Glucocorticoid receptors involved in ginsenoside compound K ameliorate adjuvant arthritis by inhibiting the glycolysis of fibroblast-like synoviocytes via the NF-κB/HIF-1α pathway.

CONTEXT: Ginsenoside metabolite compound K (CK) is an active metabolite produced by ginsenosides in vivo that has an anti-arthritic effect related to the glucocorticoid receptor (GR). However, the potential mechanisms of CK remain unclear. OBJECTIVE: This study explores the role and potential mechanisms of CK in vivo and in vitro. MATERIALS AND METHODS: Adjuvant arthritis (AA) model was induced in Sprague-Dawley (SD) rats; the rats were randomly divided into four groups (n = 10): normal, AA, CK (80 mg/kg), and dexamethasone (Dex) group (1 mg/kg). From day 15, rats were treated with CK (once a day, i.g.) and Dex (once every 3 days, i.p.) for 18 days. To further verify the mechanism of CK, fibroblast-like synoviocytes (FLS) were stimulated by tumour necrosis factor α (TNF-α) to establish an inflammatory model in vitro. RESULTS: CK (80 mg/kg) reduced paw swelling (52%) and arthritis global assessment (31%) compared to that in AA rats. In addition, CK (80 mg/kg) suppressed GLUT1 (38%), HK2 (50%), and PKM2 (56%) levels compared with those in AA FLS. However, the effects of CK (30 µM) on these events were weakened or enhanced after GR knockdown or overexpression in FLS stimulated by TNF-α (30 ng/mL). CK (80 mg/kg) also downregulated the expression of P65 (61%), p-IκB (92%), and HIF-1α (59%). DISCUSSION AND CONCLUSIONS: The inhibition of CK on glycolysis and the NF-κB/HIF-1α pathway is potentially mediated through activating GR. These findings provide experimental evidence for elucidating the molecular mechanism of CK in treating rheumatoid arthritis (RA).

Four Chemotherapeutic Compounds That Limit Blood-Brain-Barrier Invasion by Toxoplasma gondii.

BACKGROUND: Toxoplasma gondii, an intracellular protozoan parasite, exists in the host brain as cysts, which can result in Toxoplasmic Encephalitis (TE) and neurological diseases. However, few studies have been conducted on TE, particularly on how to prevent it. Previous proteomics studies have showed that the expression of C3 in rat brains was up-regulated after T. gondii infection. METHODS: In this study, we used T. gondii to infect mice and bEnd 3 cells to confirm the relation between T. gondii and the expression of C3. BEnd3 cells membrane proteins which directly interacted with C3a were screened by pull down. Finally, animal behavior experiments were conducted to compare the differences in the inhibitory ability of TE by four chemotherapeutic compounds (SB290157, CVF, NSC23766, and Anxa1). RESULTS: All chemotherapeutic compounds in this study can inhibit TE and cognitive behavior in the host. However, Anxa 1 is the most suitable material to inhibit mice TE. CONCLUSION: T. gondii infection promotes TE by promoting host C3 production. Anxa1 was selected as the most appropriate material to prevent TE among four chemotherapeutic compounds closely related to C3.

Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses.

BACKGROUND: The life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions. RESULT: In the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.

Deciphering the epidemiological dynamics: Toxoplasma gondii seroprevalence in mainland China's food animals, 2010-2023.

Background: Toxoplasma gondii (T. gondii) is a significant protozoan pathogen among food animals. Despite the threat to public health by T. gondii infections, there's limited understanding of its seroprevalence and trends in food animals across mainland China. This study aimed to estimate the seroprevalence of T. gondii infections among swine, sheep, goats, chickens, and cattle in mainland China from 2010 to 2023. Methods: We searched cross-sectional studies published between 2010 and 2023 that reported the prevalence of T. gondii in food animals from databases including PubMed, Embase, Web of Science, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang data, and the China Science and Technology Journal Database (CQVIP). We performed subgroup analyses to explore the impact of different factors on the seroprevalence of T. gondii. Pooled estimates of T. gondii seroprevalence were calculated with a random-effects model. Results: An analysis of 184 studies involving 211985 animals revealed a T. gondii overall seroprevalence of 15.3% (95% CI: 13.1-17.8). Although the seroprevalence of food animals across mainland China was relatively stable from 2010 to 2023, notable variations were observed across different animal types and regions (P < 0.01), along with changes in geographical distribution. Sample type, detection method, animal age, and history of abortion were identified as key risk factors for T. gondii seroprevalence. Conclusion: The study conducted a meta-analysis on the seroprevalence of T. gondii in mainland China's Food Animals from 2010 to 2023, and identified key risk factors. These findings advance our understanding of T. gondii infection dynamics, offering critical insights for developing control strategies and guiding public health policies.

Evaluating the spatial accessibility and spatial layout optimization of HIV/AIDS healthcare services in Shandong Province, China.

Improving access to HIV/AIDS healthcare services is of great concern to government and policymakers striving to strengthen overall public health. How to reasonably allocate HIV/AIDS healthcare resources and maximize the equality of access to healthcare services across subdistrict areas has become an urgent problem to be solved. However, there is limited research on this topic in China. It is necessary to evaluate spatial accessibility to improve the accessibility and equity of HIV/AIDS healthcare services. In this study, the improved multi-modal two-step floating catchment area (2SFCA) and inverted 2SFCA (i2SFCA) methods are used to measure the spatial accessibility of HIV/AIDS healthcare services and the crowdedness of the healthcare sites in Shandong Province, China. Then, the theoretical supply and the optimal spatial distribution of resources are calculated and visualized by minimizing the accessibility gaps between demand locations. This study showed that the spatial accessibility of HIV/AIDS service resources in Shandong Province was concentrated and unevenly distributed, and the accessibility scores in the marginal areas of prefecture-level cities were significantly lower than those in other areas. Regions with a large number of doctors had significantly higher levels of spatial accessibility. The ART accessibility scores in the southwest of Shandong Province were higher than those in other regions. As the travel friction coefficient increased, the accessibility scores formed an approximately circular cluster distribution centered on the healthcare sites in geographical distribution. More ART drugs needed to be supplied in marginal areas and more doctors were needed to work on HIV/AIDS in urban areas to address the spatial distribution imbalance of HIV/AIDS healthcare services. This study profoundly analyzed the spatial accessibility of HIV/AIDS healthcare services and provided essential references for decision-makers. In addition, it gives a significant exploration for achieving the goal of equal access to HIV/AIDS healthcare services in the future.

The opposing effect of acute and chronic Toxoplasma gondii infection on tumor development.

BACKGROUND: The interplay between Toxoplasma gondii infection and tumor development is intriguing and not yet fully understood. Some studies showed that T. gondii reversed tumor immune suppression, while some reported the opposite, stating that T. gondii infection promoted tumor growth. METHODS: We created three mouse models to investigate the interplay between T. gondii and tumor. Model I aimed to study the effect of tumor growth on T. gondii infection by measuring cyst number and size. Models II and III were used to investigate the effect of different stages of T. gondii infection on tumor development via flow cytometry and bioluminescent imaging. Mouse strains (Kunming, BALB/c, and C57BL/6J) with varying susceptibilities to tumors were used in the study. RESULTS: The size and number of brain cysts in the tumor-infected group were significantly higher, indicating that tumor presence promotes T. gondii growth in the brain. Acute T. gondii infection, before or after tumor cell introduction, decreased tumor growth manifested by reduced bioluminescent signal and tumor size and weight. In the tumor microenvironment, CD4+ and CD8+ T cell number, including their subpopulations (cytotoxic CD8+ T cells and Th1 cells) had a time-dependent increase in the group with acute T. gondii infection compared with the group without infection. However, in the peripheral blood, the increase of T cells, including cytotoxic CD8+ T cells and Th1 cells, persisted 25 days after Lewis lung carcinoma (LLC) cell injection in the group with acute T. gondii. Chronic T. gondii infection enhanced tumor growth as reflected by increase in tumor size and weight. The LLC group with chronic T. gondii infection exhibited decreased percentages of cytotoxic CD8+ T cells and Th1 cells 25 days post-LLC injection as compared with the LLC group without T. gondii infection. At week 4 post-LLC injection, chronic T. gondii infection increased tumor formation rate [odds ratio (OR) 1.71] in both KM and BALB/c mice. CONCLUSIONS: Our research elucidates the dynamics between T. gondii infection and tumorigenesis. Tumor-induced immune suppression promoted T. gondii replication in the brain. Acute and chronic T. gondii infection had opposing effects on tumor development.

Differential transcriptome study on the damage of testicular tissues caused by chronic infection of T. gondii in mice.

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that is widely distributed in humans and warm-blooded animals. T. gondii chronic infections can cause toxoplasmic encephalopathy, adverse pregnancy, and male reproductive disorders. In male reproduction, the main function of the testis is to provide a stable place for spermatogenesis and immunological protection. The disorders affecting testis tissue encompass abnormalities in the germ cell cycle, spermatogenic retardation, or complete cessation of sperm development. However, the mechanisms of interaction between T. gondii and the reproductive system is unclear. The aims were to study the expression levels of genes related to spermatogenesis, following T. gondii infection, in mouse testicular tissue. METHODS: RNA-seq sequencing was carried out on mouse testicular tissues from mice infected or uninfected with the T. gondii type II Prugniaud (PRU) strain and validated in combination with real-time quantitative PCR and immunofluorescence assays. RESULTS: The results showed that there were 250 significant differentially expressed genes (DEGs) (P < 0.05, |log2fold change| â‰§ 1). Bioinformatics analysis showed that 101 DEGs were annotated to the 1696 gene ontology (GO) term. While there was a higher number of DEGs in the biological process classification as a whole, the GO enrichment revealed a significant presence of DEGs in the cellular component classification. The Arhgap18 and Syne1 genes undergo regulatory changes following T. gondii infection, and both were involved in shaping the cytoskeleton of the blood-testis barrier (BTB). The number of DEGs enriched in the MAPK signaling pathway, the ERK1/2 signaling pathway, and the JNK signaling pathway were significant. The PTGDS gene is located in the Arachidonic acid metabolism pathway, which plays an important role in the formation and maintenance of BTB in the testis. The expression of PTGDS is downregulated subsequent to T. gondii infection, potentially exerting deleterious effects on the integrity of the BTB and the spermatogenic microenvironment within the testes. CONCLUSIONS: Overall, our research provides in-depth insights into how chronic T. gondii infection might affect testicular tissue and potentially impact male fertility. These findings offer a new perspective on the impact of T. gondii infection on the male reproductive system.

4D label-free proteomic analysis reveals key potential pathways of Toxoplasma invasion into the central nervous system.

Toxoplasma gondii is a successful parasite capable of infecting a wide range of warm-blooded animals, including people, livestock, and wildlife. In individuals with intact immune function, T. gondii can invade the host brain tissue by altering the blood-brain barrier permeability, leading to chronic infection. Proteins play crucial regulatory roles in disease progression. By monitoring changes in proteins, a deeper understanding of the molecular mechanisms underlying host resistance to infection and the potential pathogenic mechanisms of pathogens can be gained. This study analyzed differential protein expression and associated signaling pathways in mouse brain tissues during acute and chronic T. gondii infection using proteomic and bioinformatics methods. The results showed that during acute and chronic T. gondii infection stages, 74 and 498 differentially expressed proteins (DEPs) were identified in mouse brain tissue, respectively. Among them, 45 and 309 were up-regulated, while 29 and 189 were down-regulated. GO and KEGG analyses revealed that some of these DEPs were implicated in host immunity, pathogen immune evasion, and T. gondii invasion of the central nervous system, particularly interleukin production and secretion, complement system activation, and alterations in tight junction pathways. Notably, the upregulation of Rab13 was identified as a potential molecular mechanism for T. gondii to regulate blood-brain barrier permeability and facilitate central nervous system invasion. Our findings provided fundamental data for understanding host control of Toxoplasmosis infection and offered new insights into parasite immune evasion and invasion mechanisms within the central nervous system. These insights are crucial for developing strategies to prevent the establishment of chronic T. gondii infection.

Berberine modulates the immunometabolism and differentiation of CD4+ T cells alleviating experimental arthritis by suppression of M1-exo-miR155.

BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.

The interactive effects of family violence and peer support on adolescent depressive symptoms: The mediating role of cognitive vulnerabilities.

BACKGROUND: Family violence as an inducing factor of depressive symptoms has been confirmed in previous studies. However, the mechanisms underlying this association are not well understood, particularly in Chinese adolescents. Guided by the social-ecological diathesis-stress model, this three-wave longitudinal study aimed to examine the effects of an individual's cognitive vulnerabilities (rejection-sensitivity anxiety and negative cognitive error) and positive societal contexts (peer support) on the link between family violence and depressive symptoms in Chinese society. METHODS: A total of 859 Chinese adolescents (44.35 % female; Mage = 12.73, SD = 0.43 at baseline) completed self-reporting surveys that assessed variables associated with study and peer-nominated peer support. RESULTS: The results showed that family violence increased the incidence of depressive symptoms in adolescents after two years, resulting in rejection-sensitivity anxiety and negative cognitive error. Surprisingly, higher self-reported peer support, although not peer-nominated support, exacerbated rather than mitigated this indirect effect, supporting the reverse stress-buffering model and extending the healthy context paradox. LIMITATIONS: Most of the measures were based on participants' self-reports. CONCLUSIONS: These results emphasize the importance of individual cognition and societal contexts in adolescents with traumatic experiences and provide empirical evidence for the intervention and clinical treatment of depressive symptoms.

Fluorinated carboxymethyl chitosan-based nano-prodrugs for precisely synergistic chemotherapy.

The clinical transformation of polysaccharide-based nano-prodrugs remains a long way off, due to the shackles on easy metabolic clearance, dilemma of dose-dependent toxicity and immunogenicity, and poor tumor selectivity. To address these challenges, the fluorinated dual-crosslinked carboxymethyl chitosan (CMCS)-based nano-prodrugs with precise structure were facilely developed through the reaction of CMCS with water-soluble stimuli-responsive synergistic small molecule prodrug (Pt(IV)-1), glutaraldehyde and heptafluorobutyric anhydride successively. The fluorination enabled the nano-prodrugs to display metabolic stability and improve tumoral cellular uptake. The pH/glutathione (GSH)-sensitive dual-crosslinked structure enabled the nano-prodrugs to show physicochemical stability at physiological pH, selective drug release and synergistic cytotoxicity at tumoral intracellular pH/GSH, and circumventing the dilemma of dose-dependent toxicity and immunogenicity induced by that crosslinked or grafted via a single drug. These superior performances promoted stability in long-term storage and circulation, normal blood routine and aminotransferase, fantastic hemocompatibility, selective tumor accumulation and precisely synergistic chemotherapy, therefore achieving significant tumor growth inhibition while minimizing side effects. Thus, the precise fluorinated dual-crosslinked CMCS-based nano-prodrugs have great potential for selective clinical cancer treatment.

Hexokinase inhibitor 2-deoxyglucose coordinates citrullination of vimentin and apoptosis of fibroblast-like synoviocytes by inhibiting HK2 /mTORC1-induced autophagy.

High hexokinase 2 (HK2) expression is associated with aberrant activation of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA). However, the mechanism by which this occurs has not been fully elucidated. To investigate the role of HK2 and its underlying mechanism, adjuvant arthritis (AA) rats were treated with the HK2 inhibitor, 2-deoxyglucose (2-DG). In conjunction with HK2 knockdown experiments in FLSs, we evaluated the effect of HK2 on the citrullination of vimentin (cVIM), autophagy and apoptosis-associated protein expression, including that of cVIM, LC3, p62, Beclin1, Bax, Bcl2, and caspase 3. We further investigated the interaction of HK2 with downstream mTORC1 signaling effectors. Correlation analysis revealed that 2-DG treatment and HK2 knockdown upregulated the expression levels of caspase3, Bax, and p62 and downregulated the expression levels of LC3, Bcl2, and Beclin1, as well as decreasing vimentin citrullination. Furthermore, interactions between HK2 and mTOR decreased, coinciding with mTORC1 pathway activation. These findings suggest that the regulation of apoptosis and cVIM by HK2/mTORC1-dependent autophagy involves the inhibition of aberrant FLSs activation in the rat model of arthritis.

Insight into the current Toxoplasma gondii DNA vaccine: a review article.

INTRODUCTION: Toxoplasma gondii (T.gondii) is a widespread protozoan with significant economic losses and public health importance. But so far, the protective effect of reported DNA-based vaccines fluctuates widely, and no study has demonstrated complete protection. AREAS COVERED: This review provides an inclusive summary of T. gondii DNA vaccine antigens, adjuvants, and some other parameters. A total of 140 articles from 2000 to 2021 were collected from five databases. By contrasting the outcomes of acute and chronic challenges, we aimed to investigate and identify viable immunological strategies for optimum protection. Furthermore, we evaluated and discussed the impact of several parameters on challenge outcomes in the hopes of developing some recommendations to assist better future horizontal comparisons among research. EXPERT OPINION: In the coming five years of research, the exploration of vaccine cocktails combining invasion antigens and metabolic antigens with genetic adjuvants or novel DNA delivery methods may offer us desirable protection against this multiple stage of life parasite. In addition to finding a better immune strategy, developing better in silico prediction methods, solving problems posed by variables in practical applications, and gaining a more profound knowledge of T.gondii-host molecular interaction is also crucial towards a successful vaccine.

Berberine ameliorates collagen-induced arthritis in mice by restoring macrophage polarization via AMPK/mTORC1 pathway switching glycolytic reprogramming.

Dysfunction of macrophage polarization majorly contributes to the progression of rheumatoid arthritis (RA). Polarization and functions of activated macrophages are closely associated with the reprogramming of intracellular metabolisms. Previously, we demonstrated that the anti-arthritis effect of berberine (BBR) in rats with adjuvant-induced arthritis (AA) may be related to AMP-activated protein kinase (AMPK) activation (a key regulator in the biological energy metabolism), and balanced macrophage polarization. However, the specific molecular mechanism of BBR in macrophage metabolism is yet to be elucidated. In this study, we clarified that BBR ameliorated articular inflammation and restored M1/M2 ratio in collagen-induced arthritis (CIA) mice in an AMPK-dependent manner. Mechanistically, BBR reversed the effects of mTORC1 agonist leucine (Leu) on regulating macrophage polarization through activation of AMPK to switch glycolytic reprogramming. Furthermore, BBR inhibition of mTORC1 rely on activation of AMPK to phosphorylate raptor and TSC2 instead of destroying its structure. Our study revealed that the activation of AMPK is required for the BBR-mediated anti-arthritis effect by downregulating mTORC1/HIF-1α and inhibiting the glycolysis in M1 macrophages.

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model.

BACKGROUND: In order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery. METHODS: We retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018-December 2020). The validation set included separate data points (n = 225, January 2018-December 2020). RESULTS: In this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAFV600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively. CONCLUSION: A simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.

Dynamic crosslinked polymeric nano-prodrugs for highly selective synergistic chemotherapy.

To achieve highly selective synergistic chemotherapy attractive for clinical translation, the precise polymeric nano-prodrugs (PPD-NPs) were successfully constructed via the facile crosslinking reaction between pH-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug (Pt(IV)-1). PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin (DMC). Moreover, PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure, suitable negative potentials and low critical micelle concentration (CMC), improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular pH, promoted efficient disintegration and drug release at tumoural intracellular pH/glutathione, and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2, achieving significant tumour suppression while decreasing the side effects. Thus, the dynamic crosslinked polymeric nano-prodrugs exhibit tremendous potential for clinically targeted synergistic cancer therapy.

PROTEOMIC ANALYSIS OF TAENIA SOLIUM CYST FLUID BY SHOTGUN LC-MS/MS.

Taenia solium cysts were collected from pig skeletal muscle and analyzed via a shotgun proteomic approach to identify known proteins in the cyst fluid and to explore host-parasite interactions. Cyst fluid was aseptically collected and analyzed with shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene alignment and annotation were performed using Blast2GO software followed by gene ontology analysis of the annotated proteins. The pathways were further analyzed with the Kyoto Encyclopedia of Genes and Genomes (KEGG), and a protein-protein interaction (PPI) network map was generated using STRING software. A total of 158 known proteins were identified, most of which were low-molecular-mass proteins. These proteins were mainly involved in cellular and metabolic processes, and their molecular functions were predominantly related to catalytic activity and binding functions. The pathway enrichment analysis revealed that the known proteins were mainly enriched in the PI3K-Akt and glycolysis/gluconeogenesis signaling pathways. The nodes in the PPI network mainly consisted of enzymes involved in sugar metabolism. The cyst fluid proteins screened in this study may play important roles in the interaction between the cysticerci and the host. The shotgun LC-MS/MS, gene ontology, KEGG, and PPI network map data will be used to identify and analyze the cyst fluid proteome of cysticerci, which will provide a basis for further exploration of the invasion and activities of T. solium.

The glycolysis inhibitor 2-deoxyglucose ameliorates adjuvant-induced arthritis by regulating macrophage polarization in an AMPK-dependent manner.

Macrophages are highly plastic cells critical for the development of rheumatoid arthritis (RA). Macrophages exhibit a high degree of pro-inflammatory plasticity in RA, accompanied by a metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis. 2-deoxyglucose (2-DG), a glycolysis inhibitor, has previously been shown to exhibit anti-inflammatory and anti-arthritic properties. However, the specific mechanisms of inflammatory modulation by 2-DG remain unclear. This study used 2-DG to treat rats with adjuvant arthritis (AA) and investigated its specific anti-arthritic mechanisms in the murine-derived macrophage cell line RAW264.7 in vitro. 2-DG reduced the arthritis index as well as alleviated cellular infiltration, synovial hyperplasia, and bone erosion in AA rats. Moreover, 2-DG treatment modulated peritoneal macrophage polarization, increasing levels of the arginase1 (Arg1) and decreasing expression of the inducible nitric oxide synthase (iNOS). 2-DG activated AMP-activated protein kinase (AMPK) via phosphorylation and reduced activation of the nuclear factor κB (NF-κB) in peritoneal macrophages of AA rats. In vitro, we verified that 2-DG promoted macrophage transition from M1 to M2-type by upregulating the expression of p-AMPKα and suppressing NF-κB activation in LPS-stimulated RAW264.7 cells. LPS-induced macrophages exhibited a metabolic shift from glycolysis to OXPHOS following 2-DG treatment, as observed by reduced extracellular acidification rate (ECAR), lactate export, glucose consumption, as well as an elevated oxygen consumption rate (OCR) and intracellular ATP concentration. Importantly, changes in polarization and metabolism in response to 2-DG were dampened after AMPKα knockdown. These findings indicate that the anti-arthritic 2-DG effect is mediated by a modulation of macrophage polarization in an AMPK-dependent manner.

Anti-arthritis effect of berberine associated with regulating energy metabolism of macrophages through AMPK/ HIF-1α pathway.

Berberine (BBR) is the effective constituent of Cortex phellodendri and was characterized as an excellent anti-microbial agent with significant anti-inflammatory effects. Previously, we had demonstrated that BBR alleviated the inflammatory response in adjuvant-induced arthritis (AA) rats by regulating polarization of macrophages. However, the exact mechanics by which BBR regulates macrophage polarization remained unclear. Here, we showed that BBR treatment had little influence on total number of macrophages in joints of AA rats, but increased the proportion of M2 macrophages and decreased the proportion of M1 macrophages. Meanwhile, we found BBR up-regulated the expression of AMP-activated protein kinase phosphorylation (p-AMPK) and down-regulated the expression of Hypoxia inducible factor 1α (HIF-1α) in synovial macrophages of AA rats. In vitro, using LPS-stimulated peritoneal macrophages from normal rats, we also verified that pretreatment with BBR promoted transition from M1 to M2 by up-regulating the expression of p-AMPK and suppressing the expression of HIF-1α. Compound C (an AMPK inhibitor) could abrogate the inhibition of BBR on migration of macrophages. Glycolysis of M1 suppressed by BBR through decreasing lactate export, glucose consumption, and increasing intracellular ATP content, which was remarkably reversed by Compound C. These findings indicated that anti-arthritis effect of BBR is associated with regulating energy metabolism of macrophages through AMPK/HIF-1α pathway.

The Relationship Between Sensation Seeking and Tobacco and Alcohol Use Among Junior High School Students: The Regulatory Effect of Parental Psychological Control.

The present study primarily aims to examine differences in the use of tobacco and alcohol by junior high school students under different parental control levels (including parental psychological control and parental behavioral control). It thus explores the regulatory effect of parental control on the relationship between adolescent sensation seeking and tobacco and alcohol use. A total of 1,050 junior high school students in Shandong province were surveyed using sensation-seeking scale, parental control scale, and adolescent health-related risk behavior questionnaire. As the results showed, (1) sensation seeking and gender had effects on the use of tobacco and alcohol among junior high school students; (2) parental psychological control can enhance and moderate the relationship between sensation seeking and the use of tobacco and alcohol; (3) parental behavioral control cannot regulate the relationship between sensation seeking and the use of tobacco and alcohol among junior high school students; and (4) no significant urban-rural differences were found regarding the regulatory effects of parental psychological control on sensation seeking and alcohol and tobacco use in junior high school students.