Screening of active components in Astragalus mongholicus Bunge and Panax notoginseng formula for anti-fibrosis in CKD: nobiletin inhibits Lgals1/PI3K/AKT signaling to improve renal fibrosis.

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.

Emodin suppresses mast cell migration via modulating the JAK2/STAT3/JMJD3/CXCR3 signaling to prevent cystitis.

AIMS: This study aimed to determine the preventive effects of emodin on cyclophosphamide (CYP)-induced cystitis and to explore the molecular mechanism. METHODS: In vivo, mice were modeled by CYP. Before a half hour of CYP treatment, Jumonji domain-containing protein-3 (JMJD3) inhibitors (GSK-J4) and emodin were used to treat CYP model mice. Bladder samples were stained for hematoxylin-eosin and toluidine blue. Next, JMJD3 was quantified by immunofluorescence staining, RT-PCR, and Western blot. CXCR3 was quantified by Western blot and ELISA. In vitro, before stimulated by lipopolysaccharide (LPS), human bladder smooth muscle cells (hBSMCs) were transfected with pcDNA3.1-JMJD3 plasmids, shRNA-JMJD3 plasmids or pretreated with emodin. Collected cells to detect JMJD3 and CXCR3 ligands again; collected supernatant of culture for Transwell assay. Finally, as the JAK2 inhibitor, AG490 was used to pretreat LPS-induced hBSMCs. Western blot was performed to quantify proteins. RESULTS: Emodin inhibited mast cell migration and suppressed the expression of JMJD3, CXCR3, and CXCR3 ligands, not only in vivo but also in vitro. The pharmacological effects of emodin were similar to GSK-J4 or JMJD3 inhibition. In addition, emodin significantly downregulated the phosphorylation of JAK2 and STAT3, and inhibited JMJD3/CXCR3 axis transduction like AG490. CONCLUSION: Emodin has a preventive effect on cystitis by inhibiting mast cell migration through inhibition of the JAK2/STAT3/JMJD3/CXCR3 signaling pathway.

Calycosin inhibited MIF-mediated inflammatory chemotaxis of macrophages to ameliorate ischemia reperfusion-induced acute kidney injury.

BACKGROUND: Inflammatory macrophage infiltration plays a critical role in acute kidney disease induced by ischemia-reperfusion (IRI-AKI). Calycosin is a natural flavone with multiple bioactivities. This study aimed to investigate the therapeutic role of calycosin in IRI-AKI and its underlying mechanism. METHODS: The renoprotective and anti-inflammatory effects of calycosin were analyzed in C57BL/6 mice with IRI-AKI and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA-seq was used for mechanism investigation. The molecular target of calycosin was screened by in silico methods and validated by surface plasmon resonance (SPR). Macrophage chemotaxis was analyzed using Transwell and agarose gel spot assays. RESULTS: Calycosin treatment significantly reduced serum creatinine and urea nitrogen and attenuated tubular destruction in IRI-AKI mice. Additionally, calycosin markedly suppressed NF-κB signaling activation and the expression of inflammatory mediators IL-1ß and TNF-α in IRI-AKI kidneys and LPS-stimulated RAW 264.7 cells. Interestingly, RNA-seq revealed calycosin remarkably downregulated chemotaxis-related pathways in RAW 264.7 cells. Among the differentially expressed genes, Ccl2/MCP-1, a critical chemokine mediating macrophage inflammatory chemotaxis, was downregulated in both LPS-stimulated RAW 264.7 cells and IRI-AKI kidneys. Consistently, calycosin treatment attenuated macrophage infiltration in the IRI-AKI kidneys. Importantly, in silico target prediction, molecular docking, and SPR assay demonstrated that calycosin directly binds to macrophage migration inhibitory factor (MIF). Functionally, calycosin abrogated MIF-stimulated NF-κB signaling activation and Ccl2 expression and MIF-mediated chemotaxis in RAW 264.7 cells. CONCLUSIONS: In summary, calycosin attenuates IRI-AKI by inhibiting MIF-mediated macrophage inflammatory chemotaxis, suggesting it could be a promising therapeutic agent for the treatment of IRI-AKI.

TGF­ß/Smad signaling in chronic kidney disease: Exploring post­translational regulatory perspectives (Review).

The TGF­ß/Smad signaling pathway plays a pivotal role in the onset of glomerular and tubulointerstitial fibrosis in chronic kidney disease (CKD). The present review delves into the intricate post­translational modulation of this pathway and its implications in CKD. Specifically, the impact of the TGF­ß/Smad pathway on various biological processes was investigated, encompassing not only renal tubular epithelial cell apoptosis, inflammation, myofibroblast activation and cellular aging, but also its role in autophagy. Various post­translational modifications (PTMs), including phosphorylation and ubiquitination, play a crucial role in modulating the intensity and persistence of the TGF­ß/Smad signaling pathway. They also dictate the functionality, stability and interactions of the TGF­ß/Smad components. The present review sheds light on recent findings regarding the impact of PTMs on TGF­ß receptors and Smads within the CKD landscape. In summary, a deeper insight into the post­translational intricacies of TGF­ß/Smad signaling offers avenues for innovative therapeutic interventions to mitigate CKD progression. Ongoing research in this domain holds the potential to unveil powerful antifibrotic treatments, aiming to preserve renal integrity and function in patients with CKD.

Research on the global trends of COVID-19 associated acute kidney injury: a bibliometric analysis.

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.

Hederagenin improves renal fibrosis in diabetic nephropathy by regulating Smad3/NOX4/SLC7A11 signaling-mediated tubular cell ferroptosis.

Diabetic nephropathy (DN) is a common complication of diabetes, characterized by renal fibrosis and poor patient prognosis. Hederagenin (HDG) has shown promising improvement in chronic kidney disease (CKD) kidney fibrosis, but its mechanism in DN-induced kidney fibrosis remains unclear. In this study, a model of diabetic nephropathy (DN) in mice was induced by intraperitoneal injection of streptozocin (50 mg/kg), while in vitro, high glucose (25 mM) was used to induce HK2 cell damage, simulating tubular injury in DN kidneys. The improvement of HDG treatment intervention was evaluated by observing changes in renal function, pathological structural damage, and the expression of fibrosis-related proteins in renal tubular cells. The results demonstrate that HDG intervention alleviates renal dysfunction and pathological damage in DN mice, accompanied by reduced expression of fibrotic markers α-smooth muscle actin (α-SMA), fibronectin (FN) and Collagen-I. Mechanistically, this study found that HDG can inhibit ferroptosis and fibrosis induced by the ferroptosis inducer Erastin (1 µM) in renal tubular cells. Phosphorylation of Smad3 promotes ferroptosis in renal tubular cells. After using its specific inhibitor SIS3 (4 µM), the expression of downstream target protein NADPH oxidase 4 (NOX4) significantly decreases, while the level of glutathione peroxidase 4 (GPX4) is notably restored, mitigating ferroptosis. Smad3 overexpression attenuates the therapeutic effect of HDG on tubular cell fibrosis induced by high glucose. These results demonstrate HDG inhibits Smad3 phosphorylation, thereby reducing the expression of NOX4 and enhancing the expression of GPX4, ultimately attenuating ferroptosis induced renal fibrosis. These findings suggest that HDG offer therapeutic potential for DN renal fibrosis by targeting Smad3-mediated ferroptosis in renal tubular cells.

Mincle as a potential intervention target for the prevention of inflammation and fibrosis (Review).

Macrophage­inducible C­type lectin receptor (Mincle) is predominantly found on antigen­presenting cells. It can recognize specific ligands when stimulated by certain pathogens such as fungi and Mycobacterium tuberculosis. This recognition triggers the activation of the nuclear factor­κB pathway, leading to the production of inflammatory factors and contributing to the innate immune response of the host. Moreover, Mincle identifies lipid damage­related molecules discharged by injured cells, such as Sin3­associated protein 130, which triggers aseptic inflammation and ultimately hastens the advancement of renal damage, autoimmune disorders and malignancies by fostering tissue inflammation. Presently, research on the functioning of the Mincle receptor in different inflammatory and fibrosis­associated conditions has emerged as a popular topic. Nevertheless, there remains a lack of research on the impact of Mincle in promoting long­lasting inflammatory reactions and fibrosis. Additional investigation is required into the function of Mincle receptors in chronological inflammatory reactions and fibrosis of organ systems, including the progression from inflammation to fibrosis. Hence, the present study showed an overview of the primary roles and potential mechanism of Mincle in inflammation, fibrosis, as well as the progression of inflammation to fibrosis. The aim of the present study was to clarify the potential mechanism of Mincle in inflammation and fibrosis and to offer perspectives for the development of drugs that target Mincle.

Kaempferitrin attenuates unilateral ureteral obstruction-induced renal inflammation and fibrosis in mice by inhibiting NOX4-mediated tubular ferroptosis.

Tubular ferroptosis significantly contributes to renal inflammation and fibrosis, critical factors in chronic kidney disease (CKD). This study aims to investigate Kaempferitrin, a potent flavonoid glycoside from Bauhinia forficata leaves, renowned for its anti-inflammatory and antitumor effects, and to elucidate its potential mechanisms in mitigating inflammation and fibrosis induced by tubular ferroptosis. The study investigated Kaempferitrin's impact on tubular ferroptosis using a unilateral ureteral obstruction (UUO) model-induced renal inflammation and fibrosis. In vitro, erastin-induced ferroptosis in primary tubular epithelial cells (TECs) was utilized to further explore Kaempferitrin's effects. Additionally, NADPH oxidase 4 (NOX4) transfection in TECs and cellular thermal shift assay (CETSA) were conducted to identify Kaempferitrin's target protein. Kaempferitrin effectively improved renal function, indicated by reduced serum creatinine and blood urea nitrogen levels. In the UUO model, it significantly reduced tubular necrosis, inflammation, and fibrosis. Its renoprotective effects were linked to ferroptosis inhibition, evidenced by decreased iron, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) levels, and increased glutathione (GSH). Kaempferitrin also normalized glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11(SLC7A11) expression, critical ferroptosis mediators. In vitro, it protected TECs from ferroptosis and consistently suppressed NOX4 expression. NOX4 transfection negated Kaempferitrin's antiferroptosis effects, while CETSA confirmed Kaempferitrin-NOX4 interaction. Kaempferitrin shows promise as a nephroprotective agent by inhibiting NOX4-mediated ferroptosis in tubular cells, offering potential therapeutic value for CKD.

RfxCas13d-mediated inhibition of Circ1647 alleviates renal fibrosis via PI3K/AKT signaling pathway.

BACKGROUND: Circular RNAs (CircRNAs) have been shown to be involved in the development of chronic kidney disease (CKD). This study aimed to investigate the role of Circ1647 in renal fibrosis, which is a hallmark of CKD. METHODS: In this study, we established a unilateral ureteral obstruction (UUO) model and delivered Circ1647 RfxCas13d knockdown plasmid into renal parenchymal cells via retrograde injection through the ureter followed by electroporation. After that, the pathological changes were determined by Hematoxylin and Eosin. Meanwhile, Immunohistochemistry, qRT-PCR and Western blot were conducted to assess the degree of fibrosis. In addition, overexpressing of Circ1647 in renal tubular epithelial cells (TCMK1) was performed to investigate the underlying mechanisms of Circ1647. RESULTS: Our results displayed that electroporation-mediated knockdown of Circ1647 by RfxCas13d knockdown plasmid significantly inhibited renal fibrosis in UUO mice as evidenced by reduced expression of fibronectin and α-SMA (alpha-smooth muscle actin). Conversely, overexpression of Circ1647 in TCMK1 cells promoted the fibrosis. In terms of mechanism, Circ1647 may mediate the PI3K/AKT Signaling Pathway as demonstrated by the balance of the phosphorylation of PI3K and AKT in vivo and the aggravated phosphorylation of PI3K and AKT in vitro. These observations were corroborated by the effects of the PI3K inhibitor LY294002, which mitigated fibrosis post Circ1647 overexpression. CONCLUSION: Our study suggests that Circ1647 plays a significant role in renal fibrosis by mediating the PI3K/AKT signaling pathway. RfxCas13d-mediated inhibition of Circ1647 may serve as a therapeutic target for renal fibrosis in CKD.

A "suicide" BCG strain provides enhanced immunogenicity and robust protection against Mycobacterium tuberculosis in macaques.

Intravenous (IV) BCG delivery provides robust protection against Mycobacterium tuberculosis (Mtb) in macaques but poses safety challenges. Here, we constructed two BCG strains (BCG-TetON-DL and BCG-TetOFF-DL) in which tetracyclines regulate two phage lysin operons. Once the lysins are expressed, these strains are cleared in immunocompetent and immunocompromised mice, yet induced similar immune responses and provided similar protection against Mtb challenge as wild type BCG. Lysin induction resulted in release of intracellular BCG antigens and enhanced cytokine production by macrophages. In macaques, cessation of doxycycline administration resulted in rapid elimination of BCG-TetOFF-DL. However, IV BCG-TetOFF-DL induced increased pulmonary CD4 T cell responses compared to WT BCG and provided robust protection against Mtb challenge, with sterilizing immunity in 6 of 8 macaques, compared to 2 of 8 macaques immunized with WT BCG. Thus, a "suicide" BCG strain provides an additional measure of safety when delivered intravenously and robust protection against Mtb infection.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. METHODS: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. RESULTS: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. CONCLUSIONS: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Development of an Engineered Mycobacterium tuberculosis Strain for a Safe and Effective Tuberculosis Human Challenge Model.

Human challenge experiments could greatly accelerate the development of a tuberculosis (TB) vaccine. Human challenge for tuberculosis requires a strain that can both replicate in the host and be reliably cleared. To accomplish this, we designed Mycobacterium tuberculosis (Mtb) strains featuring up to three orthogonal kill switches, tightly regulated by exogenous tetracyclines and trimethoprim. The resultant strains displayed immunogenicity and antibiotic susceptibility similar to wild-type Mtb under permissive conditions. In the absence of supplementary exogenous compounds, the strains were rapidly killed in axenic culture, mice and nonhuman primates. Notably, the strain that contained three kill switches had an escape rate of less than 10 -10 per genome per generation and displayed no relapse in a SCID mouse model. Collectively, these findings suggest that this engineered Mtb strain could be a safe and effective candidate for a human challenge model.

Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition.

Podocyte injury plays a critical role in the progression of focal segmental glomerulosclerosis (FSGS). Here, it is reported that B-cell translocation gene 2 (Btg2) promotes Adriamycin (ADR)-induced FSGS via Smad3-dependent podocyte-mesenchymal transition. It is found that in FSGS patients and animal models, Btg2 is markedly upregulated by podocytes and correlated with progressive renal injury. Podocyte-specific deletion of Btg2 protected against the onset of proteinuria and glomerulosclerosis in ADR-treated mice along with inhibition of EMT markers such as α-SMA and vimentin while restoring epithelial marker E-cadherin. In cultured MPC5 podocytes, overexpression of Btg2 largely promoted ADR and TGF-ß1-induced EMT and fibrosis, which is further enhanced by overexpressing Btg2 but blocked by disrupting Btg2. Mechanistically, Btg2 is rapidly induced by TGF-ß1 and then bound Smad3 but not Smad2 to promote Smad3 signaling and podocyte EMT, which is again exacerbated by overexpressing Btg2 but blocked by deleting Btg2 in MPC5 podocytes. Interestingly, blockade of Smad3 signaling with a Smad3 inhibitor SIS3 is also capable of inhibiting Btg2 expression and Btg2-mediated podocyte EMT, revealing a TGF-ß/Smad3-Btg2 circuit mechanism in Btg2-mediated podocyte injury in FSGS. In conclusion, Btg2 is pathogenic in FSGS and promotes podocyte injury via a Smad3-dependent EMT pathway.

Modified Zhibai Dihuang pill alleviated urinary tract infection induced by extended-spectrum ß-lactamase Escherichia coli in rats by regulating biofilm formation.

CONTEXT: Zhibai Dihuang pill (ZD), a traditional Chinese medicine nourishes Yin and reduces internal heat, is believed to have therapeutic effects on urinary tract infections (UTIs). OBJECTIVE: To explore the effects and mechanism of modified ZD (MZD) on UTI induced by extended-spectrum ß-lactamase (ESBLs) Escherichia coli. MATERIALS AND METHODS: Thirty Sprague-Dawley rats were randomly divided into control, model (0.5 mL 1.5 × 108 CFU/mL ESBLs E. coli), MZD (20 g/kg MZD), LVFX (0.025 g/kg LVFX), and MZD + LVFX groups (20 g/kg MZD + 0.025 g/kg LVFX), n = 6. After 14 days of treatment, serum biochemical indicators, renal function indicators, bladder and renal histopathology, and urine bacterial counts in rats were determined. Additionally, the effects of MZD on ESBLs E. coli biofilm formation and related gene expression were analyzed. RESULTS: MZD significantly decreased the count of white blood cells (from 13.12 to 9.13), the proportion of neutrophils (from 43.53 to 23.18), C-reactive protein (from 13.21 to 9.71), serum creatinine (from 35.78 to 30.15), and urea nitrogen (from 12.56 to 10.15), relieved the inflammation and fibrosis of bladder and kidney tissues, and reduced the number of bacteria in urine (from 2174 to 559). In addition, MZD inhibited the formation of ESBLs E. coli biofilms (2.04-fold) and decreased the gene expressions of luxS, pfS and ompA (1.41-1.62-fold). DISCUSSION AND CONCLUSION: MZD treated ESBLs E. coli-induced UTI inhibited biofilm formation, providing a theoretical basis for the clinical application of MZD. Further study on the clinical effect of MZD may provide a novel therapy option for UTI.

Hederagenin ameliorates renal fibrosis in chronic kidney disease through blocking ISG15 regulated JAK/STAT signaling.

Interstitial fibrosis is the key pathological characteristics of chronic kidney diseases (CKD). In this study, we reported that hederagenin (HDG) can effectively improve the renal interstitial fibrosis and its mechanism. We constructed CKD animal models of ischemia reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) respectively to observe the improvement effect of HDG on CKD. The results showed that HDG can effectively improve the pathological structure of kidney and the renal fibrosis in CKD mice. Meanwhile, HDG can also significantly reduce the expression of α-SMA and FN induced by TGF-ß in Transformed C3H Mouse Kidney-1 (TCMK1) cells. Mechanistically, we performed transcriptome sequencing on UUO kidneys treated with HDG. By real time PCR screening of the sequencing results, we determined that ISG15 plays an important role in the intervention of HDG in CKD. Subsequently, we knocked-down ISG15 in TCMK1 and found that ISG15 knock-down significantly inhibited TGF-ß-induced fibrotic protein expression and JAK/STAT activation. Finally, we performed electrotransfection and used liposomes to transfect ISG15 overexpression plasmids to up-regulate ISG15 in kidney and cells, respectively. We found that ISG15 can aggravate renal tubular cell fibrosis and abolish the protection of HDG on CKD. These results indicated that HDG significantly improves renal fibrosis in CKD by inhibiting ISG15 and its downstream JAK/STAT signaling pathway, which provides a new drug and research target for the subsequent treatment of CKD.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Recent Advances in Gold(I)-Catalyzed Approaches to Three-Type Small-Molecule Scaffolds via Arylalkyne Activation.

Gold catalysts possess the advantages of water and oxygen resistance, with the possibility of catalyzing many novel chemical transformations, especially in the syntheses of small-molecule skeletons, in addition to achieving the rapid construction of multiple chemical bonds and ring systems in one step. In this feature paper, we summarize recent advances in the construction of small-molecule scaffolds, such as benzene, cyclopentene, furan, and pyran, based on gold-catalyzed cyclization of arylalkyne derivatives within the last decade. We hope that this review will serve as a useful reference for chemists to apply gold-catalyzed strategies to the syntheses of related natural products and active molecules, hopefully providing useful guidance for the exploration of additional novel gold-catalyzed approaches.

Gold(I)-Catalyzed Tandem Intramolecular Methoxylation/Double Aldol Condensation Strategy Yielding 2,2'-Spirobi[indene] Derivatives.

The syntheses of 2,2'-spirobi[indene] derivatives based on a gold(I)-catalyzed tandem strategy involving intramolecular methoxylation/double aldol condensation were achieved. Examination of the scope of this tandem reaction by using a batch of alkynone substrates disclosed that the reaction possessed a good functional group tolerance. A cationic gold(I) catalyst/protonic acid-catalyzed mechanism for this tandem reaction is proposed.

Expression of Adenosine Deaminase and NLRP3 Inflammasome in Tuberculous Peritonitis and Their Relationship with Clinical Efficacy.

Objective: Tuberculous peritonitis (TP) can cause multiple infections of surrounding organs and tissues, leading to organ failure and endangering life safety. In this research, the relationship between adenosine deaminase (ADA), NLRP3 inflammasome, and TP and its clinical significance will be deeply explored, so as to provide new directions and reliable reference opinions for future clinical diagnosis and treatment. Methods: Altogether, 59 TP patients (research group, RG) and 52 non-TP patients (control group, CG) who were admitted to our hospital from May 2014 to June 2018 were regarded as research objects. Ascites samples of RG before treatment (admission) and one month after treatment and CG before treatment were obtained, and the ADA and NLRP3 levels were tested to evaluate the clinical and prognostic significance of the two in TP. Results: Before treatment, ADA and NLRP3 in RG were higher than CG (P < 0.05), and the sensitivity and specificity of combined detection of the two in predicting TP occurrence were 89.83% and 73.08% (P < 0.05). In addition, ADA and NLRP3 in RG patients were positively correlated with the disappearance time of abdominal pain and ascites (P < 0.05) and had excellent predictive effect on the adverse reactions during treatment (P < 0.05). After treatment, both in RG patients decreased, which was inversely proportional to the clinical efficacy (P < 0.05). Prognostic follow-up manifested that ADA and NLRP3 in relapse patients were higher than those without recurrence after treatment (P < 0.05). Conclusion: The increase of ADA and NLRP3 in TP is relevant to the adverse reactions during treatment, clinical efficacy, and prognosis recurrence after treatment. It can be used as a disease marker to confirm, intervene, and evaluate TP progression promptly.