Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress.

Apigenin (API) is a natural flavonoid compound with antioxidant, anti fibrotic, anti-inflammatory and other effects, but there is limited research on the effect of API on liver fibrosis. This study aims to explore the effect and potential mechanism of API on liver fibrosis induced by CCl4 in mice. The results indicate that API reduces oxidative stress levels, inhibits hepatic stellate cell (HSC) activation, and exerts anti liver fibrosis effects by regulating the PKM2-HIF-1α pathway. We observed that API alleviated liver tissue pathological damage and collagen deposition in CCl4 induced mouse liver fibrosis model, promoting the recovery of liver function in mice with liver fibrosis. In addition, the API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer formation by regulating the EGFR-MEK1/2-ERK1/2 pathway, thereby preventing dimer from entering the nucleus and blocking PKM2-HIF-1α access. This change leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of liver fibrosis mice. At the same time, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis, inhibited the activation of HSC, and reduced collagen deposition. These results indicate that API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress, laying an important foundation for the development and clinical application of API as a novel drug for treating liver fibrosis.

Root rot destabilizes the Sanqi rhizosphere core fungal microbiome by reducing the negative connectivity of beneficial microbes.

The stability of microbial communities, especially among core taxa, is essential for supporting plant health. However, the impacts of disease infection on the stability of rhizosphere fungal core microbiome remain largely unexplored. In this study, we delved into the effects of root rot infestation on the community structure, function, network complexity, and stability of Sanqi fungal core microbiomes, employing amplicon sequencing combined with co-occurrence network and cohesion analyses. Our investigation revealed that root rot disease led to a decrease in the α-diversity but an increase in the ß-diversity of the Sanqi fungal core microbiomes in the rhizosphere. Notably, Ilyonectria, Plectosphaerella, and Fusarium emerged as indicator species in the rhizosphere core microbiome of root rot-infected Sanqi plants, while Mortierella predominated as the dominant biomarker taxa in healthy soils. Additionally, root rot diminished the complexity and modularity of the rhizosphere networks by reducing the metrics associated with nodes, edges, degrees, and modularity. Furthermore, root rot resulted in a reduction in the proportion of negative connections in the network and the negative/positive cohesion of the entire core fungal microbiome. Particularly noteworthy was the observation that root rot infection destabilized the rhizosphere core fungal microbiome by weakening the negative connectivity associated with beneficial agents. Collectively, these results highlight the significance of the negative connectivity of beneficial agents in ensuring the stability of core microbial community.IMPORTANCERoot rot disease has been reported as the most devastating disease in the production process of artificial cultivated Sanqi ginseng, which seriously threatens the Sanqi industry. This study provides valuable insights into how root rot influences microbial relationships within the community. These findings open up opportunities for disease prevention and the promotion of plant health by regulating microbial interactions. In summary, the research sheds light on the ecological consequences of root rot on rhizosphere fungal microbiomes and offers potential strategies for managing soil-borne diseases and enhancing plant health.

FPR1: A critical gatekeeper of the heart and brain.

G protein-coupled receptors (GPCRs) are currently the most widely focused drug targets in the clinic, exerting their biological functions by binding to chemicals and activating a series of intracellular signaling pathways. Formyl-peptide receptor 1 (FPR1) has a typical seven-transmembrane structure of GPCRs and can be stimulated by a large number of endogenous or exogenous ligands with different chemical properties, the first of which was identified as formyl-methionine-leucyl-phenylalanine (fMLF). Through receptor-ligand interactions, FPR1 is involved in inflammatory response, immune cell recruitment, and cellular signaling regulation in key cell types, including neutrophils, neural stem cells (NSCs), and microglia. This review outlines the critical roles of FPR1 in a variety of heart and brain diseases, including myocardial infarction (MI), ischemia/reperfusion (I/R) injury, neurodegenerative diseases, and neurological tumors, with particular emphasis on the milestones of FPR1 agonists and antagonists. Therefore, an in-depth study of FPR1 contributes to the research of innovative biomarkers, therapeutic targets for heart and brain diseases, and clinical applications.

Quercetin and Kaempferol inhibit HMC-1 activation via SOCE/NFATc2 signaling and suppress hippocampal mast cell activation in lipopolysaccharide-induced depressive mice.

OBJECTIVE AND DESIGN: Mast cells (MCs), as the fastest immune responders, play a critical role in the progression of neuroinflammation-related diseases, especially in depression. Quercetin (Que) and kaempferol (Kae), as two major diet-derived flavonoids, inhibit MC activation and exhibit significant antidepressant effect due to their anti-inflammatory capacity. The study aimed to explore the mechanisms of inhibitory effect of Que and Kae on MC activation, and whether Que and Kae suppress hippocampal mast cell activation in LPS-induced depressive mice. SUBJECTS AND TREATMENT: In vitro assays, human mast cells (HMC-1) were pretreated with Que or Kae for 1 h, then stimulated by phorbol 12-myristate 13-acetate (PMA) and 2,5-di-t-butyl-1,4-benzohydroquinone (tBHQ) for 3 h or 12 h. In vivo assays, Que or Kae was administered by oral gavage once daily for 14 days and then lipopolysaccharide (LPS) intraperitoneally injection to induce depressive behaviors. METHODS: The secretion and expression of TNF-α were determined by ELISA and Western blotting. The nuclear factor of activated T cells (NFAT) transcriptional activity was measured in HMC-1 stably expressing NFAT luciferase reporter gene. Nuclear translocation of NFATc2 was detected by nuclear protein extraction and also was fluorescently detected in HMC-1 stably expressing eGFP-NFATc2. We used Ca2+ imaging to evaluate changes of store-operated calcium entry (SOCE) in HMC-1 stably expressing fluorescent Ca2+ indicator jGCamP7s. Molecular docking was used to assess interaction between the Que or Kae and calcium release-activated calcium modulator (ORAI). The  hippocampal mast cell accumulation and activation  were detected by toluidine blue staining and immunohistochemistry with ß-tryptase. RESULTS: In vitro assays of HMC-1 activated by PtBHQ (PMA and tBHQ), Que and Kae significantly decreased expression and secretion of TNF-α. Moreover, NFAT transcriptional activity and nuclear translocation of NFATc2 were remarkably inhibited by Que and Kae. In addition, the Ca2+ influx mediated by SOCE was suppressed by Que, Kae and the YM58483 (ORAI inhibitor), respectively. Importantly, the combination of YM58483 with Que or Kae had no additive effect on the inhibition of SOCE. The molecular docking also showed that Que and Kae both exhibit high binding affinities with ORAI at the same binding site as YM58483. In vivo assays, Que and Kae significantly reversed LPS-induced depression-like behaviors in mice, and inhibited hippocampal mast cell activation  in LPS-induced depressive mice. CONCLUSIONS: Our results indicated that suppression of SOCE/NFATc2 pathway-mediated by ORAI channels may be the mechanism of inhibitory effect of Que and Kae on MC activation, and also suggested Que and Kae may exert the antidepressant effect through suppressing hippocampal mast cell activation.

Deciphering the Synergies of Reductive Soil Disinfestation Combined with Biochar and Antagonistic Microbial Inoculation in Cucumber Fusarium Wilt Suppression Through Rhizosphere Microbiota Structure.

Application of reductive soil disinfestation (RSD), biochar, and antagonistic microbes have become increasingly popular strategies in a microbiome-based approach to control soil-borne diseases. The combined effect of these remediation methods on the suppression of cucumber Fusarium wilt associated with microbiota reconstruction, however, is still unknown. In this study, we applied RSD treatment together with biochar and microbial application of Trichoderma and Bacillus spp. in Fusarium-diseased cucumbers to investigate their effects on wilt suppression, soil chemical changes, microbial abundances, and the rhizosphere communities. The results showed that initial RSD treatment followed by biochar amendment (RSD-BC) and combined applications of microbial inoculation and biochar (RSD-SQR-T37-BC) decreased nitrate concentration and raised soil pH, soil organic carbon (SOC), and ammonium in the treated soils. Under RSD, the applications of Bacillus (RSD-SQR), Trichoderma (RSD-T37), and biochar (RSD-BC) suppressed wilt incidence by 26.8%, 37.5%, and 32.5%, respectively, compared to non-RSD treatments. Moreover, RSD-SQR-T37-BC and RSD-T37 caused greater suppressiveness of Fusarium wilt and F. oxysporum by 57.0 and 33.5%, respectively. Rhizosphere beta diversity and alpha diversity revealed a difference between RSD-treated and non-RSD microbial groups. The significant increase in the abundance, richness, and diversity of bacteria, and the decrease in the abundance and diversity of fungi under RSD-induced treatments attributed to the general suppression. Identified bacterial (Bacillus, Pseudoxanthomonas, Flavobacterium, Flavisolibacter, and Arthrobacter) and fungal (Trichoderma, Chaetomium, Cladosporium, Psathyrella, and Westerdykella) genera were likely the potential antagonists of specific disease suppression for their significant increase of abundances under RSD-treated soils and high relative importance in linear models. This study infers that the RSD treatment induces potential synergies with biochar amendment and microbial applications, resulting in enhanced general-to-specific suppression mechanisms by changing the microbial community composition in the cucumber rhizosphere.

Exploring the mechanism of Chaihujia Longgu Muli decoction in the treatment of epilepsy in rats based on the RhoA/ROCK signaling pathway.

BACKGROUND: The Chinese herbal formula Chaihujia Longgu Muli Decoction (CD) has a good antiepileptic effect, but its mechanisms remain unclear. Therefore, in this study we explored the molecular mechanisms of CD against epilepsy. METHODS: Twelve-day-old SD rats were randomly divided into a normal group, model group, valproic acid group, and CD high, medium, and low groups. Except for the normal group, the other groups were given an intraperitoneal injection of pentylenetetrazol (PTZ) to establish epilepsy models, and the Racine score was applied for model judgment. After 14 consecutive days of dosing, the Morris water maze test was performed. Then, hippocampal Nissl staining and immunofluorescence staining were performed, and synaptic ultrastructure was observed by transmission electron microscopy (TEM). RhoA/ROCK signaling pathway proteins were detected. RESULTS: In PTZ model rats, the passing times were reduced, and the escape latency was prolonged in the Morris water maze test. Nissl staining showed that some hippocampal neurons swelled and ruptured, Nissl bodies in the cytoplasm were significantly reduced, and neurons were lost. Immunofluorescence detection revealed that the expression of PSD95 and SYP was significantly reduced. Electron microscopy results revealed that the number of synapses in hippocampal neurons was significantly reduced and the postsynaptic membrane length was significantly reduced. Western blot analysis showed that the RhoA/ROCK signaling pathway was activated, while SYP, SPD95, and PTEN expression was significantly decreased. After treatment with CD, neurobehavioral abnormalities and neuronal damage caused by epileptic seizures were improved. CONCLUSION: CD exerted an antiepileptic effect by inhibiting the activation of the RhoA/ROCK signaling pathway.

Melatonin Ameliorates Cisplatin-Induced Renal Tubular Epithelial Cell Damage through PPARα/FAO Regulation.

Previous studies revealed that melatonin ameliorated acute renal injury induced by cisplatin, but the mechanisms remain unclear. Peroxidase proliferative receptor α (PPARα) is considered the major regulator of fatty acid oxidation (FAO), which is an important source of energy for renal tubular epithelial cells. In this study, the aim was to investigate the role of melatonin in cisplatin-induced NRK-52E (rat renal tubular epithelial cell line) cell damage and the underlying mechanisms. We established a cisplatin-stimulated NRK-52E model in vitro. We assessed the levels of apoptotic proteins, including caspase-3, caspase-9, and B-cell lymphoma 2-associated X protein (Bax), as well as PPARα and FAO-related genes (Acadm, Acat1, Acsm2, Acsm3, PGC-1α, Pecr, Bdh2, and Echs1). Furthermore, we detected the effects of miR-21 and PPARα antagonist on the above indicators. We found that melatonin reduced the protein expression levels of caspase-3, caspase-9, and Bax, and increased the expression levels of the PPARα gene and protein and PPARα activity, as well as FAO-related genes, in NRK-52E cells. However, miR-21 mimics and PPARα antagonists partially antagonized the above effects of melatonin. Our data indicated that melatonin could alleviate cisplatin-induced cell damage through the upregulation of PPARα/FAO.

Polyethyleneimine modified activated carbon for high-efficiency adsorption of copper ion from simulated wastewater.

In this study, activated carbon (AC) was chemically activated using sodium hydroxide (NaOH), and polyethyleneimine (PEI) was grafted onto the AC using glutaraldehyde as a cross-linking agent. Then the modified AC was applied to treat water samples containing copper ions (Cu2+). Preparation of AC-NaOH@PEI. The grafted AC was characterized, demonstrating that the specific surface area of material decreased from 959.3 to 556.9 m2/g. The ζ-potential changed from -27.2 to 10.4 mV, and the presence of a distinct flocculation on the surface of the AC was observed via scanning electron microscopy. The results demonstrated that PEI was successfully grafted onto the surface of AC. Furthermore, the adsorption results indicated that the Cu2+ adsorption capacity of AC-NaOH@PEI was greatly enhanced with increasing PEI loading. The adsorption amount of Cu2+ by the grafted AC-NaOH@PEI-200 increased from 20.02 to 47.8 mg/g. In addition, the adsorption of Cu2+ by AC-NaOH@PEI was a pH dependent process. At a pH of 6, the maximum removal rate reached 93%. The adsorption process is better described by the Langmuir and quasi-second order adsorption models, signifying that the adsorption of Cu2+ on AC@PEI consists of monolayer adsorption and chemisorption. After four adsorption-desorption cycles, AC@PEI exhibited high adsorption capacity for Cu2+, indicating that it has good regeneration ability. It is a promising adsorbent material.

Adsorption of cadmium ions from simulated battery wastewater by polyethylene polyamine-modified activated carbon.

The objective of this work was to study the treatment of wastewater containing cadmium ions (Cd2+). Activated carbon (AC) was modified with potassium hydroxide (KOH) and polyethylene polyamine (PEPA). The structure and morphology of the modified AC was characterized. The effect of pH on adsorption was investigated, and the binary competitive adsorption and the reusability of the modified AC were studied. Subsequently the modified AC was used as an adsorbent for the removal of Cd2+ from wastewater. The adsorption capacity of optimized modified AC was 9.7 times that of unmodified AC. Kinetic adsorption curves were in accordance with pseudo-second-order kinetics, and the isothermal curves were in accordance with the Langmuir equation. The results indicate that the AC has potential in the treatment of the wastewater containing Cd2+ discharged from chemical plants during battery manufacturing.

Bone progeria diminished the therapeutic effects of bone marrow mesenchymal stem cells on retinal degeneration.

Senescence is closely related to the occurrence of retinal degeneration. Recent studies have shown that bone marrow mesenchymal stem cells (BMMSCs) have significant therapeutic effects on retinal degeneration, While BMMSCs suffer from functional decline in bone aging. Whether senescence affects BMMSCs therapy on retinal degeneration remains unknown. Here, we applied the previously established bone progeria animal model, the senescence-accelerated mice-prone 6 (SAMP6) strain, and surprisingly discovered that SAMP6 mice demonstrated retinal degeneration at 6 months old. Furthermore, BMMSCs derived from SAMP6 mice failed to prevent MNU-induced retinal degeneration in vivo. As expected, BMMSCs from SAMP6 mice exhibited impairment in the differentiation capacities, compared to those from the age-matched senescence-accelerated mice-resistant 1 (SAMR1) strain. Moreover, BMMSCs from SAMR1 mice counteracted MNU-induced retinal degeneration, with increased expression of the retina survival hallmark, N-myc downstream regulated gene 2 (NDRG2). Taken together, these findings reveal that bone progeria diminished the therapeutic effects of BMMSC on retinal degeneration.

Autotoxic Ginsenoside Disrupts Soil Fungal Microbiomes by Stimulating Potentially Pathogenic Microbes.

Autotoxic ginsenosides have been implicated as one of the major causes for replant failure of Sanqi ginseng (Panax notoginseng); however, the impact of autotoxic ginsenosides on the fungal microbiome, especially on soilborne fungal pathogens, remains poorly understood. In this study, we aimed to investigate the influence of the ginsenoside monomers Rg1, Rb1, and Rh1, and that of their mixture (Mix), on the composition and diversity of the soil fungal community, as well as on the abundance and growth of the soilborne pathogen Fusarium oxysporum in pure culture. The addition of autotoxic ginsenosides altered the composition of the total fungal microbiome, as well as the taxa within the shared and unique treatment-based components, but did not alter alpha diversity (α-diversity). In particular, autotoxic ginsenosides enriched potentially pathogenic taxa, such as Alternaria, Cylindrocarpon, Gibberella, Phoma, and Fusarium, and decreased the abundances of beneficial taxa such as Acremonium, Mucor, and Ochroconis Relative abundances of pathogenic taxa were significantly and negatively correlated with those of beneficial taxa. Among the pathogenic fungi, the genus Fusarium was most responsive to ginsenoside addition, with the abundance of Fusarium oxysporum consistently enhanced in the ginsenoside-treated soils. Validation tests confirmed that autotoxic ginsenosides promoted mycelial growth and conidial germination of the root rot pathogen F. oxysporum In addition, the autotoxic ginsenoside mixture exhibited synergistic effects on pathogen proliferation. Collectively, these results highlight that autotoxic ginsenosides are capable of disrupting the equilibrium of fungal microbiomes through the stimulation of potential soilborne pathogens, which presents a significant hurdle in remediating replant failure of Sanqi ginseng.IMPORTANCE Sanqi ginseng [Panax notoginseng (Burk.) F. H. Chen] is geoauthentically produced in a restricted area of southwest China, and successful replanting requires a rotation cycle of more than 15 to 30 years. The increasing demand for Sanqi ginseng and diminishing arable land resources drive farmers to employ consecutive monoculture systems. Replant failure has severely threatened the sustainable production of Sanqi ginseng and causes great economic losses annually. Worse still, the acreage and severity of replant failure are increased yearly, which may destroy the Sanqi ginseng industry in the near future. The significance of this work is to decipher the mechanism of how autotoxic ginsenosides promote the accumulation of soilborne pathogens and disrupt the equilibrium of soil fungal microbiomes. This result may help us to develop effective approaches to successfully conquer the replant failure of Sanqi ginseng.

Berberine attenuates fructose-induced insulin resistance by stimulating the hepatic LKB1/AMPK/PGC1α pathway in mice.

Context: Berberine is an alkaloid that possesses various pharmacologic effects.Objective: To explore the mechanism of berberine to improve insulin sensitivity in fructose-fed mice.Materials and methods: Sixty male ICR mice were randomly divided into 6 groups (10 mice in each group): control, fructose, pioglitazone (10 mg/kg) and berberine (50, 100, and 200 mg/kg). Except for the control group, the mice received 20% fructose drinking for 10 weeks. Pioglitazone and berberine were orally administered once daily during the last 4 weeks. The insulin sensitivity was evaluated using an oral glucose tolerance test (OGTT). The serum levels of fasting glucose and insulin, blood lipids, and hormones were determined. The hepatic AMP and ATP contents were detected using high performance liquid chromatography (HPLC) analysis, and the protein expression was examined by immunoblotting.Results: Berberine significantly reversed the insulin resistance induced by fructose, including lowering fasting insulin levels (from 113.9 to 67.4) and area under the curve (AUC) during OGTT (from 1310 to 1073), decreasing serum leptin (from 0.28 to 0.13) and increasing serum adiponectin levels (from 1.50 to 2.80). Moreover, berberine enhanced the phosphorylation levels of protein kinase B (PKB/AKT; 2.27-fold) and glycogen synthase kinase-3ß (GSK3ß; 2.56-fold), and increased hepatic glycogen content (from 0.19 to 1.65). Furthermore, berberine upregulated the protein expression of peroxisome proliferator activated receptor gamma coactivator 1α (PGC1α; 2.61-fold), phospho-AMP-activated protein kinase (p-AMPK; 1.35-fold) and phospho-liver kinase B1 (p-LKB1; 1.41-fold), whereas it decreased the AMP/ATP ratio (from 4.25 to 1.82).Conclusion: The present study demonstrated the protective effects of berberine against insulin resistance induced by fructose. Our findings may provide an experimental basis for the application of berberine in the treatment of insulin resistance.

Reductive soil disinfestation effectively alleviates the replant failure of Sanqi ginseng through allelochemical degradation and pathogen suppression.

Replant failure has threatened the production of Sanqi ginseng (Panax notoginseng) mainly due to the accumulation of soil-borne pathogens and allelochemicals. Reductive soil disinfestation (RSD) is an effective practice used to eliminate soil-borne pathogens; however, the potential impact of RSD on the degradation of allelochemicals and the growth of replant Sanqi ginseng seedlings remain poorly understood. In this study, RSD was conducted on a Sanqi ginseng monoculture system (SGMS) and a maize-Sanqi ginseng system (MSGS), defined as SGMS_RSD and MSGS_RSD, respectively. The aim was to investigate the impact of RSD on allelochemicals, soil microbiomes, and survival rates of replant seedlings. Both short-term maize planting and RSD treatment significantly degraded the ginsenosides in Sanqi ginseng-cultivated soils, with the degradation rate being higher in the RSD treatment. The population of Fusarium oxysporum and the relative abundance of genus Fusarium were dramatically suppressed by RSD treatment. Furthermore, the RSD treatment, but not maize planting, markedly alleviated the replant failure of Sanqi ginseng, with the seedling survival rate being 52.7-70.7% 6 months after transplanting. Interestingly, RSD followed by short-term maize planting promoted microbial activity restoration, ginsenoside degradation, and ultimately alleviated the replant failure much better than RSD treatment alone (70.7% vs. 52.7%). Collectively, these results indicate that RSD treatment could considerably reduce the obstacles and might also act as a potential agriculture regime for overcoming the replant failure of Sanqi ginseng. Additional practices, such as crop rotation, beneficial microorganism inoculation, etc. may also still be needed to ensure the long-term efficacy of seedling survival.

Selective Separation of Acetic and Hexanoic Acids across Polymer Inclusion Membrane with Ionic Liquids as Carrier.

This paper first reports on the selective separation of volatile fatty acids (VFAs) (acetic and hexanoic acids) using polymer inclusion membranes (PIMs) containing quaternary ammonium and phosphonium ionic liquids (ILs) as the carrier. The affecting parameters such as IL content, VFA concentration, and the initial pH of the feed solution as well as the type and concentration of the stripping solution were investigated. PIMs performed a much higher selective separation performance toward hexanoic acid. The optimal PIM composed of 60 wt% quaternary ammonium IL with the permeability coefficients for acetic and hexanoic acid of 0.72 and 4.38 µm s-1, respectively, was determined. The purity of hexanoic acid obtained in the stripping solution increased with an increase in the VFA concentration of the feed solution and decreasing HCl concentration of the stripping solution. The use of Na2CO3 as the stripping solution and the involvement of the electrodialysis process could dramatically enhance the transport efficiency of both VFAs, but the separation efficiency decreased sharply. Furthermore, a coordinating mechanism containing hydrogen bonding and ion exchange for VFA transport was demonstrated. The highest purity of hexanoic acid (89.3%) in the stripping solution demonstrated that this PIM technology has good prospects for the separation and recovery of VFAs from aqueous solutions.

Adsorption behavior and mechanism of Cr(VI) by modified biochar derived from Enteromorpha prolifera.

Biochar that was derived from Enteromorpha prolifera and magnetically modified (BCF600) was evaluated for its physicochemical properties and Cr(VI) adsorption behavior and mechanism. The results showed that the modified biochar was less porous on surface and loaded with γ-Fe2O3 particles. BCF600 exhibited a maximum adsorption capacity for Cr(VI), which acquired from the Langmuir model of 88.17 mg g-1 and a removal efficiency of 97.71%, for 100 mg L-1 of Cr(VI). The adsorption of Cr(VI) by BCF600 decreased with increasing pH and background ion intensity. Based on the FTIR results, the change in the -OH groups on the surface after adsorption confirmed that electrostatic interaction was likely the preponderant mechanism. In addition, the BCF600 could be easily separated using a magnet and displayed high recyclability. Therefore, this magnetic biochar derived from Enteromorpha prolifera has the potential to serve as a highly efficient adsorbent for water pollution control.

Pirfenidone suppresses MAPK signalling pathway to reverse epithelial-mesenchymal transition and renal fibrosis.

AIM: Recent studies indicate that pirfenidone (PFD) may have anti-fibrotic effects in many tissues, but the potential molecular mechanism remains unknown. The purpose of this study is to investigate the potential effects of PFD on epithelial-to-mesenchymal transition (EMT) and renal fibrosis in a unilateral ureteral obstruction (UUO) rat model and the involved molecular mechanism related to cultured human renal proximal tubular epithelial cells (HK-2). METHODS: Sixty rats were randomly divided into three groups: sham-operated, vehicle-treated UUO, and PFD-treated UUO. Kidney specimens were collected at day 7 or 14 after UUO. PFD treatment was also performed for human HK-2. The tubulointerstitial injury, interstitial collagen deposition, and expression of type I and III collagen, α-SMA, S100A4, fibronection and E-cadherin were assessed. In addition, extracellular signal regulated kinase (ERK1/2), p38 MAPK (p38), and c-Jun N-terminal kinase/stress-activated protein kinase (JNK) were also detected. RESULTS: In vitro, PFD significantly attenuated TGF-ß1-induced EMT and extracellular matrix (ECM) synthesis, as determined by reducing expression of α-SMA, type I and III collagen, S100A4, fibronection, and increased expression of E-cadherin. PFD treatment attenuated TGF-ß1-induced up-regulation of phosphorylation of ERK1/2, p38 and JNK. In vivo, PFD reduced the degree of tubulointerstitial injury and renal fibrosis, which was associated with reduced expression of TGF-ß1, type III collagen, α-SMA, S100A4, fibronection, and increased expression of E-cadherin. CONCLUSION: These results suggest that pirfenidone is able to attenuate EMT and fibrosis in vivo and in vitro through antagonizing the MAPK pathway, providing a potential treatment to alleviate renal tubulointerstitial fibrosis.

Machine learning screening of biomass precursors to prepare biomass carbon for organic wastewater purification: A review.

In the past decades, the amount of biomass waste has continuously increased in human living environments, and it has attracted more and more attention. Biomass is regarded as the most high-quality and cost-effective precursor material for the preparation carbon of adsorbents and catalysts. The application of biomass carbon has extensively explored. The efficient application of biomass carbon in organic wastewater purification were reviewed. With briefly introducing biomass types, the latest progress of Machine learning in guiding the preparation and application of biomass carbon was emphasized. The key factors in constructing efficient biomass carbon for adsorption and catalytic applications were discussed. Based on the functional groups, rich pore structure and active site of biomass carbon, it exhibits high efficiency in water purification performance in the fields of adsorption and catalysis. In addition, out of a firm belief in the enormous potential of biomass carbon, the remaining challenges and future research directions were discussed.

Modified Danzhi XiaoyaoSan inhibits neuroinflammation via regulating TRIM31/NLRP3 inflammasome in the treatment of CUMS depression.

The NLRP3 inflammasome is critically involved in the development of depression. The E3 ubiquitin ligase TRIM31 negatively regulates this process by promoting the degradation of NLRP3 through the ubiquitin-proteasome pathway. Modified Danzhi Xiaoyaosan (MDZXYS) has shown good therapeutic effect in both preclinical and clinical depression treatments, yet the underlying mechanisms of its antidepressant effects are not fully understood. In the present study, we aimed to explore the antidepressant mechanisms of MDZXYS, focusing on NLRP3 activation and ubiquitin-mediated degradation. We employed rats with depression induced by chronic unpredictable mild stress (CUMS) and conducted various behavioral tests, including the sucrose preference, forced swimming, and open field tests. Neuronal damage in CUMS-treated rats was assessed using Nissl staining. We measured proinflammatory cytokine levels using ELISA kits and analyzed NLRP3/TRIM31 protein expression via Western blotting and immunofluorescence staining. Our results disclosed that MDZXYS reversed CUMS-induced depression-like behaviors in rats, reduced proinflammatory cytokine levels (IL-1ß), and ameliorated neuronal damage in the prefrontal cortex. Additionally, CUMS activated the NLRP3 inflammasome in the prefrontal cortex and upregulated the protein expression of TRIM31. After MDZXYS administration, the expression of NLRP3 inflammasome-associated proteins was reduced, while the expression level of TRIM31 was further increased. Through co-localized immunofluorescence staining, we observed a significant elevation in the co-localization expression of NLRP3 and TRIM31 in the prefrontal cortex of the MDZXYS group. These findings suggest that inhibiting NLRP3 inflammasome-mediated neuroinflammation by modulating the TRIM31signaling pathway may underlie the antidepressant effects of MDZXYS, and further support targeting NLRP3 as a novel approach for the prevention and treatment of depression.

Preparation of Ganoderma Lucidum Bran-Based Biological Activated Carbon for Dual-Functional Adsorption and Detection of Copper Ions.

In this paper, Ganoderma lucidum bran was explored as the precursor to fabricate biomass activated carbon. When potassium hydroxide was selected as an activator (1:6, mass ratio of AC-12 to potassium hydroxide), and the activation condition was 700 °C at 5 h, the highest specific surface area reached 3147 m2 g-1. Carbon dots were prepared with citric acid monohydrate and thiourea as precursors and then loaded onto the surface of activated carbon by a simple and green method. Activated carbon for dual-functional had a high adsorption capacity. Additionally, based on its unique optical properties, the fluorescence response for detecting copper ion was established. The fluorescence intensity of the materials decreased linearly with the increase of copper ion concentration, in the range of 10-50 nmol L-1. The research opened up a new way for applying biomass activated carbon in the field of adsorption and detection. Highlights: (1) Carbon dots were loaded on the surface of activated carbon; (2) the simultaneous adsorption and detection were realized; (3) it provides a way for the preparation of dual-functional materials.

Adsorption of heavy metal onto biomass-derived activated carbon: review.

Due to the rapid development of the social economy and the massive increase in population, human beings continue to undertake processing, and commercial manufacturing activities of heavy metals, which has caused serious damage to the environment and human health. Heavy metals lead to serious environmental problems such as soil contamination and water pollution. Human health and the living environment are closely affected by the handling of heavy metals. Researchers must find several simple, economical and practical methods to adsorb heavy metals. Adsorption technology has been recognized as an efficient and economic strategy, exhibiting the advantages of recovering and reusing adsorbents. Biomass-derived activated carbon adsorbents offer large adjustable specific surface area, hierarchically porous structure, strong adsorption capacity, and excellent high economic applicability. This paper focuses on reviewing the preparation methods of biomass-derived activated carbon in the past five years. The application of representative biomass-derived activated carbon in the adsorption of heavy metals preferentially was described to optimize the critical parameters of the activation type of samples and process conditions. The key factors of the adsorbent, the physicochemical properties of the heavy metals, and the adsorption conditions affecting the adsorption of heavy metals are highlighted. In addition, the challenges faced by biomass-derived activated carbon are also discussed.