Targeting lysyl oxidase like 2 attenuates OVA-induced airway remodeling partly via the AKT signaling pathway.

BACKGROUND: Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma. METHODS: The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor. RESULTS: Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-ß1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression. CONCLUSIONS: Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.

Recent advances in targeting histone H3 lysine 36 methyltransferases for cancer therapy.

Histone H3 lysine 36 (H3K36) methylation is a typical epigenetic histone modification that is involved in various biological processes such as DNA transcription, repair and recombination in vivo. Mutations, translocations, and aberrant gene expression associated with H3K36 methyltransferases have been implicated in different malignancies such as acute myeloid leukemia, lung cancer, multiple myeloma, and others. Herein, we provided a comprehensive overview of the latest advances in small molecule inhibitors targeting H3K36 methyltransferases. We analyzed the structures and biological functions of the H3K36 methyltransferases family members. Additionally, we discussed the potential directions for future development of inhibitors targeting H3K36 methyltransferases.

Comparison of groundwater storage changes over losing and gaining aquifers of China using GRACE satellites, modeling and in-situ observations.

Groundwater depletion in intensively exploited aquifers of China has been widely recognized, whereas an overall examination of groundwater storage (GWS) changes over major aquifers remains challenging due to limited data and notable uncertainties. Here, we present a study to explore GWS changes over eighteen major aquifers covering an area of 1,680,000 km2 in China using data obtained from the Gravity Recovery and Climate Experiments (GRACE), global models, and in-situ groundwater level observations. The analysis aims to reveal the discrepancy in annual trends, amplitudes, and phases associated with GWS changes among different aquifers. It is found that GWS changes in the studied aquifers represent a spatial pattern of 'Wet-gets-more, Dry-gets-less'. An overall decreasing trend of -4.65 ± 0.34 km3/yr is observed by GRACE from 2005 to 2016, consisting of a significant (p < 0.05) increase of 47.28 ± 3.48 km3 in 7 aquifers and decrease of 103.56 ± 2.4 km3 (∼2.6 times the full storage capacity of the Three Gorges Reservoir) in 10 aquifers summed over the 12 years. The annual GWS normally reaches a peak in late July with an area-weighted average annual amplitude of 19 mm, showing notable discrepancy in phases and amplitudes between the losing aquifers (12 mm in middle August) in northern China and gaining aquifers (28 mm in early July) mostly in southern China. GRACE estimates are generally comparable, but can be notably different, with the results obtained from model simulations and in-situ observations at aquifer scale, with the area-weighted average correlation coefficients of 0.6 and 0.5, respectively. This study highlights different GWS changes of losing and gaining aquifers in response to coupled impacts of hydrogeology, climate and human interventions, and calls for divergent adaptions in regional groundwater management.

[Research status and prospects of probiotics in functional gastrointestinal disorders in infants and toddlers]. / ç›Šç”ŸèŒåœ¨å©´å¹¼å„¿åŠŸèƒ½æ€§èƒƒè‚ ç— ä¸­çš„ç ”ç©¶çŽ°çŠ¶åŠå±•æœ›.

Functional gastrointestinal disorders (FGIDs) are common digestive system diseases in children, which can severely affect the growth and development of infants and toddlers. Probiotics therapy, as a relatively safe treatment method, have attracted the attention of researchers. However, their effectiveness in treating FGIDs in infants and toddlers is still unclear. This article reviews the mechanisms of probiotics in treating FGIDs in infants and toddlers, explores the reasons for the inconsistency in various research results, and aims to provide assistance for the clinical treatment of FGIDs in infants and toddlers and future research.

PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC.

Application of radiomics in ischemic stroke.

In recent years, radiomics has emerged as a novel research methodology that plays a crucial role in the diagnosis and treatment of ischemic stroke. By integrating multimodal medical imaging techniques such as computed tomography and magnetic resonance imaging, radiomics offers in-depth insights into aspects such as the extent of brain tissue damage and hemodynamics. These data help physicians to accurately assess patient condition, select optimal treatment strategies, and predict recovery trajectories and long-term prognoses, thereby enhancing treatment efficacy and reducing the risk of complications. With the anticipated further advancements in radiomic technology, this methodology has great potential for expanded applications in the early detection, treatment, and prognosis of ischemic stroke. The present narrative review explores the burgeoning field of radiomics and its transformative impact on ischemic stroke.

Disruption in CYLC1 leads to acrosome detachment, sperm head deformity, and male in/subfertility in humans and mice.

The perinuclear theca (PT) is a dense cytoplasmic web encapsulating the sperm nucleus. The physiological roles of PT in sperm biology and the clinical relevance of variants of PT proteins to male infertility are still largely unknown. We reveal that cylicin-1, a major constituent of the PT, is vital for male fertility in both mice and humans. Loss of cylicin-1 in mice leads to a high incidence of malformed sperm heads with acrosome detachment from the nucleus. Cylicin-1 interacts with itself, several other PT proteins, the inner acrosomal membrane (IAM) protein SPACA1, and the nuclear envelope (NE) protein FAM209 to form an 'IAM-cylicins-NE' sandwich structure, anchoring the acrosome to the nucleus. WES (whole exome sequencing) of more than 500 Chinese infertile men with sperm head deformities was performed and a CYLC1 variant was identified in 19 patients. Cylc1-mutant mice carrying this variant also exhibited sperm acrosome/head deformities and reduced fertility, indicating that this CYLC1 variant most likely affects human male reproduction. Furthermore, the outcomes of assisted reproduction were reported for patients harbouring the CYLC1 variant. Our findings demonstrate a critical role of cylicin-1 in the sperm acrosome-nucleus connection and suggest CYLC1 variants as potential risk factors for human male fertility.

Antimicrobial susceptibility and resistome of Actinobacillus pleuropneumoniae in Taiwan: a next-generation sequencing analysis.

Actinobacillus pleuropneumoniae infection causes a high mortality rate in porcine animals. Antimicrobial resistance poses global threats to public health. The current study aimed to determine the antimicrobial susceptibilities and probe the resistome of A. pleuropneumoniae in Taiwan. Herein, 133 isolates were retrospectively collected; upon initial screening, 38 samples were subjected to next-generation sequencing (NGS). Over the period 2017-2022, the lowest frequencies of resistant isolates were found for ceftiofur, cephalexin, cephalothin, and enrofloxacin, while the highest frequencies of resistant isolates were found for oxytetracycline, streptomycin, doxycycline, ampicillin, amoxicillin, kanamycin, and florfenicol. Furthermore, most isolates (71.4%) showed multiple drug resistance. NGS-based resistome analysis revealed aminoglycoside- and tetracycline-related genes at the highest prevalence, followed by genes related to beta-lactam, sulfamethoxazole, florphenicol, and macrolide. A plasmid replicon (repUS47) and insertion sequences (IS10R and ISVAp11) were identified in resistant isolates. Notably, the multiple resistance roles of the insertion sequence IS10R were widely proposed in human medicine; however, this is the first time IS10R has been reported in veterinary medicine. Concordance analysis revealed a high consistency of phenotypic and genotypic susceptibility to florphenicol, tilmicosin, doxycycline, and oxytetracycline. The current study reports the antimicrobial characterization of A. pleuropneumoniae for the first time in Taiwan using NGS.

Successful guselkumab treatment of a refractory psoriasis patient with Graves' disease: a case report.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

A statistical investigation of parameters associated with low cell-free fetal DNA fraction in maternal plasma for noninvasive prenatal testing.

BACKGROUND: Noninvasive prenatal testing (NIPT) is the most common method for prenatal aneuploidy screening. Low fetal fraction (LFF) is the primary reason for NIPT failure. Consequently, factors associated with LFF should be elucidated for optimal clinical implementation of NIPT. METHODS: In this study, NIPT data from January 2019 to December 2022 from the laboratory records and obstetrical and neonatal data from the electronic medical records were collected and analyzed. Subjects with FF >3.50% were assigned to the control group, subjects with FF <3.50% once were assigned to the LFF group, and subjects with FF <3.50% twice were assigned to the repetitive low fetal fraction (RLFF) group. Factors, including body mass index (BMI), gestational age, maternal age, twin pregnancy, and in vitro fertilization (IVF) known to be associated with LFF were assessed by Kruskal-Wallis H test and logistic regression. Clinical data on first trimester pregnancy-associated plasma protein-A (PAPP-A), beta-human chorionic gonadotropin (ß-hCG), gestational age at delivery, birth weight at delivery, and maternal diseases were obtained from the hospital's prenatal and neonatal screening systems (twin pregnancy was not included in the data on gestational age at delivery and the control group did not include data on maternal diseases.), and were analyzed using Kruskal-Wallis H test and Chi-square test. RESULTS: Among the total of 63,883 subjects, 63,605 subjects were assigned to the control group, 197 subjects were assigned to the LFF group, and 81 subjects were assigned to the RLFF group. The median of BMI in the three groups was 22.43 kg/m2 (control), 25.71 kg/m2 (LFF), and 24.54 kg/m2 (RLFF). The median gestational age in the three groups was 130 days (control), 126 days (LFF), and 122/133 days (RLFF). The median maternal age in the three groups was 29 (control), 29 (LFF), and 33-years-old (RLFF). The proportion of twin pregnancies in the three groups was 3.3% (control), 10.7% (LFF), and 11.7% (RLFF). The proportion of IVF in the three groups was 4.7% (control), 11.7% (LFF), and 21.3% (RLFF). The factors significantly associated with LFF included BMI [2.18, (1.94, 2.45), p < 0.0001], gestational age [0.76, (0.67, 0.87), p < 0.0001], twin pregnancy [1.62, (1.02, 2.52), p = 0.0353], and IVF [2.68, (1.82, 3.86), p < 0.0001]. The factors associated with RLFF included maternal age [1.54, (1.17, 2.05), p = 0.0023] and IVF [2.55, (1.19, 5.54), p = 0.016]. Multiples of the median (MOM) value of ß-hCG and pregnant persons' gestational age at delivery were significantly decreased in the LFF and RLFF groups compared to the control group. CONCLUSION: According to our findings based on the OR value, factors associated strongly with LFF include a high BMI and the use of IVF. Factors associated less strongly with LFF include early gestational age and twin pregnancy, while advanced maternal age and IVF were independent risk factors for a second LFF result.

Body mass index, gestational age, maternal age, twin pregnancy, and in vitro fertilization are associated with fetal fraction. We added the repetitive low fetal fraction population and used a large normal population as a control to identify the main factors associated with low fetal fraction.

[Simulation model of tumor-treating fields].

Tumor-treating fields (TTFields) is a novel treatment modality for malignant solid tumors, often employing electric field simulations to analyze the distribution of electric fields on the tumor under different parameters of TTFields. Due to the present difficulties and high costs associated with reproducing or implementing the simulation model construction techniques, this study used readily available open-source software tools to construct a highly accurate, easily implementable finite element simulation model for TTFields. The accuracy of the model is at a level of 1 mm 3. Using this simulation model, the study carried out analyses of different factors, such as tissue electrical parameters and electrode configurations. The results show that factors influncing the distribution of the internal electric field of the tumor include changes in scalp and skull conductivity (with a maximum variation of 21.0% in the treatment field of the tumor), changes in tumor conductivity (with a maximum variation of 157.8% in the treatment field of the tumor), and different electrode positions and combinations (with a maximum variation of 74.2% in the treatment field of the tumor). In summary, the results of this study validate the feasibility and effectiveness of the proposed modeling method, which can provide an important reference for future simulation analyses of TTFields and clinical applications.

Boosted Sacrificial-Agent-Free Selective Photoreduction of CO2 to CH3OH by Rhenium Atomically Dispersed on Indium Oxide.

Solar-energy-driven photoreduction of CO2 is promising in alleviating environment burden, but suffers from low efficiency and over-reliance on sacrificial agents. Herein, rhenium (Re) is atomically dispersed in In2O3 to fabricate a 2Re-In2O3 photocatalyst. In sacrificial-agent-free photoreduction of CO2 with H2O, 2Re-In2O3 shows a long-term stable efficiency which is enhanced by 3.5 times than that of pure In2O3 and is also higher than those on Au-In2O3, Ag-In2O3, Cu-In2O3, Ir-In2O3, Ru-In2O3, Rh-In2O3 and Pt-In2O3 photocatalysts. Moreover, carbon-based product of the photoreduction overturns from CO on pure In2O3 to CH3OH on 2Re-In2O3. Re promotes charge separation, H2O dissociation and CO2 activation, thus enhancing photoreduction efficiency of CO2 on 2Re-In2O3. During the photoreduction, CO is a key intermediate. CO prefers to desorption rather than hydrogenation on pure In2O3, as CO binds to pure In2O3 very weakly. Re strengthens the interaction of CO with 2Re-In2O3 by 5.0 times, thus limiting CO desorption but enhancing CO hydrogenation to CH3OH. This could be the origin for photoreduction product overturn from CO on pure In2O3 to CH3OH on 2Re-In2O3. The present work opens a new way to boost sacrificial-agent-free photoreduction of CO2.

Cytomorphology of metastatic malignant peripheral nerve sheath tumour present in pleural fluid: Case study and literature review.

The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in pleural effusion. Patients' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses. The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.

The interplay of motor adaptation and groupitizing in numerosity perception: Insights from visual motion adaptation and proprioceptive motor adaptation.

Groupitizing is a well-established strategy in numerosity perception that enhances speed and sensory precision. Building on the ATOM theory, Anobile proposed the sensorimotor numerosity system, which posits a strong link between number and action. Previous studies using motor adaptation technology have shown that high-frequency motor adaptation leads to underestimation of numerosity perception, while low-frequency adaptation leads to overestimation. However, the impact of motor adaptation on groupitizing, and whether visual motion adaptation produces similar effects, remain unclear. In this study, we investigate the persistence of the advantage of groupitizing after motor adaptation and explore the effects of visual motion adaptation. Surprisingly, our findings reveal that proprioceptive motor adaptation weakens the advantage of groupitizing, indicating a robust effect of motor adaptation even when groupitizing is employed. Moreover, we observe a bidirectional relationship, as groupitizing also weakens the adaptation effect. These results highlight the complex interplay between motor adaptation and groupitizing in numerosity perception. Furthermore, our study provides evidence that visual motion adaptation also has an adaptation effect, but does not fully replicate the effects of proprioceptive motor adaptation on groupitizing. In conclusion, our research underscores the importance of groupitizing as a valuable strategy in numerosity perception, and sheds light on the influence of motion adaptation on this strategy.

Deciphering the impact of greenhouse pesticides on hepatic metabolism profile: Toxicity experiments on HepG2 cells using chlorpyrifos and emamectin benzoate.

Epidemiological evidence on the health effects of pesticide exposure among greenhouse workers is limited, and the mechanisms are lacking. Building upon our team's previous population study, we selected two pesticides, CPF and EB, with high detection rates, based on the theoretical foundation that the liver serves as a detoxifying organ, we constructed a toxicity model using HepG2 cells to investigate the impact of individual or combined pesticide exposure on the hepatic metabolism profile, attempting to identify targeted biomarkers. Our results showed that CPF and EB could significantly affect the survival rate of HepG2 cells and disrupt their metabolic profile. There were 117 metabolites interfered by CPF exposure, which mainly affected ABC transporter, biosynthesis of amino acids, center carbon metabolism in cancer, fatty acid biosynthesis and other pathways, 95 metabolites interfered by EB exposure, which mainly affected center carbon metabolism in cancer, HIF-1 signaling pathway, valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis and other pathways. The cross analysis and further biological experiments confirmed that CPF and EB pesticide exposure may affect the HIF-1 signaling pathway and valine, leucine and isoleucine biosynthesis in HepG2 cells, providing reliable experimental evidence for the prevention and treatment of liver damage in greenhouse workers.

Prevalence, outcomes and associated factors of SARS-CoV-2 infection in psoriasis patients of Southwest China: a cross-sectional survey.

In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine's effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

GLI family zinc finger protein 2 promotes skin fibroblast proliferation and DNA damage repair by targeting the miR-200/ataxia telangiectasia mutated axis in diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU.

A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid ß accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.