Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation. It can activate janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway. As one of the important signal transduction pathways in cells, JAK2/STAT3 signaling pathway plays a critical role in cell proliferation and differentiation by affecting the activation state of downstream effector molecules. The activation of JAK2/STAT3 signaling pathway is involved in tumorigenesis and development. It contributes to the formation of tumor inflammatory microenvironment and is closely related to the occurrence and development of many human tumors. This article focuses on the relationship between IL-6/JAK2/STAT3 signaling pathway and liver cancer, breast cancer, colorectal cancer, gastric cancer, lung cancer, pancreatic cancer and ovarian cancer, hoping to provide references for the research of cancer treatment targeting key molecules in IL-6/JAK2/STAT3 signaling pathway.

Programmed cell death is an active extinction process, including autophagy, ferroptosis, pyroptosis, apoptosis, and necroptosis. m⁶A is a reversible RNA modification which undergoes methylation under the action of methylases (writers), and is demethylated under the action of demethylases (erasers). The RNA base site at which m⁶A is modified is recognized by specialized enzymes (readers) which regulate downstream RNA translation, decay, and stability. m⁶A affects many aspects of mRNA metabolism, and also plays an important role in promoting the maturation of miRNA, the translation and degradation of circRNA, and the stability of lncRNA. The regulatory factors including writers, erasers and readers promote or inhibit programmed cell death via up-regulating or down-regulating downstream targets in a m⁶A-dependent manner to participate in the process of disease. In this review, we summarize the functions of m⁶A with particular reference to its role in programmed cell death.

Calpains are a family of Ca²⁺‑dependent cysteine proteases that participate in various cellular processes. Calpain 3 (CAPN3) is a classical calpain with unique N‑terminus and insertion sequence 1 and 2 domains that confer characteristics such as rapid autolysis, Ca²⁺‑independent activation and Na⁺ activation of the protease. CAPN3 is the only muscle‑specific calpain that has important roles in the promotion of calcium release from skeletal muscle fibers, calcium uptake of sarcoplasmic reticulum, muscle formation and muscle remodeling. Studies have indicated that recessive mutations in CAPN3 cause limb‑girdle muscular dystrophy (MD) type 2A and other types of MD; eosinophilic myositis, melanoma and epilepsy are also closely related to CAPN3. In the present review, the characteristics of CAPN3, its biological functions and roles in the pathogenesis of a number of disorders are discussed.

Major facilitator superfamily (MFS) is the maximum and most diversified membrane transporter, acting as uniporters, symporters and antiporters. MFS is considered to have a good development potential in the transport of drugs for the treatment of brain diseases. The major facilitator superfamily domain containing protein 2a (Mfsd2a) is a member of MFS. Mfsd2a-knockout mice have shown a marked decrease of docosahexaenoic acid (DHA) level in brain, exhibiting neuron loss, microcephaly and cognitive deficits, as DHA acts essentially in brain growth and integrity. Mfsd2a has attracted more and more attention in the study of nervous system diseases because of its critical role in maintaining the integrity of the blood-brain barrier (BBB) and transporting DHA, including inhibiting cell transport in central nervous system endothelial cells, alleviating BBB injury, avoiding BBB injury in cerebral hemorrhage model, acting as a carrier etc. Up to now, the clinical research of Mfsd2a in nervous system diseases is rare. This article reviewed the current research progress of Mfsd2a in nervous system diseases. It summarized the physiological functions of Mfsd2a in the occurrence and development of intracranial hemorrhage (ICH), Alzheimer’s disease (AD), sepsis-associated encephalopathy (SAE), autosomal recessive primary microcephaly (MCPH) and intracranial tumor, aiming to provide ideas for the basic research and clinical application of Mfsd2a.

Lysophosphatidic acid receptor 1(Lpar1), which is found in almost all human tissues but is most abundant in the brain, can couple to G protein-coupled receptors (GPCRs) and participate in regulating cell proliferation, migration, survival, and apoptosis. Endothelial differentiation gene-2 receptor (Edg2), the protein encoded by theLpar1gene, is present on various cell types in the central nervous system (CNS), such as neural stem cells (NSCs), oligodendrocytes, neurons, astrocytes, and microglia.Lpar1deletion causes neurodevelopmental disorders and CNS diseases, such as brain cancer, neuropsychiatric disorders, demyelination diseases, and neuropathic pain. Here, we summarize the possible roles and mechanisms ofLpar1/Edg2 in CNS disorders and diseases and propose thatLpar1/Edg2 might be a potential therapeutic target for CNS disorders and diseases.