Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

Yttrium-90 microsphere selective internal radiation therapy (SIRT), also known as transarterial radioembolization, has become one of the pivotal treatments for liver cancer, particularly for selected advantageous patient groups. This review summarizes the characteristics of different patients with liver cancer that could obtain maximum benefit from SIRT and discusses key factors affecting efficacy and safety, including tumor characteristics, liver function, patient performance status, and treatment intent. In evaluating appropriate candidates, mapping serves as a crucial simulation procedure to assess tumor vascular anatomy, predict lung shunting, and guide catheter positioning and dose planning. This procedure substantially enhances therapeutic precision while minimizing the risk of nontarget radiation-related adverse events, such as radiation-induced pneumonitis and gastrointestinal toxicity. Several studies have suggested that SIRT is not only suitable for patients with early or limited hepatocellular carcinoma but can also be used as a bridging therapy for liver transplantation and conversion therapy for unresectable liver cancers. In combination with systemic treatments, SIRT has demonstrated survival benefits in patients with unresectable liver cancer. This review also highlights the importance of further optimizing patient screening through personalized dosimetry and mapping to ensure the precision and safety of treatment. A thorough review of relevant literature and clinical practice offers clinicians comprehensive suggestions on patient screening and clarifies the promise of SIRT in the liver cancer population.

Pathologic myopia(PM)is characterized by progressive axial elongation, posterior staphyloma, and fundus degenerative changes, representing a leading cause of blindness in Asian countries.Posterior scleral reinforcement(PSR)is currently the only surgical intervention to slow axial elongation. Its mechanisms involve mechanical reinforcement, improved blood circulation, and biological stimulation of scleral remodeling. This article reviews recent advances in PSR: surgical techniques have evolved from complex, classic procedures to standardized single-strip methods, incorporating 3D MRI to quantify posterior staphyloma morphology for personalized graft design and facilitating minimally invasive, precision surgery. Among implant materials, biomaterials such as allogeneic dura mater are being continuously optimized, while biomimetic piezoelectric smart materials actively promote scleral collagen synthesis through electrical signals, achieving a paradigm shift from “passive support”to “active reinforcement”. Clinical outcomes indicate advantages in regulating axial length, enhancing visual function and blood circulation, and facilitating early intervention in children. Combined procedures with ICL implantation, cataract surgery or vitrectomy provide comprehensive treatment regimens for individual patients with varied conditions. This article also analyzes long-term issues and core controversies including ectopic posterior staphyloma and reoperation, and prospects future research directions such as artificial intelligence assistance, translation of smart materials and full-cycle prevention and treatment systems, so as to provide references for clinical practice and scientific research.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

OBJECTIVES: To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS: A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h. RESULTS: ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05). CONCLUSIONS ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Microglia/metabolism* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein ; Brain Ischemia/metabolism* ; Male

OBJECTIVES: To investigate the protective mechanism of quercetin, the core component of Zuo Gui Wan, against Alzheimer's disease through the PI3K/AKT signaling pathway, based on network pharmacology, molecular docking, and cell experi-ments. METHODS: The active components of Zuo Gui Wan were identified by searching TCMSP, PubChem, Swiss Target Prediction, and BATMAN-TCM databases, and their potential targets were predicted. The target information was standardized using Uniprot, and Alzheimer's disease-related target genes were obtained from Drugbank, GeneCards, and OMIM. The intersection of these datasets was used to identify the potential targets of Zuo Gui Wan for treating Alzheimer's disease. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The protein-protein interaction (PPI) network of potential targets was visualized using Cytoscape 3.10.1 software and the STRING database. The key active compounds and core potential targets for treating Alzheimer's disease with Zuo Gui Wan were identified through calculation. Based on the enrichment analysis results and literature, quercetin and the PI3K/AKT pathway were selected for verification. Molecular docking and binding ability prediction between quercetin and the core target AKT were performed using CB-Dock2, and visualization was conducted with AutoDock and PyMOL software. Finally, Aβ_1-42-induced HT-22 mouse hippocampal neuronal cells were used to construct an Alzheimer's disease cell model. Quercetin, the PI3K inhibitor LY294002, and the activator EGF were used as interventions. The groups were divided as follows: Control, Aβ_1-42, Aβ_1-42+Quercetin 2.5 μM, Aβ_1-42+Quercetin 5 μM, Aβ_1-42+Quercetin 10 μM, Aβ_1-42+EGF, and the PI3K/AKT modulation group: Control, LY294002, LY294002+Quercetin 10 μM, LY294002+EGF. CCK-8 assays were performed to detect cell viability, while JC-1, Calcein AM-PI, and Hoechst staining were used to assess cell apoptosis. Western blotting was employed to detect the expression of relevant target proteins. RESULTS: Network pharmacology and cell experiments collectively demonstrate that the key active ingredient of Zuo Gui Wan, quercetin, targets core proteins such as AKT1 and GSK3β through a network-based approach, significantly enriching the PI3K/AKT pathway. Molecular docking results indicate that quercetin has a strong binding affinity with AKT. Experimental validation in the Aβ_1-42 oligomer-induced HT-22 model reveals that quercetin significantly activates the PI3K/AKT signaling pathway, which is inhibited by Aβ_1-42 oligomers, as well as Bcl-2 protein expression. It also suppresses the expression of Cleaved Caspase 3/Caspase 3, BAX, and Cytochrome C proteins. JC-1, Hoechst 33342, and Calcein AM-PI staining results further show that quercetin can significantly alleviate apoptosis induced by Aβ_1-42 oligomers in HT-22 cells. Treatment with the PI3K inhibitor LY294002 in HT-22 cells leads to reduced cell viability and decreased expression of p-AKT/AKT and Bcl-2 proteins, while increasing the expression of Cleaved Caspase 3/Caspase 3, BAX, and Cytochrome C proteins. Additionally, apoptosis levels increase as observed in JC-1, Hoechst 33342, and Calcein AM-PI staining, all of which can be reversed by quercetin and the PI3K agonist EGF. CONCLUSIONS Quercetin, the key active ingredient of Zuo Gui Wan, exerts its protective effects against Alzheimer's disease by regulating the PI3K/AKT signaling pathway, inhibiting neuronal cell damage and apoptosis.

OBJECTIVES: This study aimed to explore the potential target and molecular mechanism of Eclipta prostrata L-Ligustrum Lucidum Ait (EPL-LLA) in the treatment of periodontitis by using network pharmacology and molecular docking technology, and to explore its biocompatibility, regulatory effects on inflammatory factors, and antioxidant acti-vity through in vitro experiments. METHODS: The active components and potential targets of EPL-LLA were screened and predicted through a variety of databases, and the intersection of EPL-LLA and periodontitis targets was selected. The protein interaction network (PPI) was analyzed by the string platform. The Metascape database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The active ingredients from the top 6 degrees were docked with the core targets, and the results of binding energy were visualized. An in vitro cell model was established to evaluate the biocompatibility, modulation of inflammatory factors, and antioxidative effects of EPL-LLA through cell counting kit-8 (CCK-8), quantitative real-time polymerase chain reaction (qRT-PCR) and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe assays. RESULTS: Screening revealed 13 active components in EPL corresponding to 220 potential targets, 10 active components in LLA corresponding to 283 potential targets, and 1 643 periodontitis-related targets, with 91 shared targets among the three. GO analysis of the shared targets yielded 5 271 entries, while KEGG enrichment analysis indicated involvement in 253 signaling pathways. Molecular docking confirmed stable binding between the top 6 active components and core targets. CCK-8 assays demonstrated good biocompatibility of EPL-LLA at concentrations 0.02 mg/mL (P<0.05). qRT-PCR showed that EPL-LLA reduced the mRNA expression of pro-inflammatory factors in macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide while upregulating anti-inflammatory factor mRNA expression (P<0.05). DCFH-DA fluorescence probe assays confirmed the reactive oxygen species (ROS)-scavenging capacity of EPL-LLA (P<0.05). CONCLUSIONS EPL-LLA may treat periodontitis through multi-component, multi-target, and multi-pathway mechanisms, providing a theoretical basis for further research on its therapeutic potential.
Periodontitis/drug therapy* ; Molecular Docking Simulation ; Eclipta/chemistry* ; Humans ; Protein Interaction Maps ; Ligustrum/chemistry* ; Antioxidants/pharmacology* ; Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology

BACKGROUND:Liuwei Dihuang Wan takes"three tonifying and three reducing effects"as its compatibility feature to nourish yin and tonify the kidneys,while Zuogui Wan takes"seeking yin in yang"as its compatibility feature to nourish yin and tonify the kidneys by promoting yang.Both of them belong to the same method of nourishing yin and tonifying the kidneys,and have better curative effects at the symptomatic and cellular molecular levels. OBJECTIVE:To observe the effects of Liuwei Dihuang Wan and Zuogui Wan in bone metabolism,and to explore their mechanism of action in the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)osteoblastic pathway. METHODS:Thirty-two Sprague-Dawley rats were randomized into model,Liuwei Dihuang Wan,Zuogui Wan,and sham operation group,with eight rats in each group.Osteoporosis models were prepared using removal of both ovaries in the first three groups.Starting at 30 days postoperatively,rats in the Liuwei Dihuang Wan group were gavaged with Liuwei Dihuang Wan 1.125 g/kg/d;rats in the Zuoqui Wan group were gavaged with Zuogui Wan 2.25 g/kg/d;and rats in the sham operation group and the model group were gavaged with saline 10 mL/kg/d.After 12 weeks of gavage,the rat tibia was taken to measure bone mineral density.The serum levels of estrogen,bone alkaline phosphatase,and cAMP/cGMP were measured using ELISA,and the expression of OPG/RANKL in the femur was detected using western blot. RESULTS AND CONCLUSION:Compared with the sham operation group,the model group showed a decrease in bone mineral density and levels of estrogen and bone alkaline phosphatase(P＜0.05)and an increase in cAMP/cGMP level(P＜0.05).Compared with the model group,the Liuwei Dihuang Wan group and the Zuogui Wan group significantly increased bone mineral density(P＜0.05)and bone alkaline phosphatase levels(P＜0.05);the Zuogui Wan group significantly decreased cAMP/cGMP levels(P＜0.05)and upregulated OPG expression(P＜0.05);the Liuwei Dihuang Wan group upregulated OPG expression and downregulated RANKL expression(P＜0.05);and both groups were unable to significantly increase estrogen levels(P＞0.05).To conclude,Zuogui Wan,which seeks yin from yang,can effectively increase the expression of OPG but cannot downregulate the expression of RANKL.However,Liuwei Dihuang Wan,which has three tonifying and three reducing effects,can bidirectionally regulate the expression of OPG and RANKL.This result suggests that Liuwei Dihuang Wan can significantly inhibit osteoclastic function compared with Zuogui Wan,and further research is needed to verify this conclusion.

BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective:To evaluate the risk of developing pulmonary tuberculosis (PTB) among individuals with latent tuberculosis infection (LTBI) in schools and the protective effect of tuberculosis preventive treatment (TPT).Methods:A retrospective cohort study was conducted to collect data on 15 school outbreaks that occurred in Guangdong Province from 2017 to 2021. Baseline information on tuberculin skin test (TST) or interferon-gamma release test (IGRA) was obtained during contact surveys, as well as baseline information such as TPT. The incidence of PTB between 2017 and 2022 was queried using the Chinese Center for Disease Control and Prevention Information System. Poisson regression analysis was used to compare the incidence risk of PTB in the LTBI population under different TST states at baseline. Current cases, new cases and all cases (the sum of the two) were used as dependent variables. Cox regression models were used to analyze various risk factors affecting the risk of PTB in the LTBI population and evaluate the protective effect of TPT.Results:A total of 6 550 contacts were included in this study, of which 409 received TPT. Within 0-3 months after baseline survey, 119 cases were diagnosed as current cases [19.4‰, 119/(6 550-409)]. A total of 17 221.65 person-years of follow-up were conducted, during which 71 new cases were diagnosed (4.1/1 000 person-years, 71/17 221.65). The incidence density of PTB was 47.7/1 000 person-years, 6.6/1 000 person-years, 1.4/1 000 person-years, and 0.9/1 000 person-years, respectively, in TST strong/IGRA positive, TST moderate positive, TST generally positive, and TST and IGRA negative populations. The difference in PTB incidence density was statistically significant [likelihood ratio test LRT=153.16, P<0.001]. TPT was performed for individuals with strong TST or IGRA positivity, and the protection rate could reach 93% ( HR=0.07, 95% CI: 0.02-0.23). Conclusion:After the outbreak of the school epidemic, individuals with strong TST/IGRA positivity have a higher risk of developing PTB in the future. Targeted implementation of TPT can achieve better protection effects. In addition, the risk of developing PTB in individuals with moderate TST positivity is also worth noting.