Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Current treatment methods for lung cancer primarily include surgery， chemotherapy， targeted therapy， and immunotherapy. However， the main limitations of these treatments are their side effects， the drug resistance， and the economic burden they impose. As a critical cancer pathway， the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway regulates tumor occurrence and development through multiple mechanisms by influencing various downstream targets. Consequently， the JAK/STAT signaling pathway offers a promising avenue for lung cancer treatment research. Numerous studies have demonstrated that the JAK/STAT signaling pathway plays a key role in the proliferation and growth of lung cancer cells， angiogenesis， epithelial-mesenchymal transition （EMT）， metabolic alterations， remodeling of the immune microenvironment， and the development of treatment resistance. Traditional Chinese medicine （TCM） has garnered increasing attention due to its minimal side effects， low economic burden， and its potential to enhance efficacy and reduce toxicity when used in conjunction with Western medicine. In addition to traditional Chinese medicine compounds， a growing number of Chinese medicine monomers have come into the spotlight because of their more targeted effects. Numerous studies investigating the regulation of the JAK/STAT signaling pathway by TCM in the treatment of lung cancer have demonstrated that TCM can inhibit the proliferation and invasion of lung cancer cells， tumor angiogenesis， and EMT， improve the inflammatory and immunosuppressive microenvironments， and enhance treatment sensitivity by intervening in the JAK/STAT signaling pathway， thereby impeding the progression of lung cancer. In recent years， the research on the regulation of this pathway by TCM in the treatment of lung cancer has been updated rapidly. However， the summary of these studies has not been updated in time. This review summarizes and reflects on the recent research findings regarding the regulation of the JAK/STAT signaling pathway by TCM to intervene in lung cancer from three aspects， introducing the JAK/STAT pathway， elaborating the mechanism of this pathway in lung cancer， and exploring the intervention of TCM in the treatment of lung cancer through this pathway， to provide more reference for the treatment of lung cancer in the future.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent cause of chronic liver disease worldwide, and its intricate pathogenesis presents challenges in the development of new drugs. As a common way of post-translational modification, acetylation regulates protein stability, enzyme activity, and subcellular localization, occurring extensively in MASLD-associated processes such as lipid metabolism, inflammatory response, and oxidative stress. In this paper, we comprehensively review the mechanism of acetylation in MASLD, analyze the expression levels of acetylases in liver tissues of MASLD patients from the gene expression omnibus (GEO), discuss the changes in relevant enzyme expression and mechanisms in animal models, and further explore the feasibility of targeting acetylation for MASLD treatment, in the hope of offering a new perspective for advancing drug discovery in the field of MASLD.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Objective:To evaluate the value of preoperative vascular ultrasound parameters in predicting the postoperative lower extremity deep venous thrombosis (DVT) in patients with gynecological malignant tumors.Methods:Ninety-nine patients with gynecological malignant tumors, aged>18 yr, with body mass index<30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were selected. Vascular ultrasound examination was performed before surgery. The flow velocity and diameter of common femoral vein (CFV), deep femoral vein (DFV), popliteal vein (POV), and intermuscular vein (IMV) were recorded. Ultrasound examination of lower limb veins (including anterior tibial vein, posterior tibial vein, IMV, CFV, DFV, POV) were conducted at 1-8 days after surgery to determine whether a DVT occurred. The receiver operating charcateristic curve was used to evaluate the accuracy of each indicator in predicting the lower extremity DVT, and the cut-off value was determined based on the maximum principle of Jorden index. Results:The incidence of lower extremity DVT was 13.1%. The area under the curve (95% confidence interval) of the preoperative CFV flow velocity and diameter, DFV flow velocity and diameter, POV flow velocity and diameter, IMV flow velocity and diameter in predicting the lower extremity DVT were 0.769 (0.616-0.923) and 0.800 (0.644-0.950), 0.797 (0.641-0.954) and 0.771 (0.596-0.945), 0.806 (0.645-0.968) and 0.754 (0.606-0.903), 0.764 (0.615-0.914) and 0.818 (0.645-0.990), respectively ( P<0.05), and the predicted cut-off values were 27.13 cm/s and 11.93 mm, 19.31 cm/s and 10.15 mm, 16.04 cm/s and 8.79 mm, 14.39 cm/s and 8.68 mm, respectively, and the sensitivity and specificity were 90.0%, 71.4% and 90.0%, 74.3%; 90.0%, 74.3% and 90.0%, 68.6%; 90.0%, 82.9% and 90.0%, 72.9%; 90.0%, 70.0% and 80.0%, 87.1%, respectively. Conclusions:Preoperative vascular vascular ultrasound parameters can accurately predict the occurrence of postoperative lower extremity DVT in patients with gynecological malignant tumors.

Objective:To identify the differentially expressed proteins that caused hippocampal damage after liver ischemia-reperfusion (I/R) in rats.Methods:Eighteen clean-grade healthy juvenile male Sprague-Dawley rats, aged 2 weeks, weighing 20-30 g, were divided into 2 groups ( n=9 each) using a random number table method: sham operation group (S group) and liver I/R group (IR group). A rat model of liver I/R injury was prepared by restoring perfusion after 1 h of liver ischemia. The rats were sacrificed after being anesthetized at day 3 of reperfusion, and the hippocampal tissue was isolated and analyzed to obtain gene expression profiles. Differentially expressed genes were identified using the R software, and further protein interaction networks were constructed through Cytoscape and Kyoto Encyclopedia Genes and Genomes pathway analysis to determine the differentially expressed proteins. Quantitative real-time polymerase chain reaction and Western blot were used for validation. Results:A total of 45 differentially expressed proteins were identified by the proteomic analysis of hippocampal tissues, including 36 significantly up-regulated proteins and 9 significantly down-regulated proteins. The proteins with significant expression related to injury were identified from the PPI network complex using the CytoHubBA plug-in cystscape: Ras-related C3 botulinum toxin substrate (RAC2), HRAS, phosphatidylinositol-3-kinase inhibitor phosphatase and tensin homologue (PTEN), and N-methyl-D-aspartate ionotropic glutamate receptor 2b (GRIN2b). The results of quantitative real-time polymerase chain reaction and Western blot showed that the expression of RAC2, HRAS, PTEN, and GRIN2b in the hippocampal tissue was significantly up-regulated in IR group compared with S group ( P<0.05). The results of Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that differentially expressed proteins were significantly enriched in the expression of PD-L1 and its checkpoint pathway, long-term potentiation, and regulation of the Wnt signaling pathway in cancer. Conclusions:The mechanism by which liver I/R induces hippocampal injury may be related to the up-regulation of the expression of RAC2, HRAS, PTEN and GRIN2b in rats.

Objective The study aimed to construct and validate a predictive model for pulmonary nodules(PN)nature based on clinicopa-thological features,imaging,and serum biomarkers,so as to provide scientificdecision-making for early diagnosis and treatment of lung cancer.Methods A retrospective was performed on 816 PN patients with definited pathological diagnosis who received surgical resection analysisor lung biopsy in the Department of Thoracic Surgery and Oncology of Shenzhen Traditional Chinese Medicine Hospital from January 2019 to February 2023.Among them,113 cases that did not meet the inclusion criteria were excluded,and the remaining 703 cases were included in the study.The study based on the clinicopathologic features(age,gender,smoking history,smoking cessation history and family history of cancer),chest imaging(maximum diameter of nodule,location of lesion,clear border,Lobulation,spiculation,vascular convergence sign,vacuole,calcification,air bronchial sign,emphysema,nodule type and pleural indentation,nodule number)and serum carcinoembryonic antigen(CEA),cytokeratin 19 fragment(CYFRA21-1),squamous cell carcinoma antigen(SCCA)in patients with PN.These cases were randomly divided into a modeling group(n=552,237 benign,315 malignant)and a validation group(n=151,85 benign,66 malignant).First,univariate analysis was performed to screen for statistically significant predictors of nodules nature.Then,multivariate regression analysis was performed to screen for independent predictors of nodules nature.Finally,the prediction model of PN nature was constructed by logistic regression analysis.Subsequently,the validation group data were entered into the proposed model and Mayo clinic(Mayo)model,veterans affairs(VA)model,Brock University(Brock)model,Peking University(PKU)model and Guangzhou Medical University(GZMU)model,respectively.PN malignancy probability was calculated.The receiver operating characteristic(ROC)curves were plotted.The diagnostic efficiency of each model was compared according to the area under the curve(AUC).Results There were statistically significant variables including age,family history of cancer,maximum nodule diameter,nodule type,upper lobe of lung,calcification,vascular convergence sign,lobulation,clear border,spiculation,and serum CEA,SCCA,CYFRA21-1 using univariate analysis.Multiple regression analysis showed that age,CEA,clear border,CYFRA21-1,SCCA,upper lobe of lung,maximum nodule diameter,family history of cancer,spiculation and nodule type were independent predictors of PN nature.The prediction model equation constructed in this study is as follows:f(x)= ex/(1+ex),X=(-6.318 8+0.020 8×Age+0.527 4×CEA-0.928 4×clear border+0.294 6×Cyfra21-1+0.294×maximum nodule diameter+1.220 1×family history of cancer +0.573 2×upper lobe of lung +0.064 8×SCCA +1.461 5×Spiculation +1.497 6×nodule type).The AUC(0.799 vs 0.659,0.650)of the proposed model was significantly higher compared with Mayo model and VA model,and there were statistically significant differences(Z=3.029,2.638,P=0.003,0.008).However,compared with Brock model,PKU model and GZMU model,the differences of AUC(0.799 vs 0.762,0.773,0.769)were not statistically significant(Z=1.063,0.686,0.757,P=0.288,0.493,0.449).Conclusion The prediction model for PN nature established in this study is accurate and reliable,which can help clinics with early diagnosis and early intervention,and this prediction model deserves to be popularized.