Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.

Cognitive impairment is a decline in people’s ability to think, learn, and remember, and so forth. Cognitive impairment is a global health challenge that affects the quality of life of thousands of people. The condition covers a wide range from mild cognitive impairment to severe dementia, which includes Alzheimer’s disease (AD) and Parkinson’s disease (PD), among others. While the etiology of cognitive impairment is diverse, the role of chemokines is increasingly evident, especially in the presence of chronic inflammation and neuroinflammation. Although inflammatory chemokines have been linked to cognitive impairment, cognitive impairment is usually multifactorial. Researchers are exploring the role of chemokines and other inflammatory mediators in cognitive dysfunction and trying to develop therapeutic strategies to mitigate their effects. The pathogenesis of cognitive disorders is very complex, their underlying causative mechanisms have not been clarified, and their treatment is always one of the challenges in the field of medicine. Therefore, exploring its pathogenesis and treatment has important socioeconomic value. Chemokines are a growing family of structurally and functionally related small (8–10 kDa) proteins, and there is growing evidence that pro-inflammatory chemokines are associated with many neurobiological processes that may be relevant to neurological disorders beyond their classical chemotactic function and play a crucial role in the pathogenesis and progression of cognitive disorders. In this paper, we review the roles and regulatory mechanisms of pro-inflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CCL11, CCL20, and CXCL8) in cognitive impairment. We also discuss the intrinsic relationship between the two, hoping to provide some valuable references for the treatment of cognitive impairment.

Fibrosis could happen in every organ, leading to organic malfunction and even organ failure, which poses a serious threat to global health. Early treatment of fibrosis has been reported to be the turning point, therefore, exploring potential correlates in the pathogenesis of fibrosis and how to reverse fibrosis has become a pressing issue. As a mechanism-sensitive cationic calcium channel, Piezo1 turns on in response to changes in the lipid bilayer of the plasma membrane. Piezo1 exerts multiple biological roles, including inhibition of inflammation, cytoskeletal stabilization, epithelial-mesenchymal transition, stromal stiffness, and immune cell mechanotransduction, interestingly enough. These processes are closely associated with the development of fibrotic diseases. Recent studies have shown that deletion or knockdown of Piezo1 attenuates the onset of fibrosis. Therefore, in this paper we comprehensively describe the biology of this gene, focusing on its potential relevance in pulmonary fibrosis, renal fibrosis, pancreatic fibrosis, and cardiac fibrosis diseases, except for the role of drugs (agonists), increased intracellular calcium and mechanical stress using this gene in alleviating fibrosis.

The occurrence and development of central nervous system (CNS) diseases is a multi-factor and multi-gene pathological process, and their diagnosis and treatment have always posed a serious challenge in the medical field. Therefore, exploring the relevant factors in the pathogenesis of CNS and improving the diagnosis and treatment rates has become an urgent problem. Piezo1 is a recently discovered mechanosensitive ion channel that opens in response to mechanical stimuli. A number of previous studies have shown that the Piezo channel family plays a crucial role in CNS physiology and pathology, especially in diseases related to CNS development and mechanical stimulation. This article comprehensively describes the biological properties of Piezo1, focuses on the potential association between Piezo1 and CNS disorders, and explores the pharmacological roles of Piezo1 agonists and inhibitors in treating CNS disorders.

Many physiological processes in the human body are initiated by mechanical signals, which are transmitted via ion channels. Piezo-type mechanosensitive ion channel component 1 (Piezo1) is a protein highly expressed in the brain, playing a critical role in sensing changes in the mechanical microenvironment. Extensive research has demonstrated that Piezo1 is an essential component for generating currents in mechanically activated cation channels. It is involved in several key processes in the nervous system, including neuronal development and differentiation, nerve regeneration, axon guidance, and myelination. Demyelinating diseases, characterized by the loss of nerve myelin sheaths, occur in the central or peripheral nervous system. These diseases are clinically challenging due to their diverse etiologies, multiple types, poor prognosis, and lack of definitive cures. This article aims to review the current research on the role of Piezo1 in myelination and its involvement in demyelinating diseases, as well as to explore the potential of targeting Piezo1 for therapeutic interventions in such conditions.

Direct or indirect damage to the nervous system (such as inflammation or tumor invasion) can lead to dysfunction and pain. The generation of pain is mainly reflected in the activation of glial cells and the abnormal discharge of sensory neurons, which transmit stronger sensory information to the center. P2Y12 receptor plays important roles in physiological and pathophysiological processes including inflammation and pain. P2Y12 receptor involved in the occurrence of pain as a sensory information mediator, which enhances the activation of microglia and the synaptic plasticity of primary sensory neurons, and reaches the higher center through the ascending conduction pathway (mainly spinothalamic tract) to produce pain. While the application of P2Y12 receptor antagonists (PBS-0739, AR-C69931MX and MRS2359) have better antagonistic activity and produce analgesic pharmacological properties. Therefore, in this article, we discussed the role of the P2Y12 receptor in different chronic pains and its use as a pharmacological target for pain relief.