Integration of network pharmacology and experimental verification to reveal the active components and molecular mechanism of modified Danzhi Xiaoyao San in the treatment of depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. AIM OF THE STUDY: To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. RESULTS: There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. CONCLUSIONS: These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.

Case report: Bridging radiation therapy before chimeric antigen receptor T-cell therapy induces sustained remission in patients with relapsed/refractory double-expressor diffuse large B-cell lymphoma with localized compressive symptoms.

Background: High-risk double-expressor diffuse large B-cell lymphoma has an inferior prognosis following standard first-line therapy. After failure of second-line therapy, treatment options are limited if accompanied by localized compressive symptoms. Chimeric Antigen Receptor T cell (CAR-T) therapy preceded by bridging radiotherapy may be an effective emerging therapy. Case presentation: We report a 66-year-old female patient diagnosed with stage IV double-expressor diffuse large B-cell lymphoma. The patient achieved progressive disease after two cycles of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone and continued to develop cervical lymph node recurrence after second-line therapy. The patient was infused with CAR-T cells after receiving focal bridging radiotherapy and remained in complete response more than 9 months after treatment. In addition, the patients did not experience serious adverse reactions related to radiotherapy as well as CAR-T cell therapy. Conclusions: In this article, we describe a patient with double-expressor diffuse large B-cell lymphoma with localized compression symptoms after second-line treatment failure who benefited from CAR-T combined with focal bridging radiotherapy.

Factors associated with concomitant prostate cancer in benign prostatic hyperplasia patients aged 60 years and above.

OBJECTIVE: Prostate hyperplasia and cancer are more prevalent in middle-aged and elderly men. Previous studies have linked both disorders to androgen receptors. Herein, efforts were made to identify factors associated with prostate cancer in patients ≥60 years, aiming to enhance their health management. METHODS: An analytical framework was established utilizing the "Prostate Cancer Early Warning Dataset" from the National Clinical Medical Science Data Center. Variables selection was conducted through LASSO regression, followed by multifactorial logistic stepwise regression to construct a predictive model. RESULTS: A total of 1,502 patients with BPH and 294 with combined PCa were hereby included. Multivariate regression delineated several independent predictors of PCa coexistence, including age (OR [95% CI]: 1.06 [1.04-1.09], p < 0.001), fPSA/tPSA ratio (OR [95% CI]: 0.01 [0.002-0.05], p < 0.001), serum inorganic phosphorus (OR [95% CI]: 5.85 [2.61-13.15], p < 0.001), globulin levels (OR [95% CI]: 1.06 [1.02-1.11], p = 0.005), serum potassium (OR [95% CI]: 0.58 [0.40-0.86], p = 0.006), low-density lipoprotein (LDL) cholesterol (OR [95% CI]: 1.28 [1.06-1.54], p = 0.009), among others. CONCLUSION: The analysis revealed connections between PCa occurrence in men aged over 60 and BPH, along with specific serum biomarkers such as inorganic phosphorus, globulin, LDL cholesterol, lower fPSA/tPSA ratios and serum potassium.

Modular Assembly of Pyrrolo[3,4-c]isoquinolines through Rh-Catalyzed Cascade C-H Activation/Annulation of O-Methyl Aryloximes with Maleimides.

An efficient and practical strategy for the construction of pyrrolo[3,4-c]isoquinolines via Rh(III)-catalyzed cascade C-H activation and subsequential annulation process from easily available O-methyl aryloximes and maleimides has been disclosed. This facile protocol does not require any inert atmosphere protection with good efficiency in a low loading of catalyst and exhibits good functional group tolerance and broad substrate scope. Notably, the as-prepared products show potential photophysical properties.

Diamino-functionalized metal-organic framework for selective capture of gold ions.

Adsorptive recovery of valuable gold (Au) ions from wastes is vital but still challenged, especially regarding adsorption capacity and selectivity. A novel M - 3,5-DABA metal-organic framework (MOF) adsorbent was prepared via anchoring 3,5-diaminobenzoic acid (3,5-DABA) molecule in the MOF-808 matrix. Benefiting from the positive charge property, dense amino groups (3.2 mmol g-1) and high porosity, the adsorption capacity of M - 3,5-DABA reaches 1391.5 mg g-1 (pH = 2.5) and adsorption equilibrium is attained in 5 min. This amino-based material shows excellent selectivity towards various metal ions, evading the poor selectivity problem of classical thiol groups (e.g. for Ag+, Cu2+, Pb2+ and Hg2+ ions). In addition, the regeneration was easily achieved via using a hydrochloric acid-thiourea eluent. Experimental analysis and density functional theory (DFT) calculation show the amino group works as a reductant for Au(III) ions and meanwhile acts as an active site for adsorbing Au(III) ions together with the µ-OH group. Thus, M - 3,5-DABA can act as a potential adsorbent for Au(III) ions, and our work offers a viable strategy to construct novel MOF-based adsorbents.

Unveiling the role of AGT in lipid metabolism and regulated cell death in colon cancer.

BACKGROUND: Lipid metabolism and regulated cell death (RCD) play a role in the remodeling of tumor immune microenvironment and regulation of cancer progression. Since the underlying immune mechanisms of colon cancer remain elusive, this study aims to identify potential therapeutic target genes. METHODS: Differential genes related to lipid metabolism and RCD in COAD patients were identified using R language and online tools. Based on the expression of genes, two groups were classified using consensus clustering. CIBERSORT and ssGSEA were used to detect immune infiltration in both groups. Prognostic signature genes for colon cancer were screened using machine learning algorithms. KEGG, GO and GSEA for gene pathway enrichment. In addition, interacting genes in the immune module were obtained using a weighted gene co-expression network (WGCNA). Finally, expression and mutation of key in colon cancer genes were detected using TIMER, HPR, cBioPortal website and qPCR. RESULTS: The consensus clustering analysis revealed that 231 relevant differential genes were highly associated with immune infiltration. A series of machine learning and website analyses identified AGT as a hub gene linked to lipid metabolism and regulated cell death, which is overexpressed in colon cancer. CONCLUSION: AGT, as a signature gene of lipid metabolism and regulated cell death, plays a critical role in the development of COAD and is associated with tumor immune infiltration.

Effects of different sodium-glucose cotransporter 2 inhibitors in heart failure with reduced or preserved ejection fraction: a network meta-analysis.

Background: This systematic review and meta-analysis aimed to explore the effects of different sodium-glucose cotransporter-2 inhibitors (SGLT2i) on prognosis and cardiac structural remodeling in patients with heart failure (HF). Methods: Relevant studies published up to 20 March 2024 were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library CNKI, China Biomedical Literature Service, VIP, and WanFang databases. We included randomized controlled trials of different SGLT2i and pooled the prognosis data of patients with HF. We compared the efficacy of different SGLT2i in patients with HF and conducted a sub-analysis based on left ventricular ejection fraction (LVEF). Results: We identified 77 randomized controlled trials involving 43,561 patients. The results showed that SGLT2i significantly enhanced outcomes in HF, including a composite of hospitalizations for HF and cardiovascular death, individual hospitalizations for HF, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, left atrial volume index (LAVi), and LVEF among all HF patients (P < 0.05) compared to a placebo. Sotagliflozin was superior to empagliflozin [RR = 0.88, CI (0.79-0.97)] and dapagliflozin [RR = 0.86, CI (0.77-0.96)] in reducing hospitalizations for HF and CV death. Dapagliflozin significantly reduced hospitalizations [RR = 0.51, CI (0.33-0.80)], CV death [RR = 0.73, CI (0.54-0.97)], and all-cause mortality [RR = 0.69, CI (0.48-0.99)] in patients with HF with reduced ejection fraction (HFrEF). SGLT2i also plays a significant role in improving cardiac remodeling and quality of life (LVMi, LVEDV, KCQQ) (P < 0.05). Among patients with HF with preserved ejection fraction (HFpEF), SGLT2i significantly improved cardiac function in HFpEF patients (P < 0.05). In addition, canagliflozin [RR = 0.09, CI (0.01-0.86)] demonstrated greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF patients. Conclusion: Our systematic review showed that SGLT2i generally enhances the prognosis of patients with HF. Sotagliflozin demonstrated superiority over empagliflozin and dapagliflozin in a composite of hospitalization for HF and CV death in the overall HF patients. Canagliflozin exhibited greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF. Overall, the efficacy of SGLT2i was greater in HFrEF patients than in HFpEF patients.

Modified Danzhi XiaoyaoSan inhibits neuroinflammation via regulating TRIM31/NLRP3 inflammasome in the treatment of CUMS depression.

The NLRP3 inflammasome is critically involved in the development of depression. The E3 ubiquitin ligase TRIM31 negatively regulates this process by promoting the degradation of NLRP3 through the ubiquitin-proteasome pathway. Modified Danzhi Xiaoyaosan (MDZXYS) has shown good therapeutic effect in both preclinical and clinical depression treatments, yet the underlying mechanisms of its antidepressant effects are not fully understood. In the present study, we aimed to explore the antidepressant mechanisms of MDZXYS, focusing on NLRP3 activation and ubiquitin-mediated degradation. We employed rats with depression induced by chronic unpredictable mild stress (CUMS) and conducted various behavioral tests, including the sucrose preference, forced swimming, and open field tests. Neuronal damage in CUMS-treated rats was assessed using Nissl staining. We measured proinflammatory cytokine levels using ELISA kits and analyzed NLRP3/TRIM31 protein expression via Western blotting and immunofluorescence staining. Our results disclosed that MDZXYS reversed CUMS-induced depression-like behaviors in rats, reduced proinflammatory cytokine levels (IL-1ß), and ameliorated neuronal damage in the prefrontal cortex. Additionally, CUMS activated the NLRP3 inflammasome in the prefrontal cortex and upregulated the protein expression of TRIM31. After MDZXYS administration, the expression of NLRP3 inflammasome-associated proteins was reduced, while the expression level of TRIM31 was further increased. Through co-localized immunofluorescence staining, we observed a significant elevation in the co-localization expression of NLRP3 and TRIM31 in the prefrontal cortex of the MDZXYS group. These findings suggest that inhibiting NLRP3 inflammasome-mediated neuroinflammation by modulating the TRIM31signaling pathway may underlie the antidepressant effects of MDZXYS, and further support targeting NLRP3 as a novel approach for the prevention and treatment of depression.

A rhodium-catalyzed cascade C-H activation/annulation strategy for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines.

A cascade annulation strategy triggered by rhodium(III)-catalyzed C-H activation has been reported for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines from free NH-sulfoximines with maleimides under mild conditions. Without the need for inert atmosphere protection, a broad range of sulfoximines with maleimides were well tolerated, producing diverse fused-thiazine derivatives in moderate to good yields. Additionally, the late-stage transformation of the target product demonstrated the potential synthetic value of this protocol.

Integrating land-sea coordination into construction of an ecological security pattern for urban agglomeration: a case study in the Guangdong-Hong Kong-Macao Greater Bay Area.

The construction of ecological security pattern (ESP) is of great scientific significance for solving the problem of habitat fragmentation in urban environment. However, previous studies mainly focused on the ESP in land area, leaving the sea area to be ignored. This study took the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) and its offshore area as an example and integrated the land-sea coordination into the construction of ESP based on the minimum resistance model, gravity model, and graph theory centrality. The results showed that there are 171 and 56 ecological sources for land area and offshore area, accounting for 31.46% and 21.51% of total area, respectively. Twenty-four important ecological corridors with a total length of 2738.05 km were identified in GBA, and the width is proposed to be less than 100 m. Moreover, the α, ß, and γ index of the ecological network in the study area is 0.19, 1.33, and 0.5, respectively, indicating that the ecological network structure is complex and the connectivity between ecological nodes is good. The ecological restoration area includes 286.6 km2 of ecological pinch points and 140.44 km2 of ecological barrier. The overall ESP of the study area is "one ring, two belts, and four zones." The main body of the area with a superior ecological environment is distributed in a ring-like pattern near the outer edge of the study area, and two belts (important ecological corridor and ecological corridor) are distributed in a network. According to the ecological characteristics, the study area was divided into four zones: ecological preservation areas, ecological restoration areas, limited construction areas, and optimized construction areas. The ESP established herein institute provides a reference for the revision of ecological space control and optimization measures in the GBA. It also provides effective and systematic means to solve ecological problems in the current territorial spatial planning and territorial ecological restoration of coastal urban agglomeration.

Synthesis of arene-functionalized fused heterocyclic scaffolds via a regioselective cascade 1,4-conjugate addition/5-exo-dig annulation strategy.

Facile access to furan fused heterocyclic scaffolds through a regioselective cascade reaction of propargylamines with 4-hydroxy-2H-pyran-2-ones and 4-hydroxy-6-methylpyridin-2(1H)-one has been achieved. This cascade reaction presumably involves the formation of ortho-alkynyl quinone methide (o-AQM), 1,4-conjugate addition, followed by regioselective 5-exo-dig annulation, and a 1,3-H shift process. Moreover, the reaction provides a new and efficient method for the synthesis of highly sterically congested 3-phenolic furo[3,2-c]pyran-4-ones and furo[3,2-c]pyridin-4(5H)-ones by the formation of a furan ring from readily available starting materials in good to high yields (50-82%) with broad functional group compatibility in a single step. Significantly, the strategy described here is easily scalable and several useful synthetic transformations of the prepared arene-functionalized 4H-furo[3,2-c]pyran-4-ones were also performed.

Cascade Annulation Strategy for Expeditious Assembly of Hydroxybenzo[c]chromen-6-ones and Their Photophysical Property Studies.

A 1,8-diazabicyclo[5.4.0]undec-7-ene-promoted cascade double-annulation of ortho-alkynyl quinone methide (in situ generated from modular propargylamine) for constructing of 2-aryl-4-hydroxybenzo[c]chromen-6-ones is developed. This synthetic strategy offers remarkable operational simplicity as it allows the use of benchtop-grade solvents without the need for predrying measures and inert atmosphere protection. Additionally, it demonstrates good functional group compatibility. The photophysical properties of these compounds were also examined, revealing bright fluorescence with high quantum yields.

LINC00922 decoys SIRT3 to facilitate the metastasis of colorectal cancer through up-regulation the H3K27 crotonylation of ETS1 promoter.

BACKGROUND: Lysine crotonylation (Kcr) is up-regulation in colorectal cancer (CRC) tissues, while its specific contribution remains uncertain. This study aimed to elucidate the role and mechanism of crotonylation on Lys27 of histone H3 (H3K27cr) in facilitating CRC metastasis. METHODS: Immunohistochemistry was employed to investigate the correlation between H3K27cr and CRC metastasis. Both in vitro and in vivo assays employing loss function or gain function approaches were conducted to elucidate the role of LINC00922 in promoting CRC metastasis. ScRNA-seq analysis and immunoprecipitation analyses were employed to explore the underlying mechanism by which LINC00922 facilitates CRC metastasis through H3K27cr. RESULTS: Clinically, H3K27cr was upregulated in metastatic CRC tissues and positively correlated with advanced clinical stages. Functionally, knockdown of LINC00922 inhibited migration of CRC cells both in vitro and in vivo. Furthermore, the supplementation of NaCr restored the migration and invasion levels of LINC00922 stable knockdown cells by restoring the H3K27cr level. Mechanistically, LINC00922 promoted invasion and migration through H3K27cr mediated cell adhesion molecules (CAMs) in epithelial cells. Notably, LINC00922 interacted with the protein sirtuin 3 (SIRT3) and obstructed its binding to the promoter region of ETS1, leading to an elevation in the level of H3K27cr in this promoter region and the subsequent activation of ETS1 transcription. CONCLUSIONS: Our findings uncovered a novel regulatory function of H3K27cr, regulated by LINC00922, in facilitating CRC metastasis. This discovery contributed to a deeper comprehension of the involvement of histone crotonylation in the metastatic process of CRC.

Exploring the efficient natural products for Alzheimer's disease therapy via Drosophila melanogaster (fruit fly) models.

Alzheimer's disease (AD) is a grievous neurodegenerative disorder and a major form of senile dementia, which is partially caused by abnormal amyloid-beta peptide deposition and Tau protein phosphorylation. But until now, the exact pathogenesis of AD and its treatment strategy still need to investigate. Fortunately, natural products have shown potential as therapeutic agents for treating symptoms of AD due to their neuroprotective activity. To identify the excellent lead compounds for AD control from natural products of herbal medicines, as well as, detect their modes of action, suitable animal models are required. Drosophila melanogaster (fruit fly) is an important model for studying genetic and cellular biological pathways in complex biological processes. Various Drosophila AD models were broadly used for AD research, especially for the discovery of neuroprotective natural products. This review focused on the research progress of natural products in AD disease based on the fruit fly AD model, which provides a reference for using the invertebrate model in developing novel anti-AD drugs.

Substituent-Controllable Cascade Regioselective Annulation of ß-Enaminones with N-Sulfonyl Triazoles for Modular Access to Imidazoles and Pyrroles.

A controllable synthesis of trisubstituted imidazoles and pyrroles has been developed through rhodium(II)-catalyzed regioselective annulation of N-sulfonyl-1,2,3-trizaoles with ß-enaminones. The imidazole ring was formed through a 1,1-insertion of the N-H bond to α-imino rhodium carbene, followed by a subsequent intramolecular 1,4-conjugate addition. This occurred when the α-carbon atom of the amino group was bearing a methyl group. Additionally, the pyrrole ring was constructed by utilizing a phenyl substituent and undergoing intramolecular nucleophilic addition. The mild conditions, good tolerance towards functional groups, gram-scale synthesis capability, and ability to undergo valuable transformations of the products qualify this unique protocol as an efficient tool for the synthesis of N-heterocycles.

Clonal integration promotes the growth of Phragmites australis populations in saline wetlands of the Yellow River Delta.

Estuarine wetlands are highly heterogeneous due to strong interactions between freshwater input and seawater intrusion. However, little is known about how clonal plant populations adapt to heterogeneous salinity in soil environments. In the present study, the effects of clonal integration on Phragmites australis populations under salinity heterogeneity were studied using field experiments with 10 treatments in the Yellow River Delta. Clonal integration significantly increased plant height, aboveground biomass, underground biomass, root-shoot ratio, intercellular CO2 concentration, net photosynthetic rate, stomatal conductance, transpiration rate, and stem Na+ content under homogeneous treatment. Under the heterogeneous salt treatment, clonal integration significantly affected total aboveground and underground biomass, photosynthetic traits, and stem Na+ content under different salt gradients. The increase in salt concentration inhibited the physiological activity and growth of P. australis to varying degrees. Compared with the heterogeneous saline environment, clonal integration was more beneficial to P. australis populations in the homogeneous saline habitat. The results of the present study suggest that P. australis prefers homogeneous saline habitats; however, plants can adapt to heterogeneous salinity conditions via clonal integration.

Identification of prognostic melatonin-related lncRNA signature in tumor immune microenvironment and drug resistance for breast cancer.

BACKGROUND: Melatonin is a neurohormone involved in diverse physiological processes, including regulation of circadian rhythm, oncogenesis and immune function. More attention are focused on the molecular events surrounding the occurrence of abnormally expressed lncRNAs leading to breast cancer. The purpose of this study was to evaluate the role of melatonin-related lncRNAs in the clinical management of BRCA patients and their immune responses. METHODS: The transcriptome data and clinical data of BRCA patients were acquired from TCGA database. A total of 1103 patients were randomly assigned to either training set or validation set. A melatonin-related lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis, immune microenvironment and drug resistance analysis associated to melatonin-related lncRNAs were performed by utilizing GO&KEGG, ESTIMATE and TIDE analysis. A nomogram based on the signature score and clinical characteristics was established, which was calibrated to increase prediction probability of 1-year, 3-year and 5-year survival for BRCA patients. RESULTS: BRCA patients were divided into two signature groups based on a 17-melatonin-related lncRNA signature. High-signature patients had worse prognosis than low-signature patients (p < 0.001). Univariate and multivariate Cox regression analysis proved that the signature score was an independent prognostic factor for BRCA patients. Functional analysis indicated that high-signature BRCA involved in regulation of processing and maturation of mRNA and misfolded protein response. Remarkably, immune microenvironment analysis showed that the proportion of tumor-infiltrating M2 macrophage and the expression of CTLA4 were significantly higher in high-signature BRCA. The calibration curves for the probability of invasive BRCA showed optimal agreement between the probability as predicted by the nomogram and the actual probability. CONCLUSIONS: A novel melatonin-related lncRNA signature was considered as an independent prognostic indicator for BRCA patients. Melatonin-related lncRNAs were potentially associated with tumor immune microenvironment and might be therapeutic targets for BRCA patients.

The water extract of Potentilla discolor Bunge (PDW) ameliorates high-sugar diet-induced type II diabetes model in Drosophila melanogaster via JAK/STAT signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla discolor Bunge (PD) is a member of the Rosaceae family. It has been traditionally used in folk medicine for the treatment of diabetes. Additionally, people in folk also eat fresh and tender PD stems as vegetables or brew them as tea. AIM OF THE STUDY: The aim of this study was to explore the antidiabetic effects and underlying mechanisms of the water extract of Potentilla discolor (PDW) in a fruit fly model of high-sugar diet-induced type 2 diabetes. MATERIALS AND METHODS: The antidiabetic efficacy of PDW was evaluated in a fruit fly model of diabetes induced by a high-sugar diet (HSD). Various physiological parameters were tested to evaluate the anti-diabetic effect of PDW. Gene expression levels related to insulin signaling pathways, glucose metabolism, lipid metabolism, and JAK/STAT signaling pathways were primarily analyzed using RT-qPCR to investigate the therapeutic mechanisms. RESULTS: In this study, we found that the water extract of Potentilla discolor (PDW) can ameliorate type II diabetes phenotypes induced by the HSD in fruit flies. These phenotypes include growth rate, body size, hyperglycemia, glycogen metabolism, fat storage, and intestinal microflora homeostasis. PDW also improved the body size of s6k and rheb knockdown flies, suggesting its potential to activate the downstream insulin pathway and alleviate insulin resistance. Furthermore, we demonstrated that PDW reduced the expression of two target genes of the JAK/STAT signaling pathway, namely the insulin antagonist Impl2 and insulin receptor inhibitor Socs36E, which act as regulators inhibiting the activation of the insulin signaling pathway. CONCLUSIONS: This study provides evidence for the anti-diabetic activity of PDW and suggests that its underlying mechanism may involve the improvement of insulin resistance by inhibiting the JAK/STAT signaling pathway.

Modified Xiaoyao San reverses lipopolysaccharide-induced depression-like behavior through suppressing microglia M1 polarization via enhancing autophagy involved in PI3K/Akt/mTOR pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Xiaoyao San (MXYS), a clinical empirical modified formula based on famous traditional Chinese herbal prescription Xiaoyao San, according to the "yu syndrome" theory of traditional Chinese medicine. MXYS has been shown to be an excellent effective therapy for depression patients in clinic, but the antidepressant mechanisms remain unclear. AIM OF THE STUDY: A growing body of evidence indicates the microglia autophagy and M1 polarized microglia (proinflammatory phenotype)-mediated neuroinflammation act critical roles in the pathogenesis of depression. This study aimed to investigate whether MXYS exerts antidepressant efficacy through inhibition of M1 polarized microglia-mediated neuroinflammation and modulation of autophagy involved in PI3K/Akt/mTOR pathway. MATERIALS AND METHODS: In present research, the lipopolysaccharide (LPS)-induced depressive mice and LPS-stimulated N9 microglia cell line were utilized. Behavioral tests (sucrose preference, tail suspension and open field tests) were carried out to evaluate the antidepressant effect of MXYS. The neuronal damage was measured by Nissl's staining in LPS-treated mice. The proinflammatory cytokine levels, the autophagic markers, microglia M1 polarization as well as the PI3K/Akt/mTOR pathway related proteins of MXYS treatment were analyzed by ELISA kits, Western blot and immunofluorescence staining in vivo and vitro. Finally, the influence of autophagy antagonist (3-MA) on the protective effect of MXYS-containing serum in the LPS-stimulated N9 microglia was investigated. RESULTS: Treatment of LPS-induced depressive mice with MXYS significantly reversed depression-like behaviors, accompanied by reduction of proinflammatory cytokine levels (TNF-α, IL-1ß) and amelioration of neuronal damage in prefrontal cortex. MXYS suppressed microglia M1 polarization and promoted autophagy in prefrontal cortex and LPS-stimulated N9 cells. Importantly, the remarkable inhibitory effect of the MXYS-medicated serum on microglia M1 polarization was blocked by autophagy antagonist 3-MA in LPS-stimulated N9 cells. Meanwhile, the MXYS treatment exhibited an excellent inhibition effect of PI3K/Akt/mTOR pathway in vivo and vitro. CONCLUSION: Our research suggests that the antidepressant effect of MXYS in LPS-induced depressive mice may be related to alleviate neuroinflammation through suppression of microglia M1 polarization via enhancing autophagy involved in inactivation of the PI3K/Akt/mTOR pathway.

Identification of S100A9 as a Potential Inflammation-Related Biomarker for Radiation-Induced Lung Injury.

Radiation-induced lung injury (RILI), a potentially fatal and dose-limiting complication of radiotherapy for thoracic tumors, is divided into early reversible pneumonitis and irreversible advanced-stage fibrosis. Early detection and intervention contribute to improving clinical outcomes of patients. However, there is still a lack of reliable biomarkers for early prediction and clinical diagnosis of RILI. Given the central role of inflammation in the initiation and progression of RILI, we explored specific inflammation-related biomarkers during the development of RILI in this study. Two expression profiles from the Gene Expression Omnibus (GEO) database were downloaded, in which 75 differentially expressed genes (DEGs) were screened out. Combining Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis, we identified four inflammation-related hub genes in the progression of RILI-MMP9, IL-1ß, CCR1 and S100A9. The expression levels of the hub genes were verified in RILI mouse models, with S100A9 showing the highest level of overexpression. The level of S100A9 in bronchoalveolar lavage fluid (BALF) and the expression of S100A9 in lung tissues were positively correlated with the degree of inflammation in RILI. The results above indicate that S100A9 is a potential biomarker for the early prediction and diagnosis of the development of RILI.