Inhibitor Type Research Articles

Probing the efficiency and mechanism of hydrogen permeation inhibition in pipeline steel by organic inhibitors

A hydrogen economy will require the use of steel pipelines to transport and store hydrogen. Methods and materials are urgently needed to prevent the embrittlement of steel pipelines in hydrogen service. In this work, we show that hydrogen permeation into pipeline steel can be mitigated by organic inhibitors, as demonstrated by a typical organic inhibitor benzotriazole (BTA) under simulated X65 steel pipeline cathodic protection conditions. Electrochemical and surface analytical techniques were used to probe the efficiency and mechanism of hydrogen permeation inhibition. In particular, a novel multi-electrode array method was designed to probe the inhibitor film by measuring local impedance and hydrogen charging currents. The ability and efficiency of BTA to inhibit hydrogen permeation were found to be closely associated with the formation and coverage of inhibitor films on steel surfaces. A model is proposed to illustrate the mechanism of hydrogen permeation inhibition by organic inhibitors.

Quercetin Attenuates Acetaldehyde-Induced Cytotoxicity via the Heme Oxygenase-1-Dependent Antioxidant Mechanism in Hepatocytes.

It is still unclear whether or how quercetin influences the toxic events induced by acetaldehyde in hepatocytes, though quercetin has been reported to mitigate alcohol-induced mouse liver injury. In this study, we evaluated the modulating effect of quercetin on the cytotoxicity induced by acetaldehyde in mouse hepatoma Hepa1c1c7 cells, the frequently used cellular hepatocyte model. The pretreatment with quercetin significantly inhibited the cytotoxicity induced by acetaldehyde. The treatment with quercetin itself had an ability to enhance the total ALDH activity, as well as the ALDH1A1 and ALDH3A1 gene expressions. The acetaldehyde treatment significantly enhanced the intracellular reactive oxygen species (ROS) level, whereas the quercetin pretreatment dose-dependently inhibited it. Accordingly, the treatment with quercetin itself significantly up-regulated the representative intracellular antioxidant-related gene expressions, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase, catalytic subunit (GCLC), and cystine/glutamate exchanger (xCT), that coincided with the enhancement of the total intracellular glutathione (GSH) level. Tin protoporphyrin IX (SNPP), a typical HO-1 inhibitor, restored the quercetin-induced reduction in the intracellular ROS level, whereas buthionine sulphoximine, a representative GSH biosynthesis inhibitor, did not. SNPP also cancelled the quercetin-induced cytoprotection against acetaldehyde. These results suggest that the low-molecular-weight antioxidants produced by the HO-1 enzymatic reaction are mainly attributable to quercetin-induced cytoprotection.

Identification of small molecule inhibitors of the Chloracidobacterium thermophilum type IV pilus protein PilB by ensemble virtual screening

Antivirulence strategy has been explored as an alternative to traditional antibiotic development. The bacterial type IV pilus is a virulence factor involved in host invasion and colonization in many antibiotic resistant pathogens. The PilB ATPase hydrolyzes ATP to drive the assembly of the pilus filament from pilin subunits. We evaluated Chloracidobacterium thermophilum PilB (CtPilB) as a model for structure-based virtual screening by molecular docking and molecular dynamics (MD) simulations. A hexameric structure of CtPilB was generated through homology modeling based on an existing crystal structure of a PilB from Geobacter metallireducens. Four representative structures were obtained from molecular dynamics simulations to examine the conformational plasticity of PilB and improve docking analyses by ensemble docking. Structural analyses after 1 μs of simulation revealed conformational changes in individual PilB subunits are dependent on ligand presence. Further, ensemble virtual screening of a library of 4234 compounds retrieved from the ZINC15 database identified five promising PilB inhibitors. Molecular docking and binding analyses using the four representative structures from MD simulations revealed that top-ranked compounds interact with multiple Walker A residues, one Asp-box residue, and one arginine finger, indicating these are key residues in inhibitor binding within the ATP binding pocket. The use of multiple conformations in molecular screening can provide greater insight into compound flexibility within receptor sites and better inform future drug development for therapeutics targeting the type IV pilus assembly ATPase.

Inhibition of TFEB deacetylation in proximal tubular epithelial cells (TECs) promotes TFEB activation and alleviates TEC damage in diabetic kidney disease.

The inhibition of the autophagolysosomal pathway mediated by transcription factor EB (TFEB) inactivation in proximal tubular epithelial cells (TECs) is a key mechanism of TEC injury in diabetic kidney disease (DKD). Acetylation is a novel mechanism that regulates TFEB activity. However, there are currently no studies on whether the adjustment of the acetylation level of TFEB can reduce the damage of diabetic TECs. In this study, we investigated the effect of Trichostatin A (TSA), a typical deacetylase inhibitor, on TFEB activity and damage to TECs in both invivo and invitro models of DKD. Here, we show that TSA treatment can alleviate the pathological damage of glomeruli and renal tubules and delay the DKD progression in db/db mice, which is associated with the increased expression of TFEB and its downstream genes. Invitro studies further confirmed that TSA treatment can upregulate the acetylation level of TFEB, promote its nuclear translocation, and activate the expression of its downstream genes, thereby reducing the apoptosis level of TECs. TFEB deletion or HDAC6 knockdown in TECs can counteract the activation effect of TSA on autophagolysosomal pathway. We also found that TFEB enhances the transcription of Tfeb through binding to its promoter and promotes its own expression. Our results, thus, provide a novel therapeutic mechanism for DKD that the alleviation of TEC damage by activating the autophagic lysosomal pathway through upregulating TFEB acetylation can, thus, delay DKD progression.

Investigation of the energy gap and anti-corrosion activities of triethanolamine lauryl sulfate for carbon steel in 1.0 M HCl using DFT theory and electrochemical studies

Corrosion inhibition is a critical strategy in the industry to mitigate the detrimental effects of corrosion. Green inhibitors are a concern and are encouraged to apply in various ways. Triethanolamine lauryl sulfate (TLS) investigates as a green corrosion inhibition for carbon steel in 1 M HCl using weight loss and electrochemical measurements. A weight loss study revealed that 100 μM of TLS had the highest inhibition effectiveness of 95.7 %. Tafel estimations from the polarization profiles showed that 100 μM had an optimal inhibition effectiveness of about 96.3 %. The physical adsorption of TLS on the carbon steel surface, which followed the Langmuir adsorption isotherm, was ascribed to the inhibitive effect. The results declare that TLS functioned as an inhibitor of mixed types. For TLS, the adsorption Gibb's free energy is −19.6 kJ mol−1, indicating spontaneous and physisorption-based. The energy gap of TLS is evaluated theoretically using density functional theory (DFT), and a lower value indicates its great donation ability of electron’s to the carbon steel. The mechanism of adsorption of TLS onto the metal surfaces is illustrated in terms of experimental and theoretical calculations.

Nicotinic Acid Derivatives As Novel Noncompetitive α-Amylase and α-Glucosidase Inhibitors for Type 2 Diabetes Treatment.

A library of novel nicotinic acid derivatives, focusing on the modification of position 6 of the pyridine ring with (thio)ether functionalities, was mostly produced through an innovative green synthetic approach (Cyrene-based) and evaluated for their α-amylase and α-glucosidase inhibitory activity. Compounds 8 and 44 demonstrated micromolar inhibition against α-amylase (IC50 of 20.5 and 58.1 μM, respectively), with 44 exhibiting a remarkable ∼72% enzyme inactivation level, surpassing the efficacy of the control compound, acarbose. Conversely, 35 and 39 exhibited comparable inhibition values to acarbose against α-glucosidase (IC50 of 32.9 and 26.4 μM, respectively) and a significant enhancement in enzyme inhibition at saturation (∼80-90%). Mechanistic studies revealed that the most promising compounds operated through a noncompetitive inhibition mechanism for both α-amylase and α-glucosidase, offering advantages for function regulation over competitive inhibitors. These inhibitors may open a new perspective for the development of improved hypoglycemic agents for type 2 diabetes treatment.

Anticorrosive activity of Melothria perpusilla: A renewable and sustainable inhibitor

Anticorrosive activity of Melothria perpusilla extract on mild steel in H2SO4 was examined by weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy methods. The results revealed that mild steel corrosion was effectively controlled by the extract with 99.4 % efficiency at 3000mg/L concentration. The efficiency was improved with higher extract concentration but decreased as the temperature increased. The Tafel plots and its corrosion potential value (<85 mV) inferred that Melothria perpusilla acts as a mixed type inhibitor. Adsorption of phytochemicals onto the surface of mild steel is the primary factor in reducing corrosion. The increase in activation energy for adsorption from 22.73 kJ mol−1 in acid to 133.74 kJ mol−1 in extract's presence confirms the active role of phytochemicals in adsorption process. The increase in charge transfer resistance from 3.21 Ω cm2 in acid to 369.2 Ω cm2 in extract's presence, coupled with a decrease in double layer capacitance in the EIS investigation, suggests that a charge transfer mechanism is active at the mild steel-solution interface. Gas chromatography-Mass spectroscopy revealed the presence of five major phytochemicals along with other organic compounds in the extract. Fourier transform infrared and UV–visible spectroscopies indicated the active functional moieties (-COOH, –CONH2, -C-O-C-, –C=C- and long chain alkyl groups) are involved in the inhibition. Scanning electron microscopy confirmed the existence of shielding film of phytochemicals on mild steel. Density functional theory validated the inhibitory properties of the constituents. Therefore, it is concluded that Melothria perpusilla is an efficient green inhibitor in acidic condition.

Development of novel pyrazole-1,2,4-triazole derivatives as tyrosinase inhibitors: Design, preparation, mechanism of action and anti-browning application

Tyrosinase (Polyphenol oxidase), a key enzyme in enzymatic browning, is an attractive target for developing new anti-browning agents in the food industry. In this work, twenty pyrazole-1,2,4-triazole derivatives (3a-3n, 4a-4f) were synthesized and tested in vitro, most of compounds showed potent anti-tyrosinase activity. Of these, 3c (IC50 = 1.02 ± 0.08 μM) was found to be 14 folds stronger than kojic acid (IC50 = 14.74 ± 1.23 μM) and behaved as a mixed type inhibitor. Besides, the disappeared peak of dopaquinone in the HPLC assay intuitively validated the inhibitory effect of 3c. Copper ions chelating, fluorescence quenching and molecular docking assays showed that coordination with copper is the key to play a role. Furthermore, 3c exhibited excellent anti-browning ability for the Rosa roxburghii Tratt, the non-enzymatic browning experiment showed that 3c could prevent browning in non-enzymatic ways. It is suggested that these derivatives could serve as the leading compounds to find more efficient anti-browning agents in the future.

Insights into corrosion inhibition of aluminum in hydrochloric acid solutions using expired cephalosporins and klavox: Chemical, electrochemical and theoretical approaches

The inhibitory efficacy of two expired antibiotic drugs namely, cephalosporin and klavox against corrosion of aluminum in 1.0 M HCl solution was investigate utilizing potentiodynamic polarization (PDP) impedance spectroscopy (EIS) and weight reduction (WR) methodologies. It was discovered that the two expired drugs act as excellent inhibitors and the inhibition efficacy increases as the drug concentration increases and the temperature decreases. The inhibition efficacy reached 97.62 % and 99.42 % at 900 ppm of cephalosporin and klavox at 298 K, respectively. Expired drugs act as a mixed type inhibitor, controlling primarily the anodic and cathodic process, as evidenced by the PDP curves. According to EIS analysis, the charge transfer resistance values increased with increasing inhibitor concentration. The adsorption isotherm demonstrates that the expired drugs become active by physical adsorption on the Al surface, and their adsorption obeys the Langmuir isotherm. Through quantum chemistry calculations, the relationship between the inhibition properties and molecular structure was studied.

Assessing the potential of fedaleh (Echinophora cinerea) essential oils as a natural herbicide for spring-summer crops

Large quantities of chemical herbicides are used in agroecosystems every year, which not only imposes a significant financial burden on farmers but also leads to environmental pollution. To address this challenge, the present study aimed to replace Treflan with Fedaleh essential oils (EO). Treflan is a commonly used chemical herbicide for spring-summer crops, and Chenopodium album has been chosen as a prevalent and abundant weed in many agricultural ecosystems. Four types of inhibitors, including Treflan herbicide and essential oils extracted from the leaf, stem, and flower of Fedaleh, were used in this experiment. These inhibitors were tested at five different concentrations: 0, 0.5, 1, 2, and 5 μL/mL. Based on GC-MS results, the key compounds found in Fedaleh EO were α-pinene, α-phellandrene, γ-terpinene, linalool, sabinol, β-myrcene, neric acid, carvacrol, β-phellandrene, thymol, and spathulenol. A dose-dependent increase in hydrogen peroxide, malondialdehyde, electrolyte leakage, and proline content was observed with Fedaleh EO or Treflan. However, a decline in cell viability, germination, radicle length, radicle weight, plumule length, plumule weight, and seedling vigor index was observed in a dose-dependent manner with Fedaleh EO or Treflan. The weight of the radicle and plumule was noticeably decreased by 27 %, 28 %, and 14 %, 19 % respectively when treated with essential oils derived from the stem and flower of the Fedaleh, as compared to Treflan. Interestingly, at concentrations of 5 μL/mL EO, the germination, radicle length, plumule length, and seedling vigor index significantly decreased by 64–72 %, 56-56 %, 41–44 % and 90–93 % % as compared with control, respectively. The essential oils extracted from different parts of Fedaleh showed no significant difference in terms of hydrogen peroxide, electrolyte leakage, cell viability, and proline content, compared to Treflan (P > 0.05). Compared to the control, Treflan did not affect germination (P > 0.05), but the EO of Fedaleh's different parts significantly inhibited germination (P < 0.05). The growth inhibitors at a concentration of ≥1 μL/mL significantly reduced the length of the radicle and plumule in Chenopodium album. Overall, Fedaleh EO has significant potential as a growth inhibitor and oxidative stress inducer to prevent weed interference. This makes it a suitable option for the commercial production of a natural herbicide.

In silico analysis of potential inhibitors for breast cancer targeting 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyses.

Breast cancer (BC) is still one of the major issues in world health, especially for women, which necessitates innovative therapeutic strategies. In this study, we investigated the efficacy of retinoic acid derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which plays a crucial role in the biosynthesis and metabolism of oestrogen and thereby influences the progression of BC and, the main objective of this investigation is to identify the possible drug candidate against BC through computational drug design approach including PASS prediction, molecular docking, ADMET profiling, molecular dynamics simulations (MD) and density functional theory (DFT) calculations. The result has reported that total eight derivatives with high binding affinity and promising pharmacokinetic properties among 115 derivatives. In particular, ligands 04 and 07 exhibited a higher binding affinity with values of -9.9 kcal/mol and -9.1 kcal/mol, respectively, than the standard drug epirubicin hydrochloride, which had a binding affinity of -8.2 kcal/mol. The stability of the ligand-protein complexes was further confirmed by MD simulations over a 100-ns trajectory, which included assessments of hydrogen bonds, root mean square deviation (RMSD), root mean square Fluctuation (RMSF), dynamic cross-correlation matric (DCCM) and principal component analysis. The study emphasizes the need for experimental validation to confirm the therapeutic utility of these compounds. This study enhances the computational search for new BC drugs and establishes a solid foundation for subsequent experimental and clinical research.

THE ANALYSIS STUDY OF EFFECTIVENESS AND SAFETY OF ORAL SILDENAFIL CITRATE FOR TREATMENT OF ERECTILE DYSFUNCTION : A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Erectile dysfunction (ED) is a medical condition affecting men's sexual performance and well-being. Sildenafil citrate, a specific inhibitor of phosphodiesterase type 5, is approved for treating ED. The efficacy and safety of oral sildenafil citrate in treating ED are crucial for successful treatment procedures. Understanding the relationship between the efficacy and safety of oral sildenafil citrate can help develop successful treatment procedures for ED patients. Methods: This systematic review adhered to the PRISMA 2020 guidelines and primarily examined entire English literature published between 2000 and 2024. Only editorials and review articles published in the same publication as the submission were accepted if they possessed a Digital Object Identifier (DOI). A variety of online platforms, including ScienceDirect, PubMed, and SagePub, were utilized to gather the relevant literature. Result: The study analyzed more than 2000 papers from reputable sources such as Science Direct, SagePub, and PubMed. After deciding to subject eight publications to additional inspection, a thorough evaluation of the entire body of literature was carried out. Conclusion: Sildenafil, a potent treatment for erectile dysfunction (ED), has been found to be effective in improving men's psychosocial aspects. It is an inhibitor of PDE5, a condition that affects men's emotional well-being. The study also found that the firmness of erections was linked to improvements in psychosocial aspects. Sildenafil can be used interchangeably with tablets, providing a convenient alternative for those with difficulty swallowing. However, follow-up for men with ED is often inadequate due to improper doses and lack of understanding.

Ferroptosis is involved in Staphylococcus aureus-induced mastitis through autophagy activation by endoplasmic reticulum stress

Cell death caused by severe Staphylococcus aureus (S. aureus) infection is a fatal threat to humans and animals. However, whether ferroptosis, an iron-dependent form of cell death, is involved in S. aureus-induced cell death and its role in S. aureus-induced diseases are unclear. Using a mouse mastitis model and mammary epithelial cells (MMECs), we investigated the role of ferroptosis in the pathogenesis of S. aureus infection. The results revealed that S. aureus-induced ferroptosis in vivo and in vitro as demonstrated by dose-dependent increases in cell death; the level of malondialdehyde (MDA), the final product of lipid peroxidation; and dose-dependent decrease the production of the antioxidant glutathione (GSH). Treatment with typical inhibitors of ferroptosis, including ferrostatin-1 (Fer-1) and deferiprone (DFO), significantly inhibited S. aureus-induced death in MMECs. Mechanistically, treatment with S. aureus activated the protein kinase RNA-like ER kinase (PERK)-eukaryotic initiation factor 2, α subunit (eIF2α)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) pathway, which subsequently upregulated autophagy and promoted S. aureus-induced ferroptosis. The activation of autophagy degraded ferritin, resulting in iron dysregulation and ferroptosis. In addition, we found that excessive reactive oxygen species (ROS) production induced ferroptosis and activated endoplasmic reticulum (ER) stress, manifesting as elevated p-PERK-p-eIF2α-ATF4-CHOP pathway protein levels. Collectively, our findings indicate that ferroptosis is involved in S. aureus-induced mastitis via ER stress-mediated autophagy activation, implying a potential strategy for the prevention of S. aureus-associated diseases by targeting ferroptosis. In conclusion, the ROS-ER stress-autophagy axis is involved in regulating S. aureus-induced ferroptosis in MMECs. These findings not only provide a new potential mechanism for mastitis induced by S. aureus but also provide a basis for the treatment of other ferroptotic-related diseases.

A cyanobacterial sigma factor F controls biofilm-promoting genes through intra- and intercellular pathways

Cyanobacteria frequently constitute integral components of microbial communities known as phototrophic biofilms, which are widespread in various environments. Moreover, assemblages of these organisms, which serve as an expression platform, simplify harvesting the biomass, thereby holding significant industrial relevance. Previous studies of the model cyanobacterium Synechococcus elongatus PCC 7942 revealed that its planktonic growth habit results from a biofilm-suppression mechanism that depends on an extracellular inhibitor, an observation that opens the door to investigating cyanobacterial intercellular communication. Here, we demonstrate that the RNA polymerase sigma factor SigF1, is required for this biofilm-suppression mechanism whereas the S. elongatus paralog SigF2 is not involved in biofilm regulation. Comprehensive transcriptome analyses identified distinct regulons under the control of each of these sigma factors. sigF1 inactivation substantially lowers transcription of genes that code for the primary pilus subunit and consequently prevents pilus assembly. Moreover, additional data demonstrate absence of the biofilm inhibitor from conditioned medium of the sigF1 mutant, further validating involvement of the pilus assembly complex in secretion of the biofilm inhibitor. Consequently, expression is significantly upregulated for the ebfG-operon that encodes matrix components and the genes that encode the corresponding secretion system, which are repressed by the biofilm inhibitor in the wild type. Thus, this study uncovers a basic regulatory component of cyanobacterial intercellular communication, a field that is in its infancy. Elevated expression of biofilm-promoting genes in a sigF1 mutant supports an additional layer of regulation by SigF1 that operates via an intracellular mechanism.

Microglia Involvement into Acute and Chronic Brain Damage in Diabetic Rats: Impact of GLP-1RA and SGLT-2i.

Acute and chronic brain damage in type 2 diabetes mellitus (DM) determines the need to investigate the neuroprotective potential of glucose-lowering drugs. The purpose was to directly compare the neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) with different duration of action and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetic rats with and without stroke. DM was modelled using high-fat diet and nicotinamide+streptozotocin protocol. The following groups (n = 15 each) were formed: DM without treatment, treatment with liraglutide, dulaglutide, canagliflozin as well as control group without DM and treatment. After 8 weeks, 10 rats from each group underwent middle cerebral artery occlusion. In the reperfusion period neurological deficit, neuroglial damage markers and brain necrosis were evaluated. Brain slices from the remaining 5 animals in each group were histologically examined for microglial activation and neuronal damage. Brain damage was similar in "DM" and "Control" (17.53 [14.23; 26.58] and 15.87 [13.40; 22.68] % of total brain volume, respectively). All study drugs diminished damage volume comparing with "DM" and "Control" whereas the necrosis volume in "DM+Liraglutide" was smaller than in "DM+Canagliflozin" and did not significantly differ from "DM+Dulaglutide" (2.9 [1.83; 4.71], 6.17 [3.88; 8.88] and 4.57 [3.27; 7.90] %). The neurological deficit was more prominent in "DM" than in "Control", while all the drugs demonstrated similar positive effect. Neurofilament light chains (NLC) did not differ between "DM" and "Control". Dulaglutide and canagliflozin caused a marked decrease in NLC. Protein S100BB level was similar in "DM" and "Control". Liraglutide caused the largest S100BB decrease, while canagliflozin did not influence it. In chronic brain ischaemia, all drugs increased the number of normal neurons, but GLP-1RAs had a more pronounced effect. DM was accompanied by increased number of activated microglial cells in Cornu Ammonis (CA)1 hippocampal region. Both GLP-1RAs reduced the number of Iba-1-positive cells, with dulaglutide being more effective than liraglutide, whereas canagliflozin did not affect this parameter. GLP-1RAs and SGLT-2i have neuroprotective properties against acute and chronic brain damage in diabetic rats, although the infarct-limiting effect of GLP-1RAs may be more pronounced. GLP-1RAs and SGLT-2i exert their protective effects by directly influencing neuronal survival, whereas GLP-1RAs also affect microglia.

Ameliorative effects of sildenafil against carbon tetrachloride induced hepatic fibrosis in rat model through downregulation of osteopontin gene expression

The liver carries out many essential tasks, such as synthesising cholesterol, controlling the body’s storage of glycogen, and detoxifying metabolites, in addition to performing, and regulating homeostasis. Hepatic fibrosis is a pathological state characterized by over accumulation of extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor of type 5 phosphodiesterase) has anti-inflammatory, antioxidant and anti-apoptotic properties. It is commonly used to treat erectile dysfunction in male. The purpose of the current investigation was to evaluate sildenafil’s hepatoprotective potential against liver fibrosis in rats that was caused by carbon tetrachloride (CCl4). Liver enzymes and oxidative markers as well as profibrotic genes were determined. The findings showed that sildenafil alleviates the hepatic dysfunctions caused by CCl4 by restoring normal levels of ALT, AST, and GGT as well as by restoring the antioxidant status demonstrated by increased glutathione (GSH), and catalase. In addition, a significantly down-regulated the mRNA expressions of profibrotic genes [collagen-1α, IL-1β, osteopontin (OPN), and transforming growth factor-β (TGF-β)]. Additionally, sildenafil lessens the periportal fibrosis between hepatic lobules, congestion and dilatation in the central vein, and the inflammatory cell infiltrations. As a result, it is hypothesized that sildenafil may be helpful in the management of hepatotoxicity brought on by CCl4 through suppressing OPN.

Exploring the Potential of Avenanthramides and their Analogues as α-Glucosidase Inhibitors for Type 2 Diabetes Treatment Utilizing Virtual Screening, Molecular Dynamics, and Drug-likeness Predictions

Exploring the Potential of Avenanthramides and their Analogues as α-Glucosidase Inhibitors for Type 2 Diabetes Treatment Utilizing Virtual Screening, Molecular Dynamics, and Drug-likeness Predictions

Accumulation and growth toxicity mechanisms of fluxapyroxad revealed by physiological, hepatopancreas transcriptome, and gut microbiome analysis in Pacific white shrimp (Litopenaeus vannamei)

Fluxapyroxad (FX), a typical succinate dehydrogenase inhibitor fungicide, is causing increased global concerns due to its fungicide effects. However, the accumulation and grow toxicity of FX to Litopenaeus vannamei (L. vannamei) is poorly understand. Therefore, the accumulation pattern of FX in L. vannamei was investigated for the first time in environmental concentrations. FX accumulated rapidly in shrimp muscle. Meanwhile, growth inhibition was observed and the mechanism derived by primarily accelerated glycolipid metabolism and reduced glycolipid content. Moreover, exposure to environmental concentrations of FX induced significant growth inhibition and oxidative stress and inhibited oxidative phosphorylation and TCA cycle in L. vannamei. The endocytosis signaling pathway genes were activated, thereby driving growth toxicity. Oxidative phosphorylation and cytosolic gene expression were further rescued in elimination experiments, demonstrating the mechanism of growth toxicity by FX exposure. The results revealed that FX persistently altered the gut microbiome of L. vannamei using gut microbiome sequencing, particularly with increased Garcinia Purple Pseudoalteromonas luteoviolacea for organic pollutant degradation. This study provided new insights into the potential toxicity of FX to marine organisms, emphasizing the need for further investigation and potential regulatory considerations.

Efficacy and safety of the combination or monotherapy with GLP-1 receptor agonists and SGLT-2 inhibitors in Type 2 diabetes mellitus: An update systematic review and meta-analysis

PurposeTo evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter2(SGLT-2) inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). MethodsTo construct an exhaustive database of randomized controlled trials (RCTs) concerning SGLT-2 inhibitors and GLP-1 agonists, a methodical search was undertaken across a range of databases, such as Embase, PubMed, and the Cochrane Central Register of Controlled Trials, from their inception to January 2023. Following this, a meta-analysis was executed to amalgamate the collected data, which allowed for the calculation of standardized mean differences (SMDs), odds ratios (ORs), and 95 % confidence intervals (CIs) for a spectrum of outcomes. This analytical approach was designed to yield a quantitative evaluation of the therapeutic efficacy and safety profile of SGLT-2 inhibitors and GLP-1 agonists for the treatment of diabetes mellitus. ResultsWhen compared to GLP-1 agonist therapy alone, the combination therapy did not significantly reduce fasting plasma glucose (FPG) levels (95 % confidence interval [CI]: -0.27, 0.10; p = 0.35), body weight (95 % CI: -0.18, 0.18; p = 1.00), Glycosylated Hemoglobin, Type A1C (HbA1c) (95 % CI: -0.29, 0.07; p = 0.22), or systolic blood pressure (SBP) values (95 % CI: -0.29, 0.06; p = 0.21). In contrast, when compared to SGLT-2 inhibitor therapy alone, combination therapy significantly decreased FPG by 0.24 mmol/L (95 % CI: -0.43, -0.05; p = 0.01), HbA1c by 0.45 % (95 % CI: -0.72, -0.18; p = 0.001), and SBP by 0.12 mmHg (95 % CI: -0.24, 0.00; p = 0.05). However, the combination therapy failed to demonstrate a significant reduction in body weight when compared with either SGLT-2 inhibitor therapy (95 % CI: -0.20, 0.05; p = 0.24) or GLP-1 agonist therapy (95 % CI: -0.18, 0.18; p = 1.00). Additionally, the combination therapy did not increase the incidence of hypoglycemia. It should be noted that data regarding mortality and cardiovascular outcomes were limited. ConclusionsThe combination treatment of SGLT-2 inhibitors and GLP-1 receptor agonists effectively reduces HbA1c, FPG, and SBP without elevating the risk of hypoglycemia when compared to monotherapy with SGLT-2 inhibitors. However, these beneficial effects were not observed when the combination therapy was compared with GLP-1 receptor agonist treatment alone.

The effects of aging time on the corrosion inhibition performance of KI and its synergistic effect with a typical phosphorus-based ionic liquid inhibitor

Potassium iodide (KI) is regarded as an ideal synergist for typical corrosion inhibitors. However, the synergistic effect of KI may be compromised due to its oxidation in acidic solutions. In this work, the anticorrosion performance of KI with different aging times in HCl solution and their synergistic effect with dodecyltriphenylphosphonium bromide (C12TPB) were evaluated via electrochemical tests and surface characterization techniques. The corrosion inhibition efficiency of KI gradually increased from 6.41 % to 38.99 % with increasing aging time to 6 h, while the synergy coefficient between KI and C12TPB abnormally decreased from greater than 1.0 to less than 0.4. UV–vis results and quantum chemical calculation demonstrated that the generated I3− during the aging process caused negative impact on the adsorption of C12TPB, leading to the reduced anticorrosion performance. This study provides valuable insights for the rational utilization of KI as the corrosion inhibitor and synergist.