Functional roles of circular RNAs in lung injury.

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

NLRP3 regulates CIITA/MHC II axis and interferon-γ-inducible chemokines in Malassezia globosa-infected keratinocytes.

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1ß and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases.

Unusual Pressure-Induced Self-Trapped Exciton to Free Exciton Transfer in Chiral 2D Lead Bromide Perovskites.

The phenomenon of pressure-induced emission alterations related to complex excitonic dynamics in 2D lead halide perovskites (LHPs) has gained considerable attention for understanding their structure-property relationship and obtaining inaccessible luminescence under ambient conditions. However, the well-known pressure-induced emissions are limited to the formation of self-trapped excitons (STEs) due to the structural distortion under compression, which goes against the advantage of the highly pure emission of LHPs. Here, the pressure-induced detrapping from STEs to free excitons (FEs) accompanied by the dramatic transition from broadband orangish emission to narrow blue emission has been achieved in chiral 2D LHPs and R- and S-[4MeOPEA]2PbBr4, (4MeOPEA = 4-methoxy-α-methylbenzylammonium). The combined experimental and calculated results reveal that the distortion level of PbBr6 octahedra of R- and S-[4MeOPEA]2PbBr4 exhibits an unusually significant reduction as the applied pressure increases, which leads to decreased electron-phonon coupling and self-trapped energy barrier and consequently enables the detrapping of STEs to FEs. This work illustrates the dramatic exciton transfer in 2D LHPs and highlights the potential for realizing highly efficient and pure light emissions by manipulating the structural distortion via strain engineering.

Chiral Two-Dimensional Hybrid Organic-Inorganic Perovskites for Piezoelectric Ultrasound Detection.

Hybrid organic-inorganic perovskites (HOIPs) have exhibited striking application potential in piezoelectric energy harvesting and sensing due to their high piezoelectricity, light weight, and solution processability. However, to date, the application of piezoelectric HOIPs in ultrasound detection has not yet been explored. Here, we report the synthesis of a pair of chiral two-dimensional piezoelectric HOIPs, R-(4-bromo-2-butylammonium)2PbBr4 and S-(4-bromo-2-butylammonium)2PbBr4 [R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4], which show low mechanical strength and significant piezoelectric strain coefficients that are advantageous for mechanoelectrical energy conversion. Benefiting from these virtues, the R-(BrBA)2PbBr4@PBAT and S-(BrBA)2PbBr4@PBAT [PBAT = poly(butyleneadipate-co-terephthalate)] composite films show prominent underwater ultrasound detection performance with a transmission effectivity of 12.0% using a 10.0 MHz probe, comparable with that of a polyvinylidene fluoride (PVDF) device fabricated in the same conditions. Density functional theory calculations reveal that R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4 have a beneficial acoustic impedance (5.07-6.76 MRayl) compatible with that of water (1.5 MRayl), which is responsible for the facile ultrasound-induced electricity generation. These encouraging results open up new possibilities for applying piezoelectric HOIPs in underwater ultrasound detection and imaging technologies.

Toxoplasma gondii Induces Pyroptosis in Human Placental Trophoblast and Amniotic Cells by Inducing ROS Production and Activation of Cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 Inflammasome.

Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondii infection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii-infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1ß and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii-infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii-infected cells reversed these effects. Collectively, these findings show that T. gondii induces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1-mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis.

The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.

The 5-HT7 receptors in the VLO contribute to the development of morphine-induced behavioral sensitization in rats.

The 5-hydroxytryptamine 7 receptor (5-HT7R) is one of the most recently cloned serotonin receptors which have been implicated in many physiological and pathological processes including drug addiction. Behavioral sensitization is the progressive process during which re-exposure to drugs intensified the behavioral and neurochemical responses to drugs. Our previous study has demonstrated that the ventrolateral orbital cortex (VLO) is critical for morphine-induced reinforcing effect. The aim of the present study was to investigate the effect of 5-HT7Rs in the VLO on morphine-induced behavioral sensitization and their underlying molecular mechanisms. Our results showed that a single injection of morphine, followed by a low challenge dose could induce behavioral sensitization. Microinjection of the selective 5-HT7R agonist AS-19 into the VLO during the development phase significantly increased morphine-induced hyperactivity. Microinjection of the 5-HT7R antagonist SB-269970 suppressed acute morphine-induced hyperactivity and the induction of behavioral sensitization, but had no effect on the expression of behavioral sensitization. In addition, the phosphorylation of AKT (Ser 473) was increased during the expression phase of morphine-induced behavioral sensitization. Suppression of the induction phase could also block the increase of p-AKT (Ser 473). In conclusion, we demonstrated that 5-HT7Rs and p-AKT in the VLO at least partially contribute to morphine-induced behavioral sensitization.

Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats.

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.

Pressure-Tuned Multicolor Emission of 2D Lead Halide Perovskites with Ultrahigh Color Purity.

The chemical diversity and structural flexibility of lead halide perovskites (LHPs) offer tremendous opportunities to tune their optical properties through internal molecular engineering and external stimuli. Herein, we report the wide-range and ultrapure photoluminescence emissions in a family of homologous 2D LHPs, [MeOPEA]2 PbBr4-4x I4x (MeOPEA=4-methoxyphenethylammonium; x=0, 0.2, 0.425, 0.575, 1) enabled through internal chemical pressure and external hydrostatic pressure. The chemical pressure, induced by the C-H⋅⋅⋅π interactions and halogen doping/substitution strengthens the structural rigidity to give sustained narrow emissions, and regulates the emission energy, respectively. Further manipulation of physical pressure leads to wide-range emission tuning from 412 to 647 nm in a continuous and reversible manner. This work could open up new pathways for developing 2D LHP emitters with ultra-wide color gamut and high color purity which are highly useful for pressure sensing.

Plastic bending in a semiconducting coordination polymer crystal enabled by delamination.

Coordination polymers (CPs) are a class of crystalline solids that are considered brittle, due to the dominance of directional coordination bonding, which limits their utility in flexible electronics and wearable devices. Hence, engineering plasticity into functional CPs is of great importance. Here, we report plastic bending of a semiconducting CP crystal, Cu-Trz (Trz = 1,2,3-triazolate), that originates from delamination facilitated by the discrete bonding interactions along different crystallographic directions in the lattice. The coexistence of strong coordination bonds and weak supramolecular interactions, together with the unique molecular packing, are the structural features that enable the mechanical flexibility and anisotropic response. The spatially resolved analysis of short-range molecular forces reveals that the strong coordination bonds, and the adaptive C-H···π and Cu···Cu interactions, synergistically lead to the delamination of the local structures and consequently the associated mechanical bending. The proposed delamination mechanism offers a versatile tool for designing the plasticity of CPs and other molecular crystals.

Predicting the distribution of plant associations under climate change: A case study on Larix gmelinii in China.

Association is the basic unit of plant community classification. Exploring the distribution of plant associations can help improve our understanding of biodiversity conservation. Different associations depend on different habitats and studying the association level is important for ecological restoration, regional ecological protection, regulating the ecological balance, and maintaining biodiversity. However, previous studies have only focused on suitable distribution areas for species and not on the distribution of plant associations. Larix gmelinii is a sensitive and abundant species that occurs along the southern margin of the Eurasian boreal forests, and its distribution is closely related to permafrost. In this study, 420 original plots of L. gmelinii forests were investigated. We used a Maxent model and the ArcGIS software to project the potential geographical distribution of L. gmelinii associations in the future (by 2050 and 2070) according to the climate scenarios RCP 2.6, RCP 4.5, and RCP 8.5. We used the multi-classification logistic regression analysis method to obtain the response of the suitable area change for the L. gmelinii alliance and associations to climate change under different climate scenarios. Results revealed that temperature is the most crucial factor affecting the distribution of L. gmelinii forests and most of its associations under different climate scenarios. Suitable areas for each association type are shrinking by varying degrees, especially due to habitat loss at high altitudes in special terrains. Different L. gmelinii associations should have different management measures based on the site conditions, composition structure, growth, development, and renewal succession trends. Subsequent research should consider data on biological factors to obtain more accurate prediction results.

Diversity and Dynamics of Epidermal Microbes During Grape Development of Cabernet Sauvignon (Vitis vinifera L.) in the Ecological Viticulture Model in Wuhai, China.

Grapevine-related microorganisms affect the health and yield of grapes, the metabolic pathways of the fermentation process, and the regional characteristics of wine. However, the diversity of epidermal microorganisms during the development of berries under the ecological viticulture model has not been described in detail. In this study, high-throughput amplicon sequencing technology was used to perform ITS and 16S sequencing of Cabernet Sauvignon epidermal microbes at different developmental stages in the Wuhai region to investigate the succession of epidermal microbes and their response to developmental stages and vineyard weather. The results showed that the diversity of fungi and bacteria decreased during development. Epidermal microorganisms recruited members according to their developmental stages, but retained the core taxa, such as the fungi genera Alternaria, Jattaea, and Jattaea and the bacteria genera Brevundimonas, Sphingomonas, Acinetobacter, and Pseudomonas. In addition, the microbial diversity was associated with specific meteorological parameters, implying that there was a connection between the environmental conditions of the vineyard and the microbial distribution pattern such as the fungus genus Filobasidium was positively correlated with relative humidity and negatively correlated with average high temperature, average low temperature, and average ground temperature; the bacterium genus Lactobacillus was positively correlated with sunlight time, and negatively correlated with relative humidity. In conclusion, this study can help vineyard managers understand the microbial consortia associated with particular diseases, and also the dynamics of infection processes in order to take preventive actions, especially at the most critical moments.

Dangling Octahedra Enable Edge States in 2D Lead Halide Perovskites.

The structural reconstruction at the crystal layer edges of 2D lead halide perovskites (LHPs) leads to unique edge states (ES), which are manifested by prolonged carrier lifetime and reduced emission energy. These special ES can effectively enhance the optoelectronic performance of devices, but their intrinsic origin and working mechanism remain elusive. Here it is demonstrated that the ES of a family of 2D Ruddlesden-Popper LHPs [BA2 CsPb2 Br7 , BA2 MAPb2 Br7 , and BA2 MA2 Pb3 Br10 (BA = butylammonium; MA = methylammonium)] arise from the rotational symmetry elevation of the PbBr6 octahedra dangling at the crystal layer edges. These dangling octahedra give rise to localized electronic states that enable an effective transport of electrons from the interior to layer edges, and the population of electrons in both the interior states and the ES can be manipulated via controlling the external fields. Moreover, the abundant phonons, activated by the dangling octahedra, can interact with electrons to facilitate radiative recombination, counterintuitive to the suppressive role commonly observed in conventional semiconductors. This work unveils the intrinsic atomistic and electronic origins of ES in 2D LHPs, which can stimulate the exploration of ES-based exotic optoelectronic properties and the corresponding design of high-performance devices for these emergent low-dimensional semiconductors.

Multifunctional Chiral 2D Lead Halide Perovskites with Circularly Polarized Photoluminescence and Piezoelectric Energy Harvesting Properties.

Introducing the chiral spacers to two-dimensional (2D) lead halide perovskites (LHPs) enables them to exhibit circularly polarized photoluminescence (CPPL), which could have applications in chiral-optics and spintronics. Despite that a great deal of effort has been made in this field, the reported polarization degree of CPPL at ambient conditions is still very limited, and the integration of multiple functionalities also remains to be explored. Here we report the structures, CPPL, and piezoelectric energy harvesting properties of chiral 2D LHPs, [R-1-(4-bromophenyl)ethylaminium]2PbI4 (R-[BPEA]2PbI4) and [S-1-(4-bromophenyl)ethylaminium]2PbI4 (S-[BPEA]2PbI4). Our results show that these chiral perovskites are direct bandgap semiconductors and exhibit CPPL centered at ∼513 nm with a maximum degree of polarization of up to 11.0% at room temperature. In addition, the unique configurational arrangement of the chiral spacers is found to be able to reduce the interlayer π-π interactions and consequently result in strong electron-phonon coupling. Furthermore, the intrinsic chirality of both R-[BPEA]2PbI4 and S-[BPEA]2PbI4 enables them to be piezoelectric active, and their composite films can be applied to generate voltages and currents up to ∼0.6 V and ∼1.5 µA under periodic impacting with a strength of 2 N, respectively. This work not only reports a high degree of CPPL but also demonstrates piezoelectric energy harvesting behavior for realizing multifunctionalities in chiral 2D LHPs.

Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER-mitochondria crosstalk in SiHa cells.

BACKGROUND: Trichomonas vaginalis causes lesions on the cervicovaginal mucosa in women; however, its pathogenesis remains unclear. We have investigated the involvement of the endoplasmic reticulum (ER) in the induction of apoptosis by T. vaginalis and its molecular mechanisms in human cervical cancer SiHa cells. METHODS: Apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), ER stress response and Bcl-2 family protein expression were evaluated using immunocytochemistry, flow cytometry, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide dye staining and western blotting. RESULTS: Trichomonas vaginalis induced mitochondrial ROS production, apoptosis, the ER stress response and mitochondrial dysfunction, such as MMP depolarization and an imbalance in Bcl-2 family proteins, in SiHa cells in a parasite burden- and infection time-dependent manner. Pretreatment with N-acetyl cysteine (ROS scavenger) or 4-phenylbutyric acid (4-PBA; ER stress inhibitor) significantly alleviated apoptosis, mitochondrial ROS production, mitochondrial dysfunction and ER stress response in a dose-dependent manner. In addition, T. vaginalis induced the phosphorylation of apoptosis signal regulating kinase 1 (ASK1) and c-Jun N-terminal kinases (JNK) in SiHa cells, whereas 4-PBA or SP600125 (JNK inhibitor) pretreatment significantly attenuated ASK1/JNK phosphorylation, mitochondrial dysfunction, apoptosis and ER stress response in SiHa cells, in a dose-dependent manner. Furthermore, T. vaginalis excretory/secretory products also induced mitochondrial ROS production, apoptosis and the ER stress response in SiHa cells, in a time-dependent manner. CONCLUSIONS: Trichomonas vaginalis induces apoptosis through mitochondrial ROS and ER stress responses, and also promotes ER stress-mediated mitochondrial apoptosis via the IRE1/ASK1/JNK/Bcl-2 family protein pathways in SiHa cells. These data suggest that T. vaginalis-induced apoptosis is affected by ROS and ER stress response via ER-mitochondria crosstalk.

FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth.

Fas-associated factor 1 (FAF1) has gained a reputation as a member of the FAS death-inducing signalling complex. However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE-19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T. gondii-induced FAF1 downregulation. In silico analysis for the FAF1 promoter sequence showed the presence of a FOXO response element (FRE), which is a conserved binding site for FOXO1 transcription factor. In accordance with the finding, FOXO1 overexpression potentiated, whereas FOXO1 depletion inhibited intracellular FAF1 expression level. We also found that FAF1 downregulation by T. gondii is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K/AKT pathway with specific inhibitors had no effect on the level of T. gondii-induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that T. gondii can downregulate host FAF1 in PI3K/AKT/FOXO1-dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby T. gondii proliferation.

LncRNA linc00152/NF-κB feedback loop promotes fibroblast-like synovial cells inflammation in rheumatoid arthritis via regulating miR-103a/TAK1 axis and YY1 expression.

INTRODUCTION: Overexpressed inflammatory cytokines are the main factors causing rheumatoid arthritis (RA) tissue damage and pathological deterioration, and lncRNAs has found to beinvolved in some autoinflammatory diseases. METHODS: We designed this study to investigate the effect of lncRNA linc00152 on rheumatoid arthritis inflammation and explore its molecular mechanism. RESULT: We found that linc00152 was not only up-regulated in rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), but also stimulated by TNF-α/IL-1ß in adose- and time-dependent manner in RAFLS and this expression depends on the NF-κB signaling pathway. Conversely, linc00152 promoted TNF-α/IL-1ß expression in RAFLS induced by TNF-α/IL-1ß. In addition, we found that linc00152 promoted TAK1 expression by targeting inhibition of miR-103a and activated TAK1-mediated NF-κB pathway. NF-kB indirectly promotes linc00152 expression by promoting the transcription activity of YY1, and YY1 directly promotes linc00152 expression by binding the promoter of linc00152. CONCLUSION: Our data suggested that the linc00152/NF-κB feedback loop promotes RAFLS inflammation via regulating miR-103a/TAK1 axis and YY1 expression. Thus, linc00152 acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment.

Silver nanoparticles induce apoptosis via NOX4-derived mitochondrial reactive oxygen species and endoplasmic reticulum stress in colorectal cancer cells.

Aim: To investigate the anticancer mechanisms of silver nanoparticles (AgNPs) in colorectal cancer. Methods: Anticancer effects of AgNPs were determined in colorectal cancer HCT116 cells and xenograft mice using cellular and molecular methods. Results: AgNPs induced mitochondrial reactive oxygen species production, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses through NOX4 and led to HCT116 cell apoptosis. Pretreatment with DPI or 4-PBA significantly inhibited mitochondrial reactive oxygen species production, apoptosis, ER stress response, NOX4 expression and mitochondrial dysfunction in AgNP-treated HCT116 cells. AgNPs also significantly suppressed HCT116 cell-based xenograft tumor growth in nude mice by inducing apoptosis and ER stress responses. Conclusion: AgNPs exert anticancer effects against colorectal cancer via ROS- and ER stress-related mitochondrial apoptosis pathways.

Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells.

BACKGROUND: Toxoplasma gondii is a parasite that primarily infects through the oral route. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) play crucial roles in the immune responses generated during parasitic infection and also drive the inflammatory response against invading parasites. However, little is known about the regulation of NLRs and inflammasome activation in T. gondii-infected human small intestinal epithelial (FHs 74 Int) cells. METHODS: FHs 74 Int cells infected with T. gondii were subsequently evaluated for morphological changes, cytotoxicity, expression profiles of NLRs, inflammasome components, caspase-cleaved interleukins (ILs), and the mechanisms of NLRP3 and NLRP6 inflammasome activation. Immunocytochemistry, lactate dehydrogenase assay, reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR, and western blotting techniques were utilized for analysis. RESULTS: Under normal and T. gondii-infected conditions, members of the NLRs, inflammasome components and caspase-cleaved ILs were expressed in the FHs Int 74 cells, except for NLRC3, NLRP5, and NLRP9. Among the NLRs, mRNA expression of NOD2, NLRP3, NLRP6, and NAIP1 was significantly increased in T. gondii-infected cells, whereas that of NLRP2, NLRP7, and CIITA mRNAs decreased significantly in a time-dependent manner. In addition, T. gondii infection induced NLRP3, NLRP6 and NLRC4 inflammasome activation and production of IL-1ß, IL-18, and IL-33 in FHs 74 Int cells. T. gondii-induced NLRP3 inflammasome activation was strongly associated with the phosphorylation of p38 MAPK; however, JNK1/2 had a weak effect. NLRP6 inflammasome activation was not related to the MAPK pathway in FHs 74 Int cells. CONCLUSIONS: This study highlighted the expression profiles of NLRs and unraveled the underlying mechanisms of NLRP3 inflammasome activation in T. gondii-infected FHs 74 Int cells. These findings may contribute to understanding of the mucosal and innate immune responses induced by the NLRs and inflammasomes during T. gondii infection in FHs 74 Int cells.

Moxibustion for Patients with Primary Dysmenorrhea at Different Intervention Time Points: A Randomized Controlled Trial.

PURPOSE: To investigate the effectiveness of moxibustion at different times of the menstrual cycle for patients with primary dysmenorrhea (PD). PATIENTS AND METHODS: Participants were 208 patients allocated to three controlled groups: one pre-menstrual treatment group (Group A), one menstrual-onset treatment group (Group B), and one waiting-list group (Group C). Groups A and B received the same intervention of moxibustion on points SP6 and RN4 but at different times. Group C, the waiting-list group, received no treatment throughout the study. Cox Menstrual Symptom Scale (CMSS) score was the primary outcome. Secondary outcomes were visual analog scale (VAS) score of pain intensity, self-rating anxiety scale (SAS) score, and self-rating depression scale (SDS) score. CMSS and VAS scores were obtained at the baseline stage (three cycles), treatment stage (three cycles), and follow-up stage (three cycles), a total of seven evaluations. SAS and SDS scores were obtained on the day of group allocation and the first day of the follow-up stage, a total of two evaluations. RESULTS: Baseline characteristics were comparable across the three groups. Pain duration (CMSS score) was significantly higher in Group C than in the other two groups at each evaluation (P<0.001). There was also a significant difference in the improvement in pain duration between Group B and Group C (P<0.001) throughout the trial. There were no significant changes in pain severity (CMSS score) after the 3-month treatment in Group A and Group B (P>0.05). Secondary outcomes showed that pre-menstrual moxibustion (Group A) was as effective as menstrual-onset moxibustion (Group B) in relieving pain intensity (VAS score) and negative mood (SDS and SAS scores). CONCLUSION: Moxibustion appears as an effective treatment for PD. Pre-menstrual application is more effective than menstrual-onset application. TRIAL REGISTRATION CHICTRORGCN IDENTIFIER: ChiCTR-TRC-14004627.