Rheumatoid arthritis (RA) is one of the chronic systemic autoimmune diseases that cardinally affect the joints. Many people all over the world suffer from the disease. Fibroblast‐like synoviocytes ...(FLSs) play a significant role in the occurrence and development of RA. The long noncoding RNA maternally expressed gene 3 (MEG3) is an imprinted gene, which participates in various cancers as a tumor suppressor. Previous studies have shown that nucleotide oligomerization domain (NOD)‐like receptors 5 (NLRC5) plays a key role in inflammatory and autoimmune diseases. Nonetheless, we know very little about the biofunctionality of MEG3 during the development of RA. In this paper, we used complete Freund's adjuvant (CFA)‐induced rats as RA animal models. The level of MEG3 significantly reduced in CFA‐induced synovial tissues and FLSs, whereas the NLRC5 levels were increased. Enforced expression of MEG3 may be responsible for the decreased level of NLRC5 and inflammatory cytokine level. The results of methylation‐specific PCR suggested that the MEG3 gene promoter was significantly methylated in CFA‐induced synovial tissues and FLSs. More important, hypermethylation of MEG3 promoter could be inhibited by 5‐aza‐2‐deoxycytidine (5‐azadC; methylation inhibitor). Besides, the expression of NLRC5 significantly decreased followed by 5‐azadc. Furthermore, DNA methyltransferases 1 (DNMT1) increased in CFA‐induced synovial tissues and cells. These results indicated that MEG3 regulates RA by targeting NLRC5 potentially.
Maternally expressed gene 3 (MEG3) may be involved in the development of rheumatoid arthritis (RA) by affecting the proliferation of fibroblast‐like synoviocytes (FLSs), whereas nucleotide oligomerization domain (NOD)‐like receptors 5 (NLRC5) promotes proliferation of FLSs in RA. Enforced expression of MEG3 decreased NLRC5 expression. These results further verified that MEG3 regulates RA by targeting NLRC5 potentially.
Designing tailor-made metal–organic frameworks (MOFs) to synthesize target nanomaterials with extraordinary electrochemical oxygen catalytic activity is highly desirable. Here, we rationally designed ...a 2D Co-MOF Co(BDC)2(SPDP)2(DMF)(H2O) (H2BDC = 1,4-benzenedicarboxylic acid, SPDP = 4,4′-(sulfonylbis(4,1-phenylene))dipyridine, DMF = N,N-dimethylformamide) as a single-source precursor through direct carbonization to afford an N, O and S-tridoped carbon matrix encapsulated with Co9S8 nanocomposites (Co9S8@TDC). By virtue of the intrinsic activity of Co9S8 nanoparticles (NPs) as well as the heteroatom-doped carbon shell, Co9S8@TDC possessed excellent electrocatalytic activities for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) in alkaline solutions. In particular, Co9S8@TDC-900 displayed an overpotential of 330 mV (vs. RHE) at current density of 10 mA cm−2 for OER and a half-wave potential of 0.78 V (vs. RHE) for ORR with the limiting current density of 5.45 mA cm−2, rivalling the performances of RuO2 and Pt/C. As the proof of concept, Co9S8@TDC-900 was employed as a bifunctional oxygen catalyst for a rechargeable Zn–air battery, exhibiting a considerable open-circuit voltage (1.50 V) and impressive long-term charge/discharge stability (45 h at 5 mA cm−2). The straightforward strategy provides a facile method for the further exploration of non-noble metal electrochemical oxygen reaction catalysts.
Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain ...unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull‐down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1‐mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1‐activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer.
Developing efficient oxygen evolution reaction (OER) electrocatalysts such as transition metal sulfides (TMSs) is of great importance to advance renewable hydrogen fuel toward further practical ...applications. Herein, NiCoS
2
nanoparticles well decorated on double-sided N-doped reduced graphene oxide sheets (NiCoS
2
/rGO) are prepared from an Al-containing ternary NiCoAl-layered double hydroxide precursor (NiCoAl-LDH) grown on GO support as an OER electrocatalyst. The Al-confinement-assisted sulfurization, followed by selective acid treatment, endows the resulting NiCoS
2
/rGO composite with the advantages: well-dispersed NiCoS
2
nanoparticles, dual-sided rGO support, as well as a large specific surface area of 119.4 m
2
·g
–1
and meso-/macroporous size distribution. The NiCoS
2
/rGO electrocatalyst exhibits an overpotential of 273 mV at 10 mA·cm
–2
and a good stability of 24 h, which outperform those of the counterparts of NiS
2
/rGO and CoS
2
/rGO. The results of electrochemical active surface area and electrochemical impedance spectra experimentally provide convincing rationales of the information of active sites and good conductivity, both underpin the enhanced electrocatalytic performances.
Graphical abstract
Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows ...potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.
With the
in situ
-generated Pb(MCP)
4
2+
(HMCP
+
= 1-methyl-4-(carboxyl)pyridinium) or M(phen)
3
2+
(M = Co, Fe and Ni; phen = 1,10-phenanthroline) complexes as structural directing agents and ...charge-balancing ions, we solvothermally synthesized and structurally characterized four new organic-inorganic hybrid iodoplumbates. Compound K
2
Pb(MCP)
4
Pb
3
I
10
(
1
) represents the first K
+
and Pb(MCP)
4
2+
co-templated hybrid haloplumbate, and exhibits a curve-like anionic layer of Pb
3
I
10
n
4
n
−
. Compounds M(phen)
3
Pb
2
I
6
·CH
3
CN (M = Co (
2
), Fe (
3
) and Ni (
4
)) have isostructural phases, and feature a one-dimensional (1D) Pb
2
I
6
n
2
n
−
anionic chain characteristic of pyramid-like PbI
5
units. The optical property studies show that compounds
1-4
exhibit semiconductor behaviors with the band gaps of 1.98-2.68 eV. In addition, the title compounds exhibited interesting photoelectrical responsive properties, with the photocurrent density in the order of
1
>
3
>
2
>
4
. The thermal stabilities of the title compounds
1-4
, as well as the theoretical band structure and density of states (DOS) of compounds
1
and
2
have also been studied.
Presented here are the syntheses, crystal structures, and optical and photoelectric properties of four metal complexes-directed hybrid iodoplumbates.
Background
Dysregulated bile acid (BA) metabolism has been linked to steatosis, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD).
Aim
To determine whether circulating BA levels ...accurately stage liver fibrosis in NAFLD.
Methods
We recruited 550 Chinese adults with biopsy‐proven NAFLD and varying levels of fibrosis. Ultra‐performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.
Results
Compared to those without fibrosis, patients with mild fibrosis (stage F1) had significantly higher levels of secondary BAs, and increased diastolic blood pressure (DBP), alanine aminotransferase (ALT), body mass index, and waist circumstance (WC). The combination of serum BAs with WC, DBP, ALT, or Homeostatic Model Assessment for Insulin Resistance performed well in identifying mild fibrosis, in men and women, and in those with/without obesity, with AUROCs 0.80, 0.88, 0.75 and 0.78 in the training set (n = 385), and 0.69, 0.80, 0.61 and 0.69 in the testing set (n = 165), respectively. In comparison, the combination of BAs and clinical/biochemical biomarkers performed less well in identifying significant fibrosis (F2‐4). In women and in non‐obese subjects, AUROCs were 0.75 and 0.71 in the training set, 0.65 and 0.66 in the validation set, respectively. However, these AUROCs were higher than those observed for the fibrosis‐4 index, NAFLD fibrosis score, and Hepamet fibrosis score.
Conclusions
Secondary BA levels were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum BAs and clinical/biochemical biomarkers for identifying mild fibrosis merits further assessment.
Secondary bile acids were significantly increased in NAFLD, especially in those with mild fibrosis. The combination of serum bile acids and clinical/biochemical biomarkers for identifying mild fibrosis is worthy of further assessment.
Neutrophils are considered as core immune cells involve in the early stage of rheumatoid arthritis (RA) and participate in the disease progression. The underlining mechanisms include the elevated ...chemotaxis and infiltration of neutrophils, the increase in the reactive oxygen species and the promotion of neutrophil extracellular traps formation. Accumulating studies demonstrated the important role of nutrients intake played in the initiation and progression of RA. This study summarized the effects of several macronutrients and micronutrients on regulating RA through the modulation of activated neutrophils and appealed for a healthy diet in RA-risk individuals as well as RA patients.
SOX family transcription factor has emerged as a double-edged sword relating to tumorigenesis and metastasis. Multiple studies have revealed different expression patterns and contradictory roles of ...SOX factors in the tumor initiation and progression. The aberrant expression of SOX factors is regulated by copy number alteration, methylation modulation, microRNAs, transcription factors and post-translational modification. This review summarizes the role of SOX factors in molecular interactions and signaling pathways during different steps of carcinogenesis, such as CSCs stemness maintenance, EMT occurrence, cell invasion, cell proliferation and apoptosis. The Wnt signaling pathway is also shown to provide vital intermediate signaling transduction. We believe that SOX family proteins may be used as prognostic markers for human clinical therapy, and novel therapy strategies targeting SOX factors should be explored in future clinical applications.
Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it ...is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stress (ELS). Weaning, as we all know, is a vital procedure that all mammalian newborns, including humans, must go through. Maternal separation (MS) stress in infancy (regarded as weaning stress in animal science) is a commonly used ELS paradigm. Drinking silicon-rich alkaline mineral water (AMW) has a therapeutic effect on enteric disease, but the specific mechanisms involved have not been reported. Herein, we discover the molecular mechanism by which silicon-rich AMW repairs ELS-induced IEI by maintaining intestinal stem cell (ISC) proliferation and differentiation through the glucagon-like peptide (GLP)2–Wnt1 axis. Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/β-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5
+
ISC cell cycle passage through the G1–S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP2
3−33
) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2–Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2–Wnt1 axis in piglets under ELS. Our research contributes to understanding the mechanism of silicon-rich AMW promoting gut epithelial regeneration and provides a new strategy for the alleviation of ELS-induced IEI.
