Inhibitory Effect Research Articles

How digital finance reduces corporate financial restatements: evidence from China

ABSTRACT Digital finance, which combines digital technology with finance, is essential for increasing financial efficiency, enhancing services, and lowering financing costs. It provides enterprises with innovative service models and presents new opportunities for auditors. This study empirically analyses the direct effects, mechanisms, and heterogeneous effects of digital finance on financial restatements, utilizing data from Chinese listed companies between 2011 and 2022. The results demonstrate that digital finance significantly inhibits financial restatements. Both the breadth and depth of digital finance exhibit a suppressive effect on financial restatements, indicating that integrating these factors is essential for maximizing the effectiveness of digital finance in auditing. Internal mechanisms indicate that digital financing reduces corporate financial restatements by improving internal controls. Heterogeneity analyses further reveal that digital finance has a stronger inhibitory effect on financial restatements in small businesses, firms in the eastern region, technology-driven enterprises, and non-state-owned enterprises. These findings provide valuable insights for financial organizations, accounting practices, investors, analysts, and regulatory bodies aiming to enhance the effectiveness of decision-making procedures.

Design, synthesis, and investigation of novel 5-arylpyrazole-glucose hybrids as α-glucosidase inhibitors

Considering the global incidence of diabetes, developing new compounds to lower blood sugar levels has become increasingly crucial. As a result, there has been a growing focus on the synthesis of α-glucosidase inhibitors in recent years. This study investigated design, synthesis, and effects of novel 5-aryl pyrazole-glucose hybrids as α-glucosidase inhibitors. Thirteen derivatives from this class of compounds were synthesized, demonstrating superior in vitro inhibitory effects (IC50 values ranging from 0.5 to 438.6 µM, compared to acarbose at 750.0 µM). Among them, compound 8g (IC50 = 0.5 µM) was selected for further investigations and the kinetic studies revealed that it is a competitive inhibitor (Ki = 0.46 µM). Fluorescence assays indicated changes in the fluorescence intensity, while thermodynamic analyses suggested that compound 8g promoted a transition of the enzyme into an unfolded state. Furthermore, in vivo studies demonstrated that 8g effectively reduced blood sugar levels in rats at doses comparable to acarbose. Molecular docking studies revealed that this compound interacted with the enzyme’s active site, and molecular dynamics simulations showed that pharmacophores engaged in various interactions with the enzyme.

Mitochondria derived from Stem cells modulated the biological behavior of monocyte-macrophages and inhibited inflammatory bone resorption

BackgroundThe transfer of mitochondria from stem cells effectively attenuates the viability of inflammatory cells. However, there is a paucity of research supporting the inhibitory effect of stem cells on inflammatory bone resorption through mitochondrial transfer.MethodsMouse bone resorption models were established to investigate the impact of stem cell-derived mitochondria. Stem cells, stem cell-derived mitochondria and exosomes were injected into the animal models for experimental research. Healthy mice and mice with bone resorption were included as the control groups. The mitochondrial transfer and bone resorption of mice calvaria were evaluated by immunofluorescence, gross morphology, micro-computed tomography (micro-CT), immunohistochemical staining. Monocyte-macrophages were incubated with stem cell-derived mitochondria as experimental group. Monocyte-macrophages and activated monocyte-macrophages cultured separately served as the control groups. The mitochondrial transfer and biological behavior of monocyte-macrophages were evaluated by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), Multiskan FC, and histochemical staining.ResultsStem cell-derived mitochondria were successfully transferred to monocyte-macrophages. In vivo, local injection of stem cells, mitochondria, and exosomes effectively mitigated inflammatory cell infiltration, suppressed osteoclast maturation, and demonstrated a higher relative bone volume in mouse bone resorption models compared to the negative control group. In vitro, the co-incubation of mitochondria effectively suppressed the secretion of inflammatory cytokines, proliferation, fusion, and osteoclastogenesis in monocyte-macrophages compared to the control groups.ConclusionsThe modulation of monocyte-macrophages biological behaviors by stem cells may occur through the transfer of mitochondria, thereby mitigating inflammatory bone resorption.

Age-associated increase in AT1R expression in human testis and its intervention effects on Leydig cell senescence in aged rodents.

The active peptide hormone Ang II (angiotensin II) mediates the vast majority of the RAS (renin-angiotensin system) action, mainly through activation of AT1R (Angiotensin II type-1 receptor). AT1R expression peaks in newborn males and decreases toward the adult age, and it is shown to exhibit an inhibitory effect on hCG (human chorionic gonadotropin)-stimulated steroidogenesis in LCs (Leydig cells), as well as an promoting effect on smooth muscle and endothelial cell senescence. However, whether hyperactivation of the AT1R signaling exerts any effects on Leydig cell senescence, which could provide insights into hypogonadism mechanisms for aging males, remains unexplored. We herein reported that AT1R expression was significantly upregulated in aged human and rat testes. Transgenic overexpression of AT1R in LCs mimicked multiple late-onset hypogonadism phenotypes, including acceleration of Leydig cell senescence, defective steroidogenesis and spermatogenesis, and increased inflammation and oxidative stress. One of the core biochemical events underpinning AT1R action was the AT1R-induced enhancement of the interaction between MDM2 (murine double minute 2) and the p65 subunit of NF-κB (nuclear factor-kappaB), consequently augmenting polyubiquitination and activation of p65, in a p38-dependent manner. Conversely, repression of AT1R activity ameliorated Leydig cell senescence and rescued testicular steroidogenesis in old rats. Together, forced expression of AT1R within the testicular interstitium potentiates aging-related traits in LCs, thereby leading to fertility impairment with defective steroidogenesis and spermatogenesis in male rodents. Our systematic analysis also indicates that blocking the Ang II/AT1R signal might be beneficial in intervening disorders of late-onset hypogonadism in old males.

FDX1 overexpression inhibits the growth and metastasis of clear cell renal cell carcinoma by upregulating FMR1 expression

Kidney cancer has caused more than 150,000 deaths in 185 countries around the world and is a serious threat to human life. Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. FDX1, a crucial gene for regulating copper death, plays an important role in tumors. However, its specific role in ccRCC remains unclear. In this study, by analysing data from the TCGA-KIRC and GEO databases and validation in clinical samples from our center, the expression characteristics of FDX1 and its relationship with tumor clinicopathological features and patient prognosis were clarified; the effects of FDX1 overexpression on ccRCC cell proliferation, apoptosis, migration, and invasion were determined via cell phenotype experiments and mouse orthotopic renal tumor growth models; and the downstream regulatory mechanism of FDX1 was determined via TMT proteomic sequencing, Co-IP assays, and RNA-sequencing detection. Our results confirmed that FDX1 was significantly underexpressed in ccRCC and that reduced FDX1 expression was associated with adverse clinicopathologic features and poor prognosis. FDX1 overexpression markedly inhibited the proliferation, migration, and invasion of ccRCC cells and promoted cell apoptosis in vitro. Mechanistically, FDX1 bound to the FMR1 protein and upregulated its expression, subsequently restraining Bcl-2 and N-cadherin expression and enhancing ALCAM, Cleaved Caspase-3, and E-cadherin expression. In mouse models, FDX1 overexpression significantly suppressed the growth and metastasis of renal tumors, but this inhibitory effect was markedly reversed after FMR1 expression was knocked down. Thus, our results confirmed that FDX1 expression is significantly reduced in ccRCC and serves as a prognostic marker for ccRCC patients and that its overexpression suppresses the growth and metastasis ability of ccRCC by promoting the expression of FRM1.

The role of unsaturated fatty acids in modulating human butyrylcholinesterase activity: insights from kinetics and molecular docking.

Butyrylcholinesterase is an abundant detoxification enzyme in human serum that is mainly synthesized in the liver. It plays a crucial role in the hydrolysis of a variety of choline esters and xenobiotics, and there is emerging evidence that it is also involved in lipid metabolism. In this study, the inhibitory effects of the major unsaturated fatty acids - arachidonic acid (AA), linoleic acid (LA), oleic acid (OA), and alpha-linolenic acid (α-LA) - on human BChE are investigated using enzyme kinetics experiments and molecular modeling analyses. These fatty acids, integral components of membrane phospholipids, differ in chain length and degree of unsaturation, which influence their inhibitory effect on BChE. Our results showed that AA had the highest IC₅₀ value of 611µM against BChE, followed by OA, α-LA, and LA. All fatty acids showed noncompetitive inhibition, in contrast to AA, which displayed uncompetitive inhibition. Inhibitory constants (Ki) showed that OA had the strongest binding affinity due to its lowest Ki value of 321.4µM, followed by AA, α-LA, and LA. Molecular modeling supported the in vitro results. The fatty acids were predicted to bind to a newly proposed allosteric site on BChE. Our results demonstrate that the number and position of double bonds in the alkenyl chains of fatty acids significantly influence their interactions with BChE, providing new insights into how dietary lipids regulate the enzyme. This study offers a foundation for further exploration of BChE's role in lipid metabolism and its implications for neurodegenerative and metabolic diseases.

Mechanisms of rifaximin inhibition of hepatic fibrosis in mice with metabolic dysfunction associated steatohepatitis through the TLR4/NFκB pathway

Metabolic dysfunction-associated steatohepatitis (MASH) has become a serious public health problem, posing an increasingly dangerous threat to human health owing to its increasing prevalence and accompanying intra- and extrahepatic adverse outcomes. Rifaximin is considered to have therapeutic potential for MASH; however, its efficacy remains controversial. Our study aimed to observe the ameliorative effects of rifaximin and explore its possible mechanisms at the cellular level. 1. 42 male C57BL/6J mice were divided into 3 groups, the CON group and MCD group were fed with normal feed and MCD feed for 12 weeks respectively, and the MCD + RFX group was treated with rifaximin by gavage for 4 weeks on the basis of MCD feed. Hematoxylin-eosin staining, Sirius red staining and immunohistochemical staining were used to observe the histopathological changes of liver and intestine. Differences in liver transaminases, inflammatory factors, fibrosis indexes and intestinal tight junction proteins were compared among the 3 groups of mice. 2. A MASH cell model was constructed by inducing HepG2 cells with free fatty acids to observe the effects of rifaximin on MASH in vitro. In addition, the effects of rifaximin on TLR4/NF-κB signaling pathway were explored by applying TLR4 agonist LPS and TLR4 inhibitor TAK-242. Hepatic histopathology was significantly improved in MASH mice after rifaximin treatment, and their serum alanine aminotransferase and aspartate aminotransferase levels were (72.72 ± 5.68) U/L and (222.8 ± 11.22) U/L, respectively, which were significantly lower than those in the MCD group [(293.3 ± 10.69) U/L and (414.1 ± 36.29) U/L, P < 0.05], and the levels of inflammatory factors and fibrosis indicators were reduced. Rifaximin ameliorated intestinal barrier injury with increased expression of intestinal tight junction protein ZO-1 in the MCD + RFX group of mice, and the concentration of LPS-binding proteins (4.92 ± 0.55 vs. 15.82 ± 1.71, P < 0.05) was lower than that in the MCD group. In the NASH cell model, rifaximin similarly exerted inhibitory effects on its inflammatory factors and TLR4/NF-κB signaling pathway. Application of TLR4 inhibitors weakened the inhibitory effect of rifaximin on MASH. Our study supports rifaximin as a potential treatment for MASH, with potential mechanisms related to improving intestinal barrier integrity and downregulating the TLR4/NF-κB signaling pathway.

Synthesis, in vitro, and in silico studies of 7-fluorochromone based thiosemicarbazones as α-glucosidase inhibitors

Increased blood sugar is a typical manifestation of Type-2 Diabetes Mellitus (T2DM), a metabolic disorder that can be effectively managed with the help of α-glucosidase inhibitors. A range of new chromone based thiosemicarbazone derivatives (3a-t) was synthesized and assessed due to their ability to suppress α-glucosidase in this research. Having IC50 values spanning from 6.40 ± 0.15 to 62.81 ± 0.79 μM, the compounds demonstrated strong inhibitory actions. The compound 3 k showed the most inhibitory effect among all of them, by an IC50 measurement of 6.40 ± 0.15 µM. It was concluded through a structure–activity relationship (SAR) assessment that various substituents on thiosemicarbazone moieties had a significant impact on the differences in α-glucosidase inhibition. Molecular docking experiments provide light on important interactions, including π-π interactions and hydrogen bridges, between compounds and role of the carbothioamide and chromenyl groups in ligand attachment to the critical residues of α-glucosidase. The binding interactions, alignment, stability, and structural arrangement of the prepared molecules in the catalytic pocket of α-glucosidase were explored using in silico strategies such as docking studies, pharmacokinetic analysis, and molecular dynamics simulations. This investigation directed to find compounds with favorable profiles for future progress as potential therapeutic agents for type 2 diabetes. Importantly, when benchmarking against acarbose, the lead candidate showed substantially greater efficacy.

Pirfenidone alleviates interstitial lung disease in mice by inhibiting neutrophil extracellular trap formation and NLRP3 inflammasome activation.

Idiopathic inflammatory myopathy (IIM) is a progressive autoimmune disease characterized by interstitial lung disease (ILD) with limited therapeutics available. Pirfenidone (PFD), a medication utilized for the treatment of idiopathic pulmonary fibrosis, exhibits notable antioxidant, anti-inflammatory and inhibition of collagen synthesis. This study aims to clarify its efficacy and mechanism in treating IIM-ILD. A murine myositis-associated interstitial lung disease (MAILD) model was used to assess the therapeutic effect of PFD. The serum levels of IL-1β, IL-6 and TNF-α were detected by ELISA. PFD was utilized to disrupt neutrophil extracellular traps (NETs) formation in vitro, and its inhibitory effect on NETs was assessed through immunohistochemistry of CitH3 and MPO in the lung tissue and the serum cfDNA level in mice. Immunohistochemical and western blot was utilized to examine alterations in epithelial-mesenchymal transition (EMT) and NLRP3 inflammasome markers. PFD treatment inhibited pulmonary inflammation and fibrosis in the MAILD model. PFD intervention reduced NETs formation in vitro. PFD treatment significantly reduce NETs infiltration in the lung tissue and the level of cfDNA in the serum of mice. Additionally, PFD down-regulated EMT and NLRP3-related proteins in vivo. PFD treatment also notably reduced serum levels of IL-1β, IL-6 and TNF-α. After NETs stimulation, A549 cells exhibited EMT and activation of NLRP3 inflammasome. PFD attenuated EMT in A549 cells and suppressed the activation of NLRP3 inflammasome. PFD alleviates ILD in a murine MAILD model by inhibiting NETs formation and NLRP3 inflammasome activation, suggesting that PFD might be a potential therapeutic agent for IIM-ILD.

Crystalline 1D Coordination Polymer Inhibitor Layer Leads to Vertical Sidewalls in Selectively Deposited ZnO on Nanoscale Patterns.

Area-selective atomic layer deposition (AS-ALD) is a promising technique for the fabrication of next-generation nanoelectronics. There are two main challenges in AS-ALD: (1) achieving high selectivity of deposition on the growth regions, and (2) preventing mushrooming of the growth material onto the nongrowth regions and achieving well-defined interfaces. In this work, we use benzenethiol (BT) as an inhibitor in the selective deposition of ZnO on SiO2 in the presence of copper with and without a native oxide (Cu/CuOx). We observe that BT forms a monolayer on the Cu surface and a Cu-thiolate multilayer structure on CuOx. Using grazing incidence X-ray diffraction combined with simulations, we find that the multilayer structure is crystalline and composed of 1D coordination polymers of Cu-thiolate. Using ellipsometry and X-ray photoelectron spectroscopy, we show that the BT consumes the entirety of the CuOx during multilayer formation, allowing the multilayer thickness to be tuned by the thickness of the original oxide. Both the monolayer BT and the multilayer BT prove to be effective inhibitors of ZnO ALD, blocking nearly 500 ALD cycles, which is more than twice that achieved with other thiol inhibitors. Finally, we demonstrate that the multilayer structure can prevent mushrooming of the ALD material onto the nongrowth surface of nanoscale patterns, creating vertical sidewalls with well-defined material interfaces and providing excellent pattern transfer, even for a relatively thick deposited film. As such, these results demonstrate that BT is not only an effective inhibitor but also that its ability to form tunable multilayers makes it well-suited for highly precise nanopatterning applications.

Evaluation of leukemic stem cell (CD26 +) in chronic myeloid leukemia patients with different molecular responses and in treatment-free remission

CD26 + leukemic stem cells (LSC) are a specific marker for chronic myeloid leukemia (CML), absent in healthy individuals and other myeloid neoplasms. These cells can contribute to disease resistance, as they are believed to sustain the leukemic clone despite effective tyrosine kinase inhibitor (TKI) therapy. This study analyzed CD26 + LSC and BCR::ABL1 transcript levels simultaneously using multiparametric flow cytometry and RT-qPCR in 210 chronic-phase patients undergoing TKI therapy and 31 patients in treatment-free remission (TFR). A significant decrease in LSC levels was observed as patients achieved deep molecular response (DMR, BCR::ABL1IS ≤ 0.01%) (χ2, p < 0.001). However, 19% (14/73) of DMR patients displayed persistent CD26 + LSC, suggesting a quiescent state without detectable BCR::ABL1 transcripts. A weak correlation (r = 0.187, p = 0.046) between LSC/µL absolute number and BCR::ABL1 transcript levels indicates a limited predictive value between these two variables. In TFR patients, LSC recurrence during follow-up did not correlate with molecular relapse, questioning their clinical relevance in this setting. In conclusion, while CD26 + LSC are frequently observed in patients with poor molecular response, their levels significantly decrease as patients achieve DMR. However, their persistence or recurrence in TFR lacks prognostic value for molecular relapse, indicating that CD26 + LSC are not reliable predictors of outcomes in CML.

Identification of Bioactive Compounds from Citri Reticulatae Pericarpium and Evaluation of Their Uric Acid-Lowering Activity.

Citri Reticulatae Pericarpium, the dried and mature peel of wild Citrus reticulata Blanco and its cultivated varieties in the rutaceae family, is an important herb and condiment in Chinese medicine. At present, there are few relevant reports, especially in-depth reports, on the discovery of effective anti-gout natural products from CRP. In this study, four compounds were extracted and characterized from CRP using 70% ethanol, RP-C18, thin layer chromatography (TLC), Sephadex LH-20, high performance liquid chromatography (HPLC), and nuclear magnetic resonance spectroscopy (NMR). Additionally, monomer compounds (apigenin, luteolin) in CRP, along with those isolated from CRP, were investigated through molecular docking and in vitro assessment of their XOD inhibitory activity. Notably, the lowest binding energy (-10.3 kcal/mol) and IC50 value (76.24 µg/mL) denoted a strong inhibitory effect of isosakuranetin with XOD. Further studies showed that isosakuranetin could significantly reduce XOD activity and uric acid levels in xanthine-induced BRL-3A cells. This research elucidates, for the first time, the uric acid-lowering effects of isosakuranetin, offering valuable insights into the potential mechanisms underlying its properties. This study provides a basis for the development of uric acid-lowering products from CRP and in-depth mechanism research of uric acid-lowering compounds.

Comparison of anti-inflammatory and anti-angiogenic effects of JAK inhibitors in IL-6 and TNFα-stimulated fibroblast-like synoviocytes derived from patients with RA

Rheumatoid arthritis (RA) involves synovial tissue proliferation, inflammation, and angiogenesis, and contributes to joint destruction. Angiogenesis is a key therapeutic target for the treatment of RA, and Janus kinase (JAK) inhibitors have emerged as a promising therapy. In this study, we compared the inhibitory effects of five JAK inhibitors, including tofacitinib (TOF), baricitinib, peficitinib, upadacitinib, and filgotinib, on interleukin (IL)-6-induced inflammation in RA synovial tissues. All five inhibitors effectively suppressed IL-6-induced inflammatory and angiogenic factors, including vascular endothelial growth factor, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3. Overall, the results suggest that while all five JAK inhibitors are effective in reducing IL-6-induced inflammatory and angiogenic factors, their efficacy may differ owing to specific molecular mechanisms and pharmacological properties.

Research on the Inhibitory Effect of Financial Literacy on Preventing Victims of Fraud

Research on the Inhibitory Effect of Financial Literacy on Preventing Victims of Fraud

Dioscin alleviates the dysfunction of fibroblast-like synoviocytes by circ_0008267/miR-942-5p/FKBP5 axis during rheumatoid arthritis.

Dioscin is a natural, bioactive steroid saponin that has the antiarthritic activity. Circular RNAs (circRNAs) are stable noncoding RNAs involving in the pathogenesis of rheumatoid arthritis (RA). Here, this study aimed to probe the role and mechanism of dioscin and circ_0008267 in RA progression. Cell proliferation, apoptosis, invasive, and migratory abilities, as well as inflammatory response were evaluated by CCK-8 assay, EdU assay, flow cytometery, transwell assay, wound healing assay, and ELISA analysis, respectively. Levels of genes and protein were tested by qRT-PCR and western blotting. The interaction between miR-942-5p and circ_0008267 or FK506-binding protein 5 (FKBP5) was confirmed using dual-luciferase reporter and RNA pull-down assays. Dioscin treatment was demonstrated to suppress RA-FLS proliferation, invasion, migration, and inflammatory response, but induced cell apoptosis. Circ_0008267 is a stable circRNA, and was increased in RA samples. Moreover, its expression was reduced by dioscin in RA-FLS, overexpression of circ_0008267 reversed the effects of dioscin on RA-FLS. Mechanistically, circ_0008267 acted as a sponge for miR-942-5p, which targeted FKBP5. Dioscin reduced FKBP5 expression, but elevated miR-942-5p level in RA-FLS. MiR-942-5p inhibition or FKBP5 upregulation abolished the inhibitory effects of dioscin on RA-FLS dysfunction. Moreover, circ_0008267 deficiency impaired RA-FLS proliferation, invasion, migration, and inflammation through regulating FKBP5. Dioscin suppressed the proliferation, invasion, migration, and inflammatory response in RA-FLS via circ_0008267/miR-942-5p/FKBP5 axis, providing new insights for RA prevention.

Suppression of ATP-dependent (S)-NAD(P)H-hydrate dehydratase expression inhibits adipocyte differentiation of 3T3-L1 preadipocytes by increasing excessive accumulation of NADHX.

ATP-dependent (S)-NAD(P)H-hydrate dehydratase (NAXD) is a crucial enzyme in the nicotinamide adenine dinucleotide repair system that regenerates NAD(P)H, an essential electron donor in metabolic redox reactions. NAD+-related metabolic pathways connect cellular metabolism and the expression of genes responsible for adipogenesis; however, the biological significance of the NAXD-mediated repair pathway remains unclear. Herein, we showed that NAXD is essential for normal adipocyte differentiation of 3T3-L1 murine preadipocytes. Silencing of the Naxd gene attenuated differentiation-induced lipid accumulation with excessive accumulation of hydrated NADH (NADHX) without altering NAD+ levels. FK866, a specific inhibitor of NAMPT, further reduced lipid accumulation even in Naxd-silenced cells with substantial decrease in NAD+. Supplementation with nicotinamide mononucleotide, a precursor of NAD+, restored NAD+ levels comparably in Naxd- and LacZ-silenced cells treated with FK866, but failed to recover adipocyte differentiation of Naxd-silenced cells to the level of LacZ-silenced cells. In contrast, exposure of wild-type 3T3-L1 cells to NADHX recapitulated the Naxd deficiency-elicited inhibitory effects on adipocyte differentiation with reduced expression of master transcriptional regulators of adipogenesis, peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α. These results suggest that NAXD supports normal adipogenesis, in part, by inhibiting excessive accumulation of NADHX.

Computational Screening of IL-1 and IL-6 Inhibitors for Rheumatoid Arthritis: Insights from Molecular Docking and Dynamics Analysis.

Rheumatoid arthritis (RA) remains a significant therapeutic challenge due to its chronic inflammatory nature. Consequently, many patients turn to alternative therapies, such as herbal compounds and supplements, when conventional treatments prove relatively ineffective or cause adverse side effects. Some compounds are being investigated for their potential to alleviate RA symptoms or manage disease. This study aimed to evaluate the anti-inflammatory effects of selected herbal compounds targeting the Interleukin-1 (IL-1) and Interleukin-6 (IL-6) pathways, key inflammatory regulators in RA. Specifically, the study assessed the binding affinity, stability, and dynamics of IL-1 and IL-6 inhibitory compounds as potential therapeutic agents for RA. In silico experiments were conducted with herbal compounds to modulate IL-1 and IL-6 signaling. Computational techniques, including molecular docking, molecular dynamics (MD) simulations, Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) calculations, Absorption, Distribution, Metabolism, and Excretion (ADME) analysis, toxicity predictions, and Density Functional Theory (DFT) analysis, were employed to investigate these interactions comprehensively. Neoglucobrassicin demonstrated the strongest binding affinity for IL-6 (Total score: -349.00 kJ/mol), followed by Galbelgin (-338.00 kJ/mol). For IL-1β, CID21722980 exhibited the highest binding affinity (-273.14 kJ/mol), with Eupaformosanin ranking second (-264.29 kJ/mol). Neoglucobrassicin formed interactions with multiple IL-6 residues, indicating a stable binding complex, while CID21722980 similarly interacted with key IL-1β residues, forming stable complexes. Both the Neoglucobrassicin-IL6 and CID21722980- IL1β complexes demonstrated structural stability, as evidenced by Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) stabilizing towards the end of the 100 ns molecular dynamics (MD) simulation. MM-GBSA analysis revealed the highest binding energy for the IL-6-Neoglucobrassicin complex (-43.70 kcal/mol), while CID21722980 showed strong affinity for IL-1β (-43.29 kcal/mol), suggesting enhanced binding potential. Additionally, Density Functional Theory (DFT) analysis of the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energies revealed electron distribution patterns in Neoglucobrassicin and CID21722980 that support their potential therapeutic applications. The strong binding affinities, stable molecular dynamics (MD) simulations, and favorable ADMET and DFT properties of Neoglucobrassicin and CID21722980 underscore their potential as antiinflammatory agents targeting IL-6 and IL-1β. The mechanistic insights into their inhibitory effects on these targets suggest multifaceted anti-inflammatory properties, warranting further in vivo and clinical investigations. Neoglucobrassicin and CID21722980 demonstrated promising binding affinities, favorable pharmacokinetic profiles, and advantageous electronic properties, positioning them as strong candidates for further exploration in anti-inflammatory therapies. These findings highlight the potential of these herbal compounds as modulators of IL-6 and IL-1β, paving the way for future drug development.

Tanshinone IIA affects the proliferation of A549/Tax by affecting the expression of MMP7 through the PI3K-AKT-mTOR signaling pathway

ObjectiveThis study aims to explore whether tanshinone IIA can act on paclitaxel-resistant non-small cell lung cancer A549/Tax and analyze the possible mechanisms involved.MethodsUsing the Cell Counting Kit-8 (CCK-8), we preliminarily analyzed whether tanshinone IIA has an inhibitory effect on A549/Tax cells. We utilized public datasets, self-collected transcriptome datasets, and drug target analysis to identify potential targets. We employed real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) to detect the expression of core genes before and after drug treatment to analyze potential target genes and validated them using data from The Cancer Genome Atlas (TCGA). We conducted enrichment analysis on co-expressed genes of the target genes to explore potential mechanisms. Furthermore, we employed molecular docking and western blot to verify the possible mechanisms involved.ResultsThe CCK8 results indicated that tanshinone IIA has a significant inhibitory effect on A549/Tax cells. The qPCR results and the analysis of TCGA data indicated that MMP7 is the target gene. Enrichment results of MMP7 co-expressed genes suggested that the PI3K-AKT signaling pathway might play a key role. Molecular docking results indicated that tanshinone IIA has strong binding activity with PI3K, AKT, mTOR, and MMP7. Western blotting results showed that tanshinone IIA might inhibit MMP7 through the PI3K-AKT-mTOR signaling pathway.ConclusionsTanshinone IIA may affect the proliferation of A549/Tax by influencing the expression of MMP7 through the PI3K-AKT-mTOR signaling pathway.

Phytochemical composition, antioxidant and enzyme inhibitory effects of Stahlianthus thorelii Gagnep. rhizomes.

Stahlianthus thorelii Gagnep. is used in traditional medicine to treat various diseases. In this study, ethyl acetate (EtOAc) extract of S. thorelii rhizomes was analyzed for its phychemicals, antioxidant activity and inhibition against enzymes (acetylcholinesterase, α-amylase, α-glucosidase, and tyrosinase). The EtOAc extract showed the presence of ferulic acid, catechin, epicatechin, epigallocatechin gallate, quercetin, and kaempferol, with average levels ranging from 169.29 to 2449.60 μg/g. Analysis of the volatile components of the extract revealed that β-patchoulene (23.1%), (E)-nerolidyl isobutyrate (11.9%), and aristolene (10.8%) were the major compounds. The antioxidant potential of the extract measured by DPPH (IC50 = 86.94 ± 2.87 μg/mL) and ABTS (IC50 = 743.60 ± 56.52 μg/mL) assays showed promising results. The inhibitory effects against acetylcholinesterase and α-amylase demonstrated potential with IC50 values of 246.43 ± 11.39 and 789.84 ± 8.27 µg/mL, respectively. The findings above suggest that the EtOAc extract of S. thorelii could contribute to supporting the treatment of certain diseases such as diabetes and Alzheimer's.

The Effect of Platelet-Rich Plasma on Synovial Fibrosis and Cartilage Degeneration in Knee Osteoarthritis.

Synovial fibrosis is a prevalent pathological feature of osteoarthritis and a primary contributor to joint pain and stiffness. Studies indicate that platelet-rich plasma (PRP) is rich in growth factors and cytokines, exhibiting anti-inflammatory, anti-apoptotic, chemotactic, and proliferative properties that can facilitate tissue repair. However, little is known about its effect on synovial fibrosis in knee osteoarthritis (KOA). To determine the effect of PRP on synovial fibrosis and cartilage degeneration in KOA. Controlled laboratory study. Anterior cruciate ligament transection was performed to induce KOA in male Sprague-Dawley rats, and then rats were randomly assigned to 4 different groups: sham operation, KOA only, KOA treated with phosphate-buffered saline (PBS), and KOA treated with PRP. Synovial collagen fiber deposition was observed using Masson and Sirius red staining, and synovial inflammation was assessed using hematoxylin and eosin (H&E) staining. Moreover, immunohistochemistry was conducted to analyze the expression of synovial fibrosis-related factors including PLOD2, COL1A1, TIMP1, TGF-β1, and α-SMA. KOA severity and articular cartilage degradation were assessed using micro-computed tomography (micro-CT), safranin O-fast green staining, H&E staining, immunohistochemistry, and the Osteoarthritis Research Society International (OARSI) criteria. A quantitative analysis of growth factors (platelet-derived growth factor, IGF-1, epidermal growth factor, TGF-β1, fibroblast growth factor, and endothelial growth factor) in activated PRP was performed using enzyme-linked immunosorbent assay. Micro-CT imaging and histological staining showed that the KOA model had been successfully established. Compared with the KOA and PBS groups, Masson staining and Sirius red staining results showed that PRP aggravated the degree of synovial fibrosis, which was consistent with the results of immunohistochemistry analysis. Immunohistochemistry analysis showed that PRP promoted the protein expression of PLOD2, COL1A1, TIMP1, TGF-β1, and α-SMA, indicating that the degree of fibrosis was aggravated. However, the PRP group showed lower OARSI and synovitis scores, as well as attenuated abnormal tibial subchondral bone remodeling, suggesting that PRP inhibited further cartilage degeneration and synovial inflammation and improved the subchondral bone microarchitecture. PRP may aggravate KOA synovial fibrosis, but it still has an inhibitory effect on cartilage degeneration and abnormal subchondral bone remodeling. Synovial fibrosis is a significant pathological feature in KOA that is closely linked to clinical symptoms like joint pain and stiffness. This study offers insights into enhancing the effectiveness of PRP therapy for patients with KOA.