez-Vasquez C, Dafny N

Attention deficit hyperactivity disorder (ADHD) is a complex behavioral disorder characterized by hyperactivity, increased impulsivity, and inattention [1-3]. Methylphenidate (MPD) is the most
commonly prescribed psychostimulant for management and treatment of ADHD [3-7].

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

Do arrestin oligomers have specific functions?

Vsevolod V. Gurevich

Arrestins were discovered as key players in the conserved two-step homologous desensitization of G protein-coupled receptors (GPCRs): they specifically bind active phosphorylated GPCRs, precluding their coupling to cognate G proteins, thereby stopping (“arresting”) G protein-mediated receptor signaling [1]. 

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

Immune-enhanced nanocomposites provide hope for drug-resistant infection treatment

Tao Zhang, Mo Chen, Sagit Makhanov, XianZuo Zhang, Yao Luo, Chen Zhu

Antibiotic misuse contributes to the emergence of multidrug-resistant organisms, resulting in infections that cause over one million deaths annually [1-3]. Therefore, there is an urgent need to develop new antimicrobial methods. Traditional antibiotic therapy is often incomplete due to the emergence of drug-resistant strains, leading to relapse. 

Commentary Open Access

Deciphering Notch signaling notch by notch

Lidia Borkiewicz, Adolfo Rivero-Müller

The NOTCH receptors are mechanosensing proteins that require cell-cell contact and physical force for activation. While most receptors have evolved to respond to one or a few unique ligands, the four NOTCH receptors can respond to any of the five Delta/Serrate/Lag-2 (DSL) ligands - Jagged (JAG) 1, 2, and Delta-like (DLL) 1, 3, 4 [1].

Commentary Open Access

Camping in the backyard: Identifying extracellular matrix targeting ligands using yeast surface display

Benjamin J Umlauf

Camping trips are often a lot of work, especially with children. Purchasing supplies, finding a location, and dealing with scary animals are often just too much. Inspired by so many films, my family instead set up a tent to camp in the backyard.

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

A vicious cycle happened in the progress of hyperhomocysteinemia, the same may exist in the development of cancer

Chenghua Luo, Dengyu Ji, Wen Wang

Homocysteine (Hcy) metabolism is at the intersection of two metabolic pathways: remethylation and trans-sulfuration, which abnormality can result in hyperhomocysteinemia (HHcy). In the past few years our team has been working on the molecular mechanism of HHcy development.

Commentary Open Access

An essential role for hepatocyte adenosine kinase in regulating fat metabolism and inflammation

Jiayu Yu, Juan Zheng, Chaodong Wu

Metabolic dysfunction-associated steatotic liver disease (MASLD) is comprised of a spectrum of conditions, which is a progressive form of liver disease ranging from simple steatosis to steatohepatitis. The liver regulates fat metabolic homeostasis through de novo lipogenesis, fatty acid uptake and oxidation, low-density lipoprotein secretion in hepatocytes.

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

Commentary to: Anti–miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response

Gabriel Lopez-Berestein, M.D

The major message of this manuscript is that miR-93-5p is a potential therapeutic target in sepsis through the regulation of both innate and adaptive immunity, with possibly a greater benefit for elderly patients than for young patients.

Commentary Open Access

The value of EGFR in individualized treatment for brain metastases in non-small cell lung cancer

Li Tan, Juan Ren

The epidermal growth factor receptor (EGFR) is a member of the ErbB family. It is involved in biological processes such as cell proliferation, angiogenesis, inhibition of apoptosis, adhesion, metastasis, and is associated with the progression of lung cancer [1-3].

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

HK2 fuels anoikis resistance to accelerate ICC metastasis

Xiaojing Du, Sunkuan Hu

Intrahepatic cholangiocarcinoma (ICC), the second most frequent primary liver tumor, is a highly metastatic malignancy and often leads to disaster outcome in majority of patients, bringing significant challenges in the medical field [1].

Commentary Open Access

Development of an authentic light-activated calcium channel

Wenyu Li, Liuqing Wang, Youjun Wang, Lian He

Optogenetics utilizes the fusion of naturally occurring light-sensing proteins with target proteins to induce conformational changes, oligomerization, or dissociation in response to illumination of light with specific wavelengths.

Commentary Open Access

Are the N-terminal derivatives of IGF-I neuropeptides agents for the treatment of Alzheimer's disease?

Laura M. Frago, Sandra Canelles, Vicente Barrios

Alzheimer´s disease (AD) is a devastating disease caused by the accumulation and interaction of tau-containing neurofibrillary tangles and amyloid beta peptide (Aβ) plaques in the brain [1,2].

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

GABA fluctuations driven by astrocytic Glu-GABA exchange explain synaptic acuity

László Héja, Julianna Kardos

Gliocentric paradigms showcase functional association of neurons with astrocytes, as in tripartite glutamatergic synapses. Astrocytes, activated by Glu:3Na(+) symport apply GABAergic inhibitory feedback on synaptic excitation via GABA efflux by GAT-3 reversal and subsequent GABAA activation (astrocytic Glu/GABA exchange [1-3]).

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

Modulation of mitochondrial gene expression by testosterone in skeletal muscle

Lucía Pronsato, Lorena Milanesi, Andrea Vasconsuelo

Testosterone plays a crucial role in determining the body composition of male mammals, including humans, due to its effects on muscle and fat mass. Age-related declines in serum testosterone levels in men have been linked to loss of skeletal muscle mass and strength, and physical performance [1-4].

Commentary Open Access

Commentary: Role of estrogen receptor β in kidney disease

Wen Su, Rong Cao, Qijun Wan, Hui-yao Lan

Chronic kidney disease (CKD) has become a growing global health challenge, impacting over 800 million individuals worldwide [1]. Numerous evidences have shown that women are more resistant to CKD than men before menopause, however this beneficial effect is diminished in those with post-menopause, highlighting the pivotal role of estrogen in kidney disease [2-5].

Commentary Open Access

In search for molecular mechanisms of Post COVID-19 vascular damage

Sarah Halawa, Yasmine Aguib, Magdi H Yacoub

Since the onset of the COVID-19 pandemic, the world has changed significantly with newchallenges constantly arising (Figure 1) [1]. One of the main challenges is the increased prevalence of a prolonged post-COVID-19 syndrome, widely known as "Post COVID", which is currently regarded as a public health issue worldwide [2].

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

Intracellular signaling mechanism of sweat secretion by PACAP

Michio Yamashita, Junko Shibato, Randeep Rakwal, Naoko Nonaka, Fumiko Takenoya, Seiji Shioda

Sweat, an exocrine fluid secreted (sweat gland tissue of the eccrine and apocrine glands) by skin has an indispensable function for regulating body temperature and skin hydration [1]. The eccrine gland performs 90% of sweat secretion and secretory fluid of eccrine glands consists of 99% water and 1% inorganic substances.

Commentary Open Access

Pathogenic contribute of unaffected cardiac cells in female Fabry cardiomyopathy

Andrea Frustaci, MD, Romina Verardo, PhD, Cristina Chimenti, MD

Cardiac hypertrophy is one of the most common manifestations of Fabry disease (FD) [1] and it can be the only clinical expression, in the so called cardiac variant, as result of specific mutation of
alpha-galactosidase-A gene (GLA), as the N215S one [2].

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

Del(5q) MDS and erythroid maturation

Alfredo Fallorina, Tuoen Liu

Myelodysplastic syndromes (MDS) are acquired neoplastic myeloid proliferations in the bone marrow, where hematopoietic stem cells (HSCs) are impacted. MDS are characterized by clonal proliferation of HSCs, recurrent genetic abnormalities, progressive cytopenia, increased risk of acute myeloid leukemia (AML), and myelodysplasia [1].

Commentary Open Access

Probes for cancer metastasis imaging and therapeutic targeting

Suridh Adhikari, Ali Azhdarinia, Mikhail G. Kolonin

Metastasis of cancer is the process by which the primary tumor spreads from the original site to other parts of the body. Palliative care is the most common treatment option available for patients with metastatic cancer, but most patients eventually succumb to the disease due to the lack of therapeutics that can specifically target disseminated tumors [1].

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).

Review Article Open Access

Inhibitory potential of Nelumbo nucifera Gaertn extract on the PI3K/AKT/mTOR signaling pathway

Rakesh Sahu, Bhaskar Sahu

The lotus or Indian lotus has a rich history of traditional use in various cultures for its medicinal properties [1,2], with the increasing prevalence of diseases such as cancer, diabetes, and inflammatory conditions, there is a growing interest in exploring natural products for their therapeutic potential [3-6].

Mini Review Open Access

Can a mouth wash prevent atherosclerosis and ischemic stroke?

Lizymol P.P

Poor oral health, particularly gum disease, has been linked to an increased risk of atherosclerosis and ischemic stroke. The theory behind this connection is that the bacteria involved in gum disease can enter the bloodstream and contribute to inflammation in the arteries, potentially promoting the development of atherosclerosis.

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

Coloring outside the lines: Exploring the dysbiotic impact of azo dyes on gut health and inflammation

Hanan Salah El-Abhar, Marwa Ali-Tammam, Sara Ahmed Zahran, Amal Emad Ali, Suzan Mohamed Mansour

Beyond mere aesthetics, the vibrant hues of fruits, vegetables, and culinary creations evoke sensory experiences that influence perceptions of flavor, freshness, and even nutritional value. This concept highlighted the pivotal role that color can play in the realm of food, serving as a powerful tool to captivate consumers and entice their taste buds.

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

Accelerating metal nanocluster synthesis: A high-throughput approach with machine learning assistance

Li Tang, Shuxin Wang

Metal nanoclusters, consisting of a few to a few hundreds of metal atoms, have been of great scientific interest due to their potential applications in areas like bio-labeling and catalysis [1-9].

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

Sample multiplexing in CyTOF: Path to optimize single-cell proteomic profiling

Muharrem Muftuoglu, Michael Andreeff

In biomedical research, achieving single-cell resolution in investigation of cellular systems is of paramount importance. Ongoing research efforts to explore and decode the heterogeneity in cellular phenotype, functionality, genomics, epigenetics, and transcriptomics in biological systems have propelled significant technological advancements through innovative breakthroughs [1-3].

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

The interplay of regulatory T cells, endoplasmic reticulum stress, and unfolded protein response activation in post-transplant alloimmune hepatitis and autoimmune hepatitis

Kumar Subramanian, Udeme D. Ekong

The incidence and prevalence of autoimmune hepatitis (AIH) globally is 1.28 per 100,000 population-years (95% CI, 1.01-1.63) and 15.65 per 100,000 population (95% CI, 13.42-18.24), respectively [1]. The incidence and prevalence in children is 0.4 and 3.0 cases per 100,000 children [2], and in adults 17 per 100,000 [3,4].

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

Chemotherapy, immunotherapy, and antiangiogenesis: Emerging trends in the comprehensive treatment of advanced gastric cancer

Yuting Ding, Hao Qian, Yitong Tian, Jiaguang Zhang, Xinyi Zhang, Ling Ma, Taisong Li, Ke Jin, Fengyuan Li, Yongqian Shu, Xiaofeng Chen

Gastric or gastroesophageal junction (GEJ) adenocarcinoma remains a fatal condition worldwide, ranking fifth in prevalence and fourth in mortality globally [1]. The treatment of advanced gastric cancer is currently stratified based on MSI (Microsatellite Instability) status and HER2 status.

Commentary Open Access

FBXOing down V-ATPase: Implications for combating cancer metastasis

Zhenyi Wang, Weiyi Zhou, Xiaodong Chen, Zhe Zhao, Dongping Wei

FBXO9, an evolutionarily conserved member of the F-box protein family, functions as a substrate receptor within the Cullin 1-RING ubiquitin ligase complex (CRL1), also known as the SKP1-Cullin 1-F-box (SCF) complex [1].

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?

Review Article Open Access

Integrating “fast” and “slow” systems therapeutics for physiological renormalization in neurodegenerative disorders

Greg Maguire, George Ayoub

In Goodman and Gilman's, “The Pharmacological Basis of Therapeutics,” we were all taught to search for the one molecule that targets a single pathway, and specifically targets only that one pathway, underlying a disease or condition to optimally develop a therapeutic.

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

Potential biomarkers for MCL1 inhibitor sensitivity

Lei Duan, Carl G. Maki

Myeloid cell leukemia-1 (MCL1) is an anti-apoptotic member of the B-cell lymphoma 2 (BCL- 2) family and plays a key role in cancer cell survival and resistance to therapy [1,2]. MCL1 is often
overexpressed in cancers such as leukemia, lymphoma, and solid tumors, allowing cancer cells to evade apoptosis and resist conventional treatments.

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

Carbon nanostructure: Cutting-edge platforms for advanced genetic transport

Sara Yazdani, Mehrdad Mozaffarian, Gholamreza Pazuki, Naghmeh Hadidi

Gene therapy represents a revolutionary approach to treating a wide range of genetic disorders, cancers, and infectious diseases by directly modifying or correcting defective genes within a patient’s cells. Unlike conventional treatments that focus on managing symptoms, gene therapy targets the underlying molecular causes of diseases, offering the potential for long-lasting or permanent cures.

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

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

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

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

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. 

Review Article Open Access

A review on molecular mechanisms underlying the contribution of Tspan8 and CD151 tumor and host exosomes to tumor progression, hematopoiesis and angiogenesis

Kun Zhao, Zhe Wang, Margot Zöller

Tetraspanins associate with many proteins and are involved in numerous activities like the crosstalk between cells and matrix, tumor progression, angiogenesis, and hematopoiesis.