Protein palmitoylation, a prevalent and dynamic form of S-acylation modification, plays a critical role in maintaining the functionality of the nervous system. This reversible process involves the attachment of palmitic acid to cysteine residues in proteins, anchoring them to cellular membranes and regulating their spatial distribution. The functioning of palmitoylation is crucial for normal neuronal activities, influencing key processes such as signal transduction, synaptic function, and protein trafficking. Recent research has increasingly underscored the significance of specific zinc finger Asp-His-His-Cys motif-containing (ZDHHC) S-acyltransferases in neuronal development and synaptic plasticity. These enzymes, which catalyze the palmitoylation of proteins, have emerged as pivotal regulators of brain function. Dysregulation of palmitoylation by these enzymes is now recognized as a potential contributor to the pathogenesis of various neurodegenerative diseases. This review provides an in-depth analysis of the expression patterns and functional diversity of ZDHHC enzymes across different brain regions and cell types. ZDHHC enzymes exhibit significant sequence variability and demonstrate region-specific and cell type-dependent expression. Such heterogeneity suggests that these enzymes may have specialized roles in different areas of the nervous system, making them crucial modulators of neuronal function and synaptic transmission. The review also explores the regulatory mechanisms of protein palmitoylation and their implications in neurodegenerative disease onset and progression. Altered palmitoylation can lead to the destabilization and subsequent aggregation of these proteins, exacerbating neurodegenerative processes. Abnormal palmitoylation of α‑synuclein can either promote or inhibit its aggregation in Parkinson’s disease pathology. Proteins related to these key pathological factors, including amyloid precursor protein (APP) and beta-secretase 1 (BACE1), are also influenced by palmitoylation, contributing to the formation of amyloid plaques through the aggregation of Aβ. Additionally, ZDHHC13 and ZDHHC17, which are abundantly and widely expressed in the brain, play crucial roles in this process. For instance, reduced interaction between ZDHHC17 and huntingtin could significantly contribute to the pathogenesis of Huntington’s disease. Thus, modulating the palmitoylation status of these proteins presents a promising therapeutic strategy to prevent their toxic aggregation and mitigate neuronal damage. Actually, regulating palmitoylation has shown potential for therapeutic interventions in neurodegenerative diseases, with studies demonstrating that modulation of palmitoylation can restore neuronal function and improve disease symptoms. Regulating palmitoylation holds significant promise for therapeutic strategies in neurodegenerative diseases, as modulation of this process can restore neuronal function and ameliorate disease symptoms. However, progress is hindered by the lack of high-resolution structural data and comprehensive targeting maps for specific ZDHHC enzymes. Additionally, current detection methods for palmitoylation, which focus on labeling and analyzing palmitic acid and cysteine residues, are often complex and time-consuming, and may produce inconsistent palmitoyl-proteomic profiles. These methodological challenges underscore the need for more robust and efficient detection technologies. A deeper understanding of palmitoylation’s role in neurological diseases, coupled with the development of improved detection methods, is essential for advancing our knowledge of the molecular underpinnings of these conditions and for the creation of innovative therapeutic strategies aimed at combating neurodegenerative diseases.

Objective:To retrospectively analyze and study the clinical characteristics, imaging manifestations, laboratory tests, electroencephalography (EEG) results, immunotherapy efficacy, and prognosis of 48 patients with autoimmune encephalitis (AE) in the Hengyang area.Methods:Clinical data of 48 AE patients admitted to the First Affiliated Hospital, the Second Affiliated Hospital, and the Affiliated Nanhua Hospital, University of South China from January 2020 to April 2024 were collected. Retrospective analysis was conducted on age, gender, prodromal symptoms, initial symptoms, main clinical manifestations, cranial magnetic resonance imaging (MRI), electroencephalogram, cerebrospinal fluid routine biochemistry, serum and cerebrospinal fluid antibody detection results, and immunotherapy efficacy.Results:Among the 48 patients, there were 24 males and 24 females, with a median age of onset of 50 years. In terms of clinical manifestations, abnormal mental behavior is the most common initial symptom, accounting for 37.5%(18/48); The next was epileptic seizures, accounting for 35.4%(17/48); 16.7%(8/48) of patients experienced cognitive impairment; Rare initial symptoms included movement disorders, blurred vision, and loss of consciousness. In terms of neuroimaging, 47.9%(23/48) of patients had abnormal signals on cranial MRI, including 47.8%(11/23) of abnormal signals in the temporal lobe or hippocampus, 39.1%(9/23) in the frontal and parietal regions, 17.4%(4/23) in the occipital region, 13.0%(3/23) in the basal ganglia, and 8.7%(2/23) in the thalamus. In terms of EEG, 33.3%(16/48) of patients showed varying degrees of EEG abnormalities, manifested as diffuse slow waves, focal slow waves, epileptic like discharges, or increased fast waves. In terms of laboratory testing, 60.4%(29/48) of patients had routine biochemical abnormalities in cerebrospinal fluid, including elevated white blood cell count (>10×10 6 cells/L) in 33.3%(16/48), elevated protein (>0.45 g/L) in 37.5%(18/48), and elevated IgG in 33.3%(16/48). In terms of antibody testing, 27 cases were positive for antibodies, including 17 cases of N-methyl-D-aspartate receptor (NMDAR) antibody, 3 cases of anti-contactin associated protein 2 (CASPR2) antibody, 3 cases of anti-metabotropic glutamate receptors 5 (mGluR5) antibody, 2 cases of anti-dipeptidyl-peptidase-like protein (DPPX) antibody, 1 case of anti-GlyR antibody, and 1 case of anti-GAD65 antibody. In terms of treatment, 33 patients received immunotherapy on the basis of symptomatic treatment, and 13 of them showed improvement in clinical symptoms. Conclusions:The clinical manifestations of AE patients are highly heterogeneous, with typical initial clinical manifestations including mental abnormalities, epileptic seizures, cognitive and motor disorders. Neuroimaging changes are mainly in the temporal lobe or hippocampus, and antibody detection can timely confirm the diagnosis of AE. Early immunotherapy is the key to improving the prognosis of AE.

AIM:To investigate the effect of tea polyphenols(TP)on the sensitivity of human gastric cancer cells to oxaliplatin(L-OHP)in vitro and its mechanism.METHODS:Human gastric cancer HGC-27 and N87 cells,and human gastric mucosal GES-1 cells were used in this study.The HGC-27 and N87 cells were randomly assigned into con-trol group,TP(5 μmol/L)group,L-OHP(5.2 μmol/L for HGC-27 cells,7.7 μmol/L for N87 cells)group,and TP(5 μmol/L)combined with L-OHP(5.2 μmol/L for HGC-27 cells,7.7 μmol/L for N87 cells)group,with 3 replicate wells per group.The cell viability was detected by CCK-8 assay,and the IC50 value of L-OHP was calculated.The proliferation of the cells was assessed by colony formation assay.The migration and invasion abilities of the cells were evaluated by scratch test and Transwell assay.Flow cytometry was performed to evaluate the antiapoptotic effect of the treatments.Ade-novirus infection was conducted to evaluate cell autophagy.The levels of intracellular reactive oxygen species(ROS)were assessed using a ROS assay kit.Western blot analysis was performed to evaluate the protein expression levels of microtu-bule-associated protein 1 light chain 3(LC3),nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and superoxide dismutase 1(SOD1).RESULTS:Combination of TP and L-OHP significantly reduced the viability of HGC-27 and N87 cells,and markedly inhibited cell proliferation and migration compared with L-OHP alone.Significant increas-es in autophagosomes and ROS levels were observed in combination group compared with L-OHP alone group.The ratio of LC3-II/LC3-I significantly increased in combination group,whereas the expression of Nrf2,HO-1 and SOD1 significantly decreased compared with L-OHP alone group(P<0.05).CONCLUSION:Treatment with TP enhanced the sensitivity of HGC-27 and N87 cells to L-OHP by inhibiting the Nrf2 pathway,promoting the production of intracellular ROS,and in-ducing cell autophagy.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

OBJECTIVE: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. METHODS: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. RESULTS: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC₅₀) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC₅₀ values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC₅₀ values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G₁ phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells. CONCLUSION Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.
Humans ; beta Catenin/metabolism* ; Caco-2 Cells ; Quinones/pharmacology* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Cell Proliferation ; Colorectal Neoplasms/metabolism* ; Cell Line, Tumor ; Apoptosis ; Benzoquinones/pharmacology* ; RNA, Messenger ; Wnt Signaling Pathway

Objective: To investigate the relationship between serum lysophosphatidylcholine (LPC) level and the health index of the elderly. Methods: A total of 251 subjects were selected from the 2016 baseline survey of the Yongfu Longevity Cohort in Guangxi Province among whom 66, 63 and 122 were in the young and middle-aged group (≤59 years old), the young group (60-89 years old) and the longevity group (≥90 years old), respectively. Demographic data were collected and related indicators of height, weight, blood pressure and lipid metabolism were measured. The cognitive and physical functions of the elderly were assessed by the results of the simple mental state scale and the daily living activity scale to construct the health index of the elderly. The serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 were determined by liquid chromatography-tandem mass spectrometry, and the differences among different ages and health status groups were compared. The logistic regression model was used to analyze the relationship between the serum LPC level and the health index of the elderly. Results: With the increase in age, the proportion of female subjects increased, and the rate of smoking and drinking decreased. BMI, TC, TG, LDL-C, diastolic blood pressure, and the four LPCs levels decreased with the increase of age, and systolic blood pressure levels increased with the increase of age (all P values<0.05). There was no significant difference in HDL-C levels among age groups (P>0.05). With the decline of health status in the elderly, serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 showed a downward trend (all P values<0.001). After adjusting for age and gender, only LPC18∶0 was associated with the health status in old age [OR (95%CI): 0.48 (0.25-0.92)]. For every 1 standard deviation (16.87 nmol/L) increase in serum LPC18∶0 concentration, the risk of poor health status in old age decreased by 52%. Conclusion: Serum LPC18∶0 was associated with the health status in old age independent of age and sex.
Aged ; Middle Aged ; Humans ; Female ; Aged, 80 and over ; Lysophosphatidylcholines ; Risk Factors ; China ; Longevity ; Surveys and Questionnaires ; Triglycerides

International research on healthy life expectancy (HALE) focuses on inequality of socioeconomic status and individual natural attributes. With the acceleration of population ageing and the increase in average life expectancy, the extension of unhealthy life expectancy and the increase of social and economic burden caused by diseases have gradually attracted the attention of countries around the world. Therefore, the evaluation of disease factors affecting HALE is a meaningful direction in the future. This study introduces the development process and commonly used measurement methods of HALE. According to the definition of health from the Global Burden of Disease Study and World Health Organization, physical and mental diseases such as cardiovascular and cerebrovascular diseases, chronic respiratory diseases, diabetes, malignant tumors and depression were selected to summarize the impact of these diseases and pre-disease states on HALE. It is expected to provide a theoretical basis for the formulation of relevant public health policies and the improvement of quality of life in China.
Humans ; Healthy Life Expectancy ; Quality of Life ; Life Expectancy ; Causality ; Social Class

Periprosthetic gout flare is a rare arthritic condition after total knee arthroplasty, but the symptoms of gout may have often been mistaken as acute periprosthetic infection given their similarity. Misdiagnosis as periprosthetic infection can lead to unnecessary surgery, long-term dependence on anti-biotics, and even malfunction of the involved knee joint. Here, we report a case study of a patient with immunodeficiency condition of long-term oral glucocorticoid and diabetes mellitus, who had undergone a knee replacement 8 weeks before. The initial symptoms of fever and joint pain together with the dysfunction of her right knee with elevated inflammatory markers, such as increased serum leukocytes, erythrocyte sedimentation rate, C-reactive protein, and synovial cell counts led to a diagnosis of acute periprosthetic infection. Arthrocentesis and bacterial culture were performed preoperatively. According to the current Musculoskeletal Infection Society (MSIS) criteria for diagnosis of periprosthetic infection, the case was classified as periprosthetic infection and a prosthesis retained debridement surgery was performed. However we got negative culture results in all the pre-operative and intro-operative samples. The symptoms as well as the laboratory inflammatory markers improved shortly after the debridement surgery until the 11th day when all the similar systemic and local symptoms recurred. With a remedial crystal analysis of synovial fluid from the patient, gouty flare was found to be the cause of acute arthritis finally. Accor-dingly, after anti-gout medications were administrated, the symptoms associated with acute arthritis gra- dually subsided, and there was no recurrence during a 24-month follow-up. This article described the cli-nical manifestation, diagnosis and differential diagnosis, treatment of a case of periprosthetic gout. Although relatively rare, gout should be considered as a differential diagnosis in suspected periprosthetic infection. Current criteria for periprosthetic infection can not exclude the diagnosis of periprosthetic gout flare, it is therefore imperative that the analysis of joint aspirate for crystals be conducted to determine the correct course of treatment, or unnecessary surgical procedure may be performed in periprosthetic gout case.
Humans ; Female ; Arthroplasty, Replacement, Knee/methods* ; Gout/complications* ; Prosthesis-Related Infections/surgery* ; Symptom Flare Up ; C-Reactive Protein/analysis* ; Biomarkers/analysis*

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
Animals ; Humans ; Male ; Mice ; Rats ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Phosphodiesterase 5 Inhibitors ; Plasminogen Activator Inhibitor 1

OBJECTIVES: To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children. METHODS: Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed. RESULTS: The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (r_s=0.333, P=0.024). CONCLUSIONS JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.
Humans ; Child ; Hypoxia-Inducible Factor 1, alpha Subunit ; Prognosis ; Hypoxia ; Lymphoma, Non-Hodgkin