The emerging role of extracellular vesicles in the diagnosis and treatment of autism spectrum disorders.

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by restricted, repetitive behavioral patterns and deficits in social interactions. The prevalence of ASD has continued to rise in recent years. However, the etiology and pathophysiology of ASD remain largely unknown. Currently, the diagnosis of ASD relies on behavior measures, and there is a lack of reliable and objective biomarkers. In addition, there are still no effective pharmacologic therapies for the core symptoms of ASD. Extracellular vesicles (EVs) are lipid bilayer nanovesicles secreted by almost all types of cells. EVs play a vital role in cell-cell communications and are known to bear various biological functions. Emerging evidence demonstrated that EVs are involved in many physiological and pathological processes throughout the body and the content in EVs can reflect the status of the originating cells. EVs have demonstrated the potential of broad applications for the diagnosis and treatment of various brain diseases, suggesting that EVs may have also played a role in the pathological process of ASD. Besides, EVs can be utilized as therapeutic agents for their endogenous substances and biological functions. Additionally, EVs can serve as drug delivery tools as nano-sized vesicles with inherent targeting ability. Here, we discuss the potential of EVs to be considered as promising diagnostic biomarkers and their potential therapeutic applications for ASD.

Study of the relationship between pressure and sensitivity of energetic materials based on first-principles calculation.

CONTEXT: In order to study the relationship between the sensitivity and pressure of energetic materials, six kinds of energetic materials were selected as the research object. The crystal structure, electronic, and phonon properties under hydrostatic pressure of 0 ~ 45 GPa were calculated by first principles. The calculation results show that the lattice parameters and band gap values of these six energetic materials decrease with the increase of pressure. The peak of the density of states decreases and moves to the low energy direction, and the electrons become more active. Meanwhile, the effect of pressure on the sensitivity of the energetic materials is analyzed based on the multi-phonon up-pumping theory. The number of doorway modes and integral of projected phonon density of states under high pressure is calculated. The results show that both of them increase with the increase of pressure. And the smaller the value of the band gap, the larger the number of doorway modes and integral of projected phonon density of states, and the more sensitive the energetic material is. METHODS: All calculations are performed using the Materials Studio software based on density functional theory. The Perdew-Burke-Ernzerhof (PBE) functional of the generalized gradient approximation (GGA) is used to calculate the exchange correlation function, and the Grimme dispersion correction method is used to deal with the weak intermolecular interaction. The structure of the compound was optimized by BFGS algorithm. The linear response is used to calculate the phonon properties of energetic materials. The plane wave cutoff energy was set to 830 eV. The K-point grids of TATB, FOX-7, TNX, RDX, TNT, and HMX were chosen as 2 × 2 × 2, 2 × 2 × 1, 2 × 1 × 1, 1 × 1 × 1, 1 × 2 × 1, and 2 × 1 × 2.

Desulfurative Functionalization of ß-Acyl Allylic Sulfides with N-H Free Indoles Highly Regioselective at C3 and N1 Positions: Rapid Access to α-Branched Enones.

A regiodivergent allylation of 1H-indoles highly selectively at the C3 and N1 positions with ß-acyl allylic sulfides through desulfurative C-C/C-N bond-forming reactions has been developed under mild conditions. Notably, the remarkable site-selective switch can be achieved by a delicate choice of solvents and bases. This cost-efficient method displays a broad substrate scope, good functional compatibility, and excellent site-selectivity, thus offering a divergent synthesis of indole substituted α-branched enones, which possess diverse potential opportunities for further applications and derivatization.

Garbractin A, a Polycyclic Polyprenylated Acylphloroglucinol with a 4,11-dioxatricyclo[4.4.2.01,5]Dodecane Skeleton from Garcinia bracteata Fruits.

Garbractin A (1), a structurally complicated polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented 4,11-dioxatricyclo[4.4.2.01,5] dodecane skeleton, was isolated from the fruits of Garcinia bracteata, along with five new biosynthetic analogues named garcibracteatones A-E (2-6). Their structures containing absolute configurations were revealed using spectroscopic data, the residual dipolar coupling-enhanced NMR approach, and quantum chemical calculations. The antihyperglycemic effect of these PPAPs (1-6) was evaluated using insulin-resistant HepG2 cells (IR-HepG2 cells) induced through palmitic acid (PA). Compounds 1, 3, and 4 were found to significantly promote glucose consumption in the IR-HepG2 cells and, therefore, may hold potential as candidates for treating hyperglycemia.

Daily Effects of COVID-19 News on Personal Protective Behaviors Through COVID-19 Anxiety: The Significance of Direct Wuhan Epidemic Experience.

BACKGROUND: Drawing on cognitive appraisal theory, this study investigates the effect of daily COVID-19 news on daily anxiety and protective behaviors (e.g., wearing masks and washing hands). This study proposes that such processes, leading to self-protection, are highly likely when individuals have directly experienced the Wuhan epidemic at the beginning of 2020, which is the most serious COVID-19 outbreak in history. METHODS: The positive effect of daily COVID-19 news on daily protective behaviors through daily COVID-19 anxiety was examined in this study, which was hypothesized to be accentuated by direct Wuhan epidemic experience. An online survey based on the experience sample method (ESM) was conducted during the COVID-19 epidemic in Hebei Province, China, at the beginning of 2021, in which 82 working adults participated in a daily survey for five consecutive days. Once a day during the five-day period, the participants reported their daily COVID-19 news exposure, daily COVID-19 anxiety, and daily protective behaviors. Wuhan epidemic experience was measured by the place of residence of the participants during the 2020 Wuhan epidemic through a separate general survey conducted before the ESM survey. RESULTS: Analysis of 392 day-level data confirmed the positive link between daily COVID-19 news and daily protective behaviors, mediated by daily COVID-19 anxiety (b = 0.03, SE = 0.01, p = 0.018). Furthermore, the mediated effect was significant for the participants with direct COVID-19 experience in Wuhan in 2020 (b = 0.05, SE = 0.03, p = 0.041) but not significant for those without direct experience in Wuhan (b = 0.01, SE = 0.01, p = 0.461). Thus, the results confirmed the positive moderating role of Wuhan epidemic experience. CONCLUSIONS: The analysis reveals the psychological mechanism through which COVID-19 information promotes self-protection measures to control the infectious disease and highlights the importance of direct COVID-19 experience in generating such an effect.

The pros and cons of ubiquitination on the formation of protein condensates.

Ubiquitination, a post-translational modification that attaches one or more ubiquitin (Ub) molecules to another protein, plays a crucial role in the phase-separation processes. Ubiquitination can modulate the formation of membrane-less organelles in two ways. First, a scaffold protein drives phase separation, and Ub is recruited to the condensates. Second, Ub actively phase-separates through the interactions with other proteins. Thus, the role of ubiquitination and the resulting polyUb chains ranges from bystanders to active participants in phase separation. Moreover, long polyUb chains may be the primary driving force for phase separation. We further discuss that the different roles can be determined by the lengths and linkages of polyUb chains which provide preorganized and multivalent binding platforms for other client proteins. Together, ubiquitination adds a new layer of regulation for the flow of material and information upon cellular compartmentalization of proteins.

Chlorogenic Acid Induced Neuroblastoma Cells Differentiation via the ACAT1-TPK1-PDH Pathway.

BACKGROUND: Chlorogenic acid (CHA) has been shown to have substantial biological activities, including anti-inflammatory, antioxidant, and antitumor effects. However, the pharmacological role of CHA in neuroblastoma has not yet been assessed. Neuroblastoma is a type of cancer that develops in undifferentiated sympathetic ganglion cells. This study aims to assess the antitumor activity of CHA against neuroblastoma and reveal its mechanism of action in cell differentiation. METHODS: Be(2)-M17 and SH-SY5Y neuroblastoma cells were used to confirm the differentiation phenotype. Subcutaneous and orthotopic xenograft mouse models were also used to evaluate the antitumor activity of CHA. Seahorse assays and metabolomic analyses were further performed to investigate the roles of CHA and its target ACAT1 in mitochondrial metabolism. RESULTS: CHA induced the differentiation of Be(2)-M17 and SH-SY5Y neuroblastoma cells in vivo and in vitro. The knockdown of mitochondrial ACAT1, which was inhibited by CHA, also resulted in differentiation characteristics in vivo and in vitro. A metabolomic analysis revealed that thiamine metabolism was involved in the differentiation of neuroblastoma cells. CONCLUSIONS: These results provide evidence that CHA shows good antitumor activity against neuroblastoma via the induction of differentiation, by which the ACAT1-TPK1-PDH pathway is involved. CHA is a potential drug candidate for neuroblastoma therapy.

Corrigendum to "Influence of interaction between organic cation and inorganic unit in bi-based hybrid perovskites for photoelectronic properties" < [Heliyon Volume 8, Issue 12, December 2022, Article e12528]>.

[This corrects the article DOI: 10.1016/j.heliyon.2022.e12528.].

[Pollution Characteristics and Risk Assessment of Antibiotics and Resistance Genes in Different Water Sources in the Wuhan Section of the Yangtze River].

The distribution characteristics, correlations, and potential ecological risks of 13 antibiotics and 10 antibiotic resistance genes (ARGs) in 16 water sources in Wuhan were analyzed using solid-phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) and real-time quantitative PCR technology. The distribution characteristics and correlations and potential ecological risks of antibiotics and resistance genes in this region were analyzed. The results showed that a total of nine antibiotics were detected in the 16 water source samples, and the concentration range was ND-177.36 ng·L-1. The concentration distribution presented as follows:Tributary Jushui River

Berberine Ameliorates Abnormal Lipid Metabolism via the Adenosine Monophosphate-Activated Protein Kinase/Sirtuin 1 Pathway in Alcohol-Related Liver Disease.

Alcoholic fatty liver disease (AFLD) is an early stage of alcohol-related liver disease characterized by abnormal lipid metabolism in hepatocytes. To date, to our knowledge, there have been no effective strategies for preventing or treating alcohol-related liver disease besides alcohol abstinence. Berberine (BBR) is the main bioactive ingredient extracted from traditional Chinese medicines, such as Coptis and Scutellaria, which protect liver function and relieve liver steatosis. However, the potential role of BBR in AFLD remains unclear. Therefore, this study investigated the protective effects of BBR against Gao-binge model-induced AFLD in 6- to 8-week-old C57BL/6J male mice in vivo and ethyl alcohol (EtOH)-induced alpha mouse liver 12 (AML-12) cells in vitro. The results showed that BBR (200 mg/kg) attenuated alcoholic liver injury and suppressed lipid accumulation and metabolism disorders in vivo. Consistently, BBR effectively inhibited the expression of sterol regulatory element-binding transcription factor 1C, sterol regulatory element-binding transcription factor 2, fatty acid synthase, and 3-hydroxy-3-methylglutaryl-CoenzymeA reductase in EtOH-stimulated AML-12 cells in vitro and promoted the expression of sirtuin 1 (SIRT1) in EtOH-fed mice and EtOH-treated AML-12 cells. Furthermore, SIRT1 silencing attenuated the hepatic steatosis alleviation potential of BBR treatment. Mechanistically, molecular docking revealed the binding effect of BBR and adenosine monophosphate-activated protein kinase (AMPK). The results of further studies showed that a decrease in AMPK activity was accompanied by a significant inhibition of SIRT1 expression. SIRT1 silencing attenuated the protective effect of BBR, whereas the inhibition of its expression had no apparent effect on AMPK phosphorylation, suggesting that SIRT1 acts downstream of AMPK in AFLD. Collectively, BBR ameliorated abnormal lipid metabolism and alleviated EtOH-induced liver injury via the AMPK/SIRT1 pathway in AFLD mice.

BRD4 promotes hepatic stellate cells activation and hepatic fibrosis via mediating P300/H3K27ac/PLK1 axis.

Hepatic fibrosis (HF) is a reversible wound-healing response characterized by excessive extracellular matrix (ECM) deposition and secondary to persistent chronic injury. Bromodomain protein 4 (BRD4) commonly functions as a "reader" to regulate epigenetic modifications involved in various biological and pathological events, but the mechanism of HF remains unclear. In this study, we established a CCl4-induced HF model and spontaneous recovery model in mice and found aberrant BRD4 expression, which was consistent with the results in human hepatic stellate cells (HSCs)- LX2 cells in vitro. Subsequently, we found that distriction and inhibition of BRD4 restrained TGFß-induced trans-differentiation of LX2 cells into activated, proliferative myofibroblasts and accelerated apoptosis, and BRD4 overexpression blocked MDI-induced LX2 cells inactivation and promoted the proliferation and inhibited apoptosis of inactivated cells. Additionally, adeno-associated virus serotype 8-loaded short hairpin RNA-mediated BRD4 knockdown in mice significantly attenuated CCl4-induced fibrotic responses including HSCs activation and collagen deposition. Mechanistically, BRD4 deficiency inhibited PLK1 expression in activated LX2 cells, and ChIP and Co-IP assays revealed that BRD4 regulation of PLK1 was dependent on P300-mediated acetylation modification for H3K27 on the PLK1 promoter. In conclusion, BRD4 deficiency in the liver alleviates CCl4-induced HF in mice, and BRD4 participates in the activation and reversal of HSCs through positively regulating the P300/H3K27ac/PLK1 axis, providing a potential insight for HF therapy.

Roles of lncRNAs in pancreatic ductal adenocarcinoma: Diagnosis, treatment, and the development of drug resistance.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, primarily due to its late diagnosis, high propensity to metastasis, and the development of resistance to chemo-/radiotherapy. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are intimately involved in the treatment resistance of pancreatic cancer cells via interacting with critical signaling pathways and may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. DATA SOURCES: We carried out a systematic review on lncRNAs-based research in the context of pancreatic cancer and presented an overview of the updated information regarding the molecular mechanisms underlying lncRNAs-modulated pancreatic cancer progression and drug resistance, together with their potential value in diagnosis, prognosis, and treatment of PDAC. Literature mining was performed in PubMed with the following keywords: long non-coding RNA, pancreatic ductal adenocarcinoma, pancreatic cancer up to January 2022. Publications relevant to the roles of lncRNAs in diagnosis, prognosis, drug resistance, and therapy of PDAC were collected and systematically reviewed. RESULTS: LncRNAs, such as HOTAIR, HOTTIP, and PVT1, play essential roles in regulating pancreatic cancer cell proliferation, invasion, migration, and drug resistance, thus may serve as potential diagnostic/prognostic markers or therapeutic targets in PDAC. They participate in tumorigenesis mainly by targeting miRNAs, interacting with signaling molecules, and involving in the epithelial-mesenchymal transition process. CONCLUSIONS: The functional lncRNAs play essential roles in pancreatic cancer cell proliferation, invasion, migration, and drug resistance and have potential values in diagnosis, prognostic prediction, and treatment of PDAC.

Research progress of optic disc tilt in high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

With the prevalence of myopia in Asia, the prevalence of high myopia is gradually increasing, and high myopia has undoubtedly become a public health problem in Asia and even around the globe. As a relatively common pathological change in the eyes of patients with high myopia, optic disc tilt may also become a risk factor for diseases such as glaucoma and macular degeneration, thereby increasing the risk of visual impairment. However, the mechanism of optic disc tilt in high myopia and the role of optic disc tilt in the aggravation of high myopia complications still needs to be further explored. Therefore, this article collects and organizes relevant literatures on optic disc tilt, and makes a comprehensive discussion on the mechanism of optic disc shape changing caused by high myopia and the impact on various complications, so as to provide a certain basis for clinical diagnosis and treatment of high myopia and its complications.

Passively Q-switched single crystal fiber pulsed laser at 1.05†µm with T3C2Tx as the saturable absorber.

In this paper, Ti3C2Tx MXene prepared by LiF/HCl etching method was spin-coated on glass substrate and sapphire substrate as the saturable absorber (SA), and the MXene SA is combined with Yb: LuAG single crystal fiber (SCF) for the first time to achieve a 1.05 µm passively Q-switched pulsed laser output with the average power, pulse width, and repetition frequency of 1.989 W, 149.6 ns, and 365.44 kHz, respectively, which is the highest average power ever reported for passively Q-switched SCF pulsed lasers. This work enriches the research on SCF pulsed lasers and provides a feasible approach for achieving high-power all-solid-state pulsed lasers.

Association between type 1 diabetes and neurodevelopmental disorders in children and adolescents: A systematic review and meta-analysis.

Type 1 diabetes and neurodevelopmental disorders are common chronic conditions in childhood and adolescence, and having one may lead to an increased chance of developing the other. Type 1 diabetes mellitus is mainly manifested by elevated blood glucose, while neurodevelopmental diseases are composed of a variety of diseases, which are relatively complex. The purpose of this meta-analysis was to find out the prevalence of type 1 diabetes-related neurodevelopmental disorders in children and adolescents and to explore the potential association between neurodevelopmental disorders and type 1 diabetes. PubMed, Embase and Web of science databases were searched from the inception to May 22, 2022 to identify relevant studies, Finally, 24 original studies were included in the meta-analysis. Prevalence estimates for neurodevelopmental disorders in the type 1 diabetes adolescent and their 95% confidence intervals were pooled using random effects models. The pooled estimates for autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) in the type 1 diabetes population were 1.2 and 5.3%, respectively, both of which are higher than the 2019 global prevalence of ASD and ADHD in the general population. The results of the subgroup analysis showed that the prevalence of ASD and ADHD in the T1DM population tended to increase with age. In conclusion, there may be a potential link between the occurrence of type 1 diabetes mellitus and the development of neurodevelopmental disorders in children and adolescents, but more relevant studies are needed to understand the link between the underlying pathogenesis of type 1 diabetes and neurodevelopmental disorders. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CDR42022333443].

Cerebral Small Vessel Disease: A Bibliometric Analysis.

Cerebral small vessel disease is a common neurological disease, and its incidence is increasing year by year worldwide. In recent years, research on cerebral small vessel disease has gained more and more attention. Our research aims to visualize publications to identify the hotspots and frontiers of cerebral small vessel disease research, and to provide reference and guidance for further research. Publications related to cerebral small vessel disease were searched from the Web of Science Core Collection and screened according to inclusion criteria. CiteSpace 5.8.R3 was used to evaluate and visualize results, including generating web maps and analyzing annual publications, countries, institutions, bibliographic and co-cited references, and keywords; in this article, we use CiteSpace and VOSviewer for the 2012 Cerebral small vessel disease and bibliometric analysis from January 1, 2022 to April 30, 2022. A total of 3037 papers related to cerebral small vessel disease were retrieved, and the number of published papers showed a steady upward trend. Among them, Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration, the most symbolic references in the field of cerebral small vessel disease have been cited a total of 438 times. Stroke is the most active journal (227 articles) and USA publishes up to 800 articles. Harvard Med SchUniv Edinburgh (133 papers) and Charidimou (85 papers) are the institutions and authors who have made the most contributions in this field, respectively. Among the keywords, most of them are related to the pathogenesis of cerebral small vessel disease. After 2018, gut-brain axis and cortex are the keywords with the strongest number of cited outbreaks. There is increasing evidence that cerebral small vessel disease is a research frontier and may remain a research hotspot in the future.

Large plants enhance aboveground biomass in arid natural forest and plantation along differential abiotic and biotic conditions.

Big-sized trees, species diversity, and stand density affect aboveground biomass in natural tropical and temperate forests. However, these relationships are unclear in arid natural forests and plantations. Here, we hypothesized that large plants (a latent variable of tall-stature and big-crown, which indicated the effect of big-sized trees on ecosystem function and structure) enhance aboveground biomass in both arid natural forests and plantations along the gradients of climate water availability and soil fertility. To prove it, we used structural equation modeling (SEM) to test the influences of large plants located in 20% of the sequence formed by individual size (a synthetical value calculated from tree height and crown) on aboveground biomass in natural forests and plantations while considering the direct and indirect influences of species diversity as well as climatic and soil conditions, using data from 73 natural forest and 30 plantation plots in the northwest arid region of China. The results showed that large plants, species diversity, and stand density all increased aboveground biomass. Soil fertility declined aboveground biomass in natural forest, whereas it increased biomass in plantation. Although climatic water availability had no direct impact on aboveground biomass in both forests, it indirectly controlled the change of aboveground biomass via species diversity, stand density, and large plants. Stand density negatively affects large plants in both natural forests and plantations. Species diversity positively affects large plants on plantations but not in natural forests. Large plants increased slightly with increasing climatic water availability in the natural forest but decreased in plantation, whereas soil fertility inhibited large plants in plantation only. This study highlights the extended generality of the big-sized trees hypothesis, scaling theory, and the global importance of big-sized tree in arid natural forests and plantations.

Effect on implant drills and postoperative reactions for pre-extraction interradicular implant bed preparation during the COVID-19 pandemic and beyond.

The aim of the present study was to observe the abrasion of implant drills and postoperative reactions for the preparation of the interradicular immediate implant bed during the COVID-19 pandemic and beyond. Thirty-two implant drills were included in four groups: blank, improved surgery, traditional surgery, and control. In the improved surgery group, a dental handpiece with a surgical bur was used to decoronate the first molar and create a hole in the middle of the retained root complex, followed by the pilot drilling protocol through the hole. The remaining root complex was separated using a surgical bur and then extracted. Subsequently, the implant bed was prepared. Implant drills were used in the traditional surgery group to complete the decoronation, hole creation, and implant-drilling processes. The tooth remained intact until the implant bed was prepared. The surface roughness of the pilot drill was observed and measured. Surgery time, postoperative reactions (swelling, pain, and trismus), and fear of coronavirus disease 2019 scale (FCV-19S) were measured and recorded, respectively. Statistical analysis revealed significant difference with surface roughness among blank group (0.41 ± 0.05 µm), improved surgery group (0.37 ± 0.06 µm), traditional surgery group (0.16 ± 0.06 µm), and control group (0.26 ± 0.04 µm) (P < .001). Significant differences were revealed with surgery time between improved surgery group (5.63 ± 1.77 min) and traditional surgery group (33.63 ± 2.13 min) (P < .001). Swelling, pain, and trismus (improved group: r ≥ 0.864, P ≤ .006; traditional group: r ≥ 0.741, P ≤ .035) were positively correlated with the FCV-19S. This study proved that a new pilot drill could only be used once in traditional surgery but could be used regularly in improved surgery. Improved surgery was more effective, efficient, and economical than the traditional surgery. The higher FCV-19S, the more severe swelling, pain, and trismus.

7-O-(2- (Propylamino)-2-oxoethyl) hesperetin attenuates inflammation and protects against alcoholic liver injury by NLRP12.

Alcoholic liver disease (ALD) is a liver disease caused by long-term heavy drinking. Alcoholic liver injury is a part of alcoholic liver disease. A large number of studies have shown that alcohol metabolism and endotoxin / lipopolysaccharide (LPS) and cycles can cause massive activation of macrophages, leading alcoholic liver injury. Hesperetin is a dihydro-flavonoid extracted from the fruits of Citrus in Rutaceae. It has a variety of pharmacological activities, including antibacterial, anti-inflammatory, antioxidant and so on, but recent studies have shown that hesperetin derivatives have stronger anti-inflammatory effects than hesperetin. In order to improve the anti-inflammatory activity of hesperetin, our group used ethyl-bromoacetate to replace the hydroxyl group at the 7 position of hesperetin to obtain the hesperetin derivative 7-O-(2-(Propylamino)-2-oxoethyl) hesperetin (HD-4d). In this study, we found that HD-4d had hepatoprotective and anti-inflammatory effects on alcoholic liver injury in C57BL/6J mice, and it also had noticeable anti-inflammatory effects in EtOH and LPS-induced RAW264.7 cells. Besides, we found that HD-4d can reduce the expression of inflammatory factors by up-regulating NLRP12 in vivo and in vitro. We found that the expression of NLRP12 was significantly increased in EtOH and LPS-induced RAW264.7 cells compared with the control group. Moreover, the inhibitory effect of HD-4d on inflammation weakened considerably after silencing NLRP12 in RAW264.7 cells. However, when NLRP12 was overexpressed with plasmid pEX-3-NLRP12, the effect of HD-4d on alcohol and LPS induced inflammation was remarkably increased. In addition, further studies indicated that HD-4d inhibited the activation and phosphorylation of the p65 protein by up-regulating NLRP12. In conclusion, HD-4d activated NLRP12 to reduce liver injury and inflammatory response through the NF-кB pathway.

PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis.

BACKGROUND: Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). METHODS: In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1ß and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1ß in FLS by WB. RESULT: When PLCL1 was silenced, the level of IL-6, IL-1ß and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1ß and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. CONCLUSION: Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.