Acupuncture, a therapeutic practice rooted in traditional Chinese medicine and integrated with modern neuroscience, achieves its effects by stimulating sensory nerves at specific anatomical points known as acupoints. This review systematically explores the therapeutic components of acupuncture, emphasizing the interplay between sensory nerve characteristics and neural signaling pathways. Key factors such as acupoint location, needling depth, stimulation intensity, retention time, and the induction of sensations (e.g., Deqi) are analyzed for their roles in neural activation and clinical outcomes. The review highlights how variations in spinal segment targeting, tissue-specific receptor activation, and stimulation modalities (e.g., manual acupuncture, electroacupuncture, moxibustion) influence therapeutic effects. Emerging evidence underscores the significance of ion channels, dermatomes, myotomes, and gene-specific pathways in mediating systemic effects. Additionally, the differential roles of mechanical, thermal and nociceptive stimuli and the temporal dynamics of sensory and immune responses are addressed. While insights from animal models have advanced our understanding, their translation to clinical practice requires further investigation. This comprehensive review identifies critical parameters for optimizing acupuncture therapy, advocating for individualized treatment strategies informed by neuroanatomical and neurophysiological principles, ultimately enhancing its precision and efficacy in modern medicine. Please cite this article as: Wie HS, Kim SN. Therapeutic components of acupuncture stimulation based on characteristics of sensory nerve and nervous signaling pathway. J Integr Med. 2025; 23(2): 106-112.
Humans ; Acupuncture Therapy/methods* ; Signal Transduction ; Animals ; Sensory Receptor Cells/physiology* ; Acupuncture Points

OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

Sucrose non-fermenting 1-related protein kinase 1 (SnRK1) is one of the highly conserved Ca²⁺ non-dependent serine/threonine protein kinases, playing a crucial role in regulating the stress responses, growth, and development of plants. SnRK1 is a three-subunit complex, and it is involved in responding to the signaling transduction induced by low-energy/low-sugar conditions. SnRK1 responds biotic and abiotic stress conditions (such as salt, drought, low/high temperatures, and diseases) through phosphorylation of key metabolic enzymes and regulatory proteins, regulation of transcription, and interactions with other proteins. Furthermore, SnRK1 is not only involved in hormone signaling pathways mediated by abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA), but also regulates plant autophagy by inhibiting the activity of target of rapamycin (TOR). In this review, we summarized the current results of research on the discovery, structure, and classification of plant SnRK1 and its roles in the stress responses, growth, and development of plants. Furthermore, this article proposes the directions of future research. This review provides good genetic resources and a theoretical basis for the genetic improvement and biological breeding for enhancing the stress tolerance of crops.
Stress, Physiological/physiology* ; Protein Serine-Threonine Kinases/metabolism* ; Plant Development/genetics* ; Signal Transduction ; Gene Expression Regulation, Plant ; Plant Proteins/physiology* ; Plants/metabolism* ; Arabidopsis Proteins/physiology* ; Plant Growth Regulators/metabolism*

Calcineurin B-like protein (CBL)-interacting protein kinases (CIPKs) are a group of Ser/Thr protein kinases, playing a crucial role in the growth, development, and stress responses of plants. CIPKs can undergo autophosphorylation or target the phosphorylation of other signaling factors in responses to biotic and abiotic stresses. In addition, they are involved in the signaling pathways of plant hormones such as abscisic acid (ABA), gibberellic acid (GA), ethylene (ETH), and salicylic acid (SA) to regulate plant growth and development. Furthermore, CIPKs respond to stresses such as salinity, drought, cold, and heavy metals by forming complexes through specific interactions with CBLs. In this study, we summarized the discovery, structures, classification, regulatory mechanisms, and roles of CIPKs in plant responses to stresses and made an outlook on the future research directions. This review is expected to provide genetic resources and theoretical foundations for the genetic improvement and breeding of crops with stress tolerance.
Stress, Physiological/physiology* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/physiology* ; Plant Growth Regulators/metabolism* ; Plant Proteins/genetics* ; Plants/metabolism*

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans ; Virus Replication/genetics* ; Signal Transduction ; Membrane Proteins/metabolism* ; A549 Cells ; Vesiculovirus/physiology* ; Interferon-beta/metabolism* ; Interferon Regulatory Factor-3/genetics* ; Interferon Type I/metabolism* ; Vesicular Stomatitis/immunology* ; Gene Knockdown Techniques ; Vesicular stomatitis Indiana virus/physiology* ; RNA, Small Interfering/genetics*

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

Leukocyte-specific protein 1 (LSP1) is an F-actin binding protein expressed in various leukocytes, including lymphocytes, mononuclear macrophages, and neutrophils. LSP1 is highly conserved across different species. Human LSP1 protein contains 339 amino acids, featuring a Ca²⁺ binding site in the acidic NH2-terminal region and multiple F-actin binding domains along with phosphorylatable sites in the basic COOH-terminal region. Under Ca²⁺ regulation, the COOH-terminal domain of LSP1 binds to F-actin to regulate cell movement and signal transduction. Additionally, LSP1 activates the mitogen-activated protein kinase (MAPK) signaling pathway through phosphorylation mediated by protein kinase C (PKC) and MAPK-activated protein kinase-2, thereby regulating leukocyte proliferation and chemotaxis. The main effects of LSP1 on leukocytes are as follows: LSP1 plays important roles in neutrophil and macrophage migration, affecting cell adhesion, polarization and movement. LSP1 also functions in endothelial cells to regulate leukocyte transendothelial migration. In addition, LSP1 regulates macrophage phagocytosis through interaction with myosin 1e. Moreover, LSP1 regulates leukocyte proliferation and differentiation and plays significant roles in the development of leukemia and other tumors. In summary, LSP1 regulates leukocyte morphology, movement and function through interactions with cytoskeletal and signaling proteins. This review provides a comprehensive summary of these aspects.
Humans ; Leukocytes/cytology* ; Animals ; Cytoskeleton/metabolism* ; Microfilament Proteins/physiology* ; Cell Movement ; Signal Transduction

Objective To investigate the role and mechanism of the zinc finger protein Kruppel-like transcription factor 9 (KLF9) in the stimulation of type I interferon expression induced by herpes simplex virus type 1 (HSV-1) in macrophages. Methods Agarose Gel electrophoresis, quantitative real-time PCR (qRT-PCR) and western blot analyses were employed to detect the KLF9 relative expression in bone marrow-derived macrophages (BMDMs) from Klf9^-/- (gKO) mice and wild-type (WT) mice. RNA-seq analysis was utilized to identify the potential targeted genes upon HSV-1 stimulation in BMDMs. ELISA was used to measure the potent of IFN-β in the supernatant of BMDMs derived from gKO and WT mice after HSV-1 stimulation. qRT-PCR analysis was employed to further confirm the changes of Ifnb1 and interferon-stimulated gene (ISG) such as interferon-induced protein with tetratricopeptide repeats 1 (Ifit1), interferon-stimulated exonuclease gene 20 (Isg20), cholesterol 25-hydroxylase (Ch25h) and 2'-5' oligoadenylate synthetase-like 1 (Oasl1). Western blot was used to detect the expression of phosphorylated interferon regulatory factor-3 (p-IRF3), IRF3, phosphorylated interferon regulatory factor-7 (p-IRF7), IRF7, phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) and NF-κB p65. CUT-Tag and ChIP-qPCR assay were utilized to confirm the binding region of KLF9 in Ifnb1. Results The KLF9 expression was significantly decreased in BMDMs from gKO mice compared with that from WT mice. The RNA-seq analysis showed that Klf9 deletion in BMDMs resulted in an impaired type I interferon signaling pathway. The qRT-PCR analysis revealed that Klf9 deletion in BMDMs led to a significant decrease of Ifnb1 and ISG such as Ifit1, Ch25h and Oasl1 except Isg20. Moreover, ELISA revealed that Klf9 knockout in BMDMs resulted in a significant decrease of IFN-β secreted from BMDMs. Mechanistically, KLF9 directly binds to the promoter of Ifnb1. Conclusion KLF9 is essential for macrophages to resist HSV-1 infection.
Animals ; Kruppel-Like Transcription Factors/physiology* ; Interferon-beta/metabolism* ; Macrophages/virology* ; Mice ; Herpesvirus 1, Human/physiology* ; Mice, Knockout ; Signal Transduction ; Mice, Inbred C57BL ; Interferon Regulatory Factor-3/genetics* ; Interferon Regulatory Factor-7/genetics* ; Gene Expression Regulation

Infertility has become one of the most serious diseases worldwide, and 50% of this disease can be attributed to male-related factors. Spermatogenesis, by definition, is a complex process by which spermatogonial stem cells (SSCs) self-renew to maintain stem cell population within the testes and differentiate into mature spermatids. It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility. Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs. In this review, we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal, differentiation, and apoptosis of SSCs, and we illustrate the networks of genes and signaling pathways in SSC fate determinations. We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways. This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.
Humans ; Male ; Signal Transduction/physiology* ; Apoptosis/physiology* ; Spermatogenesis/physiology* ; Cell Differentiation ; Adult Germline Stem Cells/physiology* ; Spermatogonia/cytology* ; Gene Expression Regulation ; Animals ; Infertility, Male/genetics* ; Cell Self Renewal/genetics*