Inhibition Capability Research Articles

Development of Tyrosine Phosphatase 1B Inhibitors Based on Molecular Docking, Kinetics, and Toxicity Studies

AbstractProtein Tyrosine Phosphatase 1B (PTP1B) is a protein that contributes to the development of diseases that affect millions of people worldwide. In the last five years, several studies have been carried out to develop a drug that is capable of inhibiting the functions of this protein that are related to chronic degenerative diseases and obesity. In this study, we used PTP1B as a therapeutic target to perform a molecular docking to identify compounds that specifically bind to the PTP1B human protein. After molecular docking from over 500,000 compounds, we selected the six with the highest binding score and evaluated their inhibitory effect in in vitro assays. The data showed that PT2 compound was the most potent with an IC50 value of 9 μM and a noncompetitive inhibition mechanism. According to molecular docking, this compound made specific interactions in the catalytic domain of PTP1B, that could be responsible for their inhibition capability. Furthermore, cytotoxic studies in MCF‐7 cells indicated that it could be safe for humans. Therefore, PT2 compound may be a promising new drug to attend the diseases where PTP1B has functions.

Differential plant cell responses to Acidovorax citrulli T3SS and T6SS reveal an effective strategy for controlling plant-associated pathogens.

Acidovorax citrulli is a gram-negative plant pathogen that employs the type Ⅲ secretion system (T3SS) to infect cucurbit crops and cause bacterial fruit blotch. This bacterium also possesses an active type Ⅵ secretion system (T6SS) with strong antibacterial and antifungal activities. However, how plant cells respond to these two secretion systems and whether there is any cross talk between T3SS and T6SS during infection remain unknown. Here, we employ transcriptomic analysis to compare cellular responses to the T3SS and the T6SS during in planta infection and report distinctive effects on multiple pathways. The T3SS-mediated differentially expressed genes were enriched in the pathways of phenylpropanoid biosynthesis, plant-pathogen interaction, MAPK signaling pathway, and glutathione metabolism, while the T6SS uniquely affected genes were related to photosynthesis. The T6SS does not contribute to the in planta virulence of A. citrulli but is critical for the survival of the bacterium when mixed with watermelon phyllosphere bacteria. In addition, T3SS-mediated virulence is independent of the T6SS, and the inactivation of the T3SS does not affect the T6SS-mediated competition against a diverse set of bacterial pathogens that commonly contaminate edible plants or directly infect plants. A T6SS-active T3SS-null mutant (Acav) could inhibit the growth of Xanthomonas oryzae pv. oryzae significantly both in vitro and in vivo and also reduce symptoms of rice bacterial blight. In conclusion, our data demonstrate the T6SS in A. citrulli is nonpathogenic to the plant host and can be harnessed as a pathogen killer against plant-associated bacteria. IMPORTANCE Chemical pesticides are widely used to protect crops from various pathogens. Still, their extensive use has led to severe consequences, including drug resistance and environmental contamination. Here, we show that an engineered T6SS-active, but avirulent mutant of Acidovorax citrulli has strong inhibition capabilities against several pathogenic bacteria, demonstrating an effective strategy that is an alternative to chemical pesticides for sustainable agricultural practices.

Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors

The drug treatment of Alzheimer's disease (AD) remains a significant scientific challenge, necessitating a continual search for new drug candidates. In this context, we present here, for the first time, new oxime-arylboronic acid hybrids (L1-L6) as potential anti-AD agents. These hybrids were synthesized and evaluated for their inhibitory capabilities on the activity of non-human cholinesterases [Electrophorus electricus Acetylcholinesterase (EeAChE) and Equine Butyrylcholinesterase (EqBChE)] as well as human cholinesterases [erythrocyte Acetylcholinesterase (hAChE) and plasma Butyrylcholinesterase (hBChE)]. We also assessed the safety of these compounds in a microglia cell line and analyzed the compound-enzyme interactions using molecular docking and molecular dynamics simulations. All compounds were found to be safe for the tests conducted. None of them exhibited significant inhibitory activity against hAChE or EeAChE. However, L1-L5 demonstrated inhibition of EqBChE and hBChE, with L3 being the most potent inhibitor of hBChE (IC50 = 6.41 ± 0.62 µM) and EqBChE (IC50 = 81.28 ± 4.01 µM). Additionally, L2, L3, and L5 showed 8–15 times higher potency as inhibitors of hBChE compared to EqBChE. These findings indicate that the hybrid oxime-arylboronic acids act as specific inhibitors of BChE, with a notable selectivity for hBChE, making them promising structures for the development of more potent and selective hBChE inhibitors.

Microfluidic Investigation of the Ion-Specific Effect on Bubble Coalescence in Salt Solutions.

A microfluidic method was developed to study the ion-specific effect on bubble coalescence in salt solutions. Compared with other reported methods, microfluidics provides a more direct and accurate means of measuring bubble coalescence in salt solutions. We analyzed the coalescence time and approach velocity between bubbles and used simulation to investigate the pressure evolution during the coalescence process. The coalescence time of the three salt solutions decreased initially and then increased as the concentration of the salt solution was increased. The concentration with the shortest coalescence time is considered as the transition concentration (TC) and exhibits ion-specific. At the TC, the change in coalescence time indicates a shift in the effect of salt on bubble coalescence from facilitation to initial inhibition. Meanwhile, it can be seen that the sodium halide solutions significantly inhibit the bubble coalescence and the inhibition capability follows the order NaCl > NaBr > NaI. The results of the approach velocity show that the coalescence time decreases with increasing approach velocity, as well as the approach velocity was strongly influenced by concentration. The approach velocity undergoes a significant change at the TC. Furthermore, simulations of bubble coalescence in the microchannel indicate that the vertical pressure gradient at the center point of the bubble pairs increases as bubbles approach, driving liquid film drainage until bubble coalescence. The pressure at the center of the bubble pair reaches the maximum when the bubbles have first coalesced. It was further revealed that the concentration of the salt solution has a significant impact on the maximum pressure, as evidenced by the observed trend of decreasing pressure values with increasing concentrations.

Characterization and genomic analysis of the vibrio phage R01 lytic to Vibrio parahaemolyticus

Vibrio parahaemolyticus is a significant zoonotic pathogen that is capable of causing infections in marine animals and contaminating seafood. In this study, we characterized a bacteriophage, vibrio phage R01, which exhibited lytic activity against V. parahaemolyticus VP-ABTNL, a strain known to cause skin ulceration in the juvenile sea cucumber. Morphological analysis revealed that vibrio phage R01 belongs to the Siphoviridae family of the Caudovirales order. A one-step growth curve analysis showed that the latent period and burst period of R01 were approximately 20 min, with a burst size of 316 PFU (plaque-forming unit) per infected cell. The stability determination assay showed that the lytic activity of phage R01 was optimal at 4–28 °C and a pH of 7.0, while it ceased at temperatures higher than 60 °C. The inhibition ability of the vibrio phage R01 against the VP-ABTNL was tested in vitro using the phage with three MOI (multiplicity of infection) values of 1, 10 and 100. All treated cultures exhibited a significant (P < 0.05) inhibition of VP-ABTNL growth compared to the untreated culture. Notably, the phage treated culture with a MOI of 100 displayed a consistently inhibition capability, comparable to the antibiotic-treated group (P > 0.05). Subsequently, the whole genome of the vibrio phage R01 was sequenced and analyzed. The genome of phage R01 consists of 75,514 bp with a G+C content of 49.42%. Twenty-four of the 75 putative proteins encoded by this phage have known functions, and no rRNA and tRNA genes were identified. Phylogenetic analysis based on DNA polymerase and terminase large subunit revealed that phage R01 is a new species within the genus of Mardecavirus. These findings indicate that the vibrio phage R01 may serve as a viable alternative agent for preventing V. parahaemolyticus infections.

Corrosion resistance improvement of mild steel in different pH using peel garlic green inhibitor

Corrosion resistance is the main drawback of mild steels, as AISI 1020. To decrease steel degradation, corrosion inhibitors are used and the green inhibitors gained relevance recently due to their low environment impact. Although extensively studied, the literature is mainly focused in the inhibitors use in acidic media. In this study, the aim was to investigate the efficiency of garlic peel as a green inhibitor in different aqueous solutions: acid (with HCl), neutral (with NaCl), and basic (with NaOH), in order to assess its inhibition capabilities across various pH levels. Mass loss and electrochemical corrosion tests demonstrated efficiency in all conditions tested. Additionally, SEM/EDS analysis was conducted to examine the reduction and alteration of corrosion products following the mass loss tests. In acidic media, the inhibitor's efficiency decreased with increasing exposure time, up to 24 h. Conversely, for neutral and basic media the inhibition efficiency increased up to 24 h. This increase was higher in the basic NaOH-containing solution. Quantum simulation further supported these findings, indicating that alliin and allicin, molecules found in garlic, generate more active specimens in basic conditions. This insight helps explain the superior performance observed in the NaOH solution.

Coordination-Driven Self-Assembly of Biomedicine to Enhance Photodynamic Therapy by Inhibiting Proteasome and Bcl-2.

Tumor cells resist oxidative damage and apoptosis by activating defense mechanisms. Herein, a self-delivery biomedicine (designated as BSC) is developed by the self-assembly of Bortezomib (BTZ), Sabutoclax (Sab) and Chlorin e6 (Ce6). Interestingly, BTZ can be coordinated with Sab to promote the assembly of uniform ternary biomedicine through non-covalent intermolecular interactions. Moreover, BTZ as a proteasome inhibitor can prevent tumor cells from scavenging damaged proteins to reduce their oxidative resistance. Sab can downregulate B-cell lymphoma 2 (Bcl-2) to decrease the antiapoptotic protein. Both the proteasome and Bcl-2 inhibitions contribute to increasing cell apoptosis and amplifying photodynamic therapy (PDT) efficacy of Ce6. Encouragingly, carrier-free BSC receives all biological activities of these assembly elements, including photodynamic performance as well as inhibitory capabilities of proteasome and Bcl-2. Besides, BSC has a preferable cellular uptake ability and tumor retention property, which increase the drug delivery efficiency and bioavailability. In vitro and in vivo research demonstrate the superior PDT efficiency of BSC by proteasome and Bcl-2 inhibitions. Of special note, the coordination-driven self-assembly of BSC is pH-responsive, which can be disassembled for controlled drug release upon tumor acidic microenvironment. This study will expand the applicability of self-delivery nanomedicine with sophisticated mechanisms for tumor treatment.

Facile synthesis of N-doped carbon dots (N-CDs) for effective corrosion inhibition of mild steel in 1 M HCl solution

N-CDs, as a novel and eco-friendly inhibitor, was synthesized easily by hydrothermal carbonization technique aiming to inhibit mild steel (MS) corrosion in 1 mol/L HCl. XRD, TEM, SEM, FTIR, UV-vis spectrophotometer and photoluminescence (PL) were utilized to characterize N-CDs. Potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) techniques along with the complementary surface studies were combined to investigate the corrosion inhibition capability of N-CDs for MS. N-CDs were found nanometer-sized (≈ 4 nm) with quasi-spherical morphology and high crystallinity. Inhibition efficiency, directly proportional to concentration but inversely with temperature, was measured as high as 96.73% (PDP) and 95.21% (EIS) at 200 mg/L. Inhibition mechanism refered mainly to adsorption process that good obeyed Langmuir adsorption isotherm. The surface studies, quantitatively verified by EDX, showed a smoother surface of MS in presence of the N-CDs. Furthermore, the UV-visible spectroscopy effectively revealed the complexations between iron and metal surfaces.

Hyparrhenia variabilis a potential invasive exotic weed at Mexico

The genus Hyparrhenia Andersson ex E.Fourn. is native to Africa, but presents in several countries and many parts of the world. Mexico is one of the countries, where Hyparrhenia rufa (Nees) Stapf (Poaceae) is found. However, it is classified as a highly invasive exotic species; therefore, is on the list of invasive species in Mexico. In recent years, the presence of Hyparrhenia cymbaria (L.) Stapfand and Hyparrhenia variabilis Stapf (Poacear) has been reported, while H. variabilis has been observed in the state at Morelos, Michoacán, and Jalisco. H. variabilis has been particularly identified in the municipality of Tepatitlan, Jalisco, Mexico. It has been observed that it grows densely and displaces native vegetation. Some studies mention that there are biotypes that have the ability to inhibit nitrogen-fixing bacteria, so it is necessary to study its biology and its inhibition capabilities around nitrogen fixation and seek strategies to stop its spread. The objective of this research was to review the information that exists on the species H. variabilis and its control. Apparently, there is a lack of information on this specie. However, there are some studies on other species of the genus such as H. rufa, which classified as highly invasive and some management reports can be used for H. variabilis. Therefore, it is necessary to develop management for the species based on literature available on H. rufa

Microbiome protection against Coccidioidesgrowth

Abstract During infection, the host utilizes multiple mechanisms to prevent colonization and dissemination. Protection begins at the surface, often via the commensal community found within our respiratory, skin, and intestinal tract. Microbiota disruption reduces the effectiveness of this protective barrier. Coccidioidomycosis, or Valley fever, is often misdiagnosed as community acquired bacterial pneumonia and treated with antibiotics that alter microbiota density and diversity. Commensal bacteria influence host immune responses to infection, and antibiotic treatment alters host immunity. A soil microbial antagonist related to Bacillus subtilis inhibits in vitro growth of Coccidioides through a clear zone of inhibition between fungi and bacteria. Whether host microbiota also inhibits Coccidioides is unknown. To assess if host microbiota has inhibition capabilities against Coccidioides, we performed two inhibition assays and measured Coccidioides growth area. A 50/50 inhibition assay was performed in which host microbiota and Coccidioides were placed in direct competition on agar plates. A spike in inhibition assay was performed where host microbiota was grown to 80% confluency, to mimic an established in vivo microbiome, before spiking in Coccidioides. Our data indicate that intestinal and respiratory host microbiome species inhibit Coccidioides growth. To assess if host microbiota depletion allows greater Coccidioides growth, in vitro antibiotic disc diffusion assays and in vivo treatments were performed. Our data suggests that host respiratory and intestinal commensals inhibit Coccidioides growth. Antibiotic treatment may kill protective host bacteria that creates a niche for Coccidioides invasion. Supported by grant VFR-19-633952 from University of California Office of the President.

Design, synthesis, and biological evaluation of novel dihydropteridone derivatives possessing oxadiazoles moiety as potent inhibitors of PLK1

Polo like kinase 1 (PLK1) is a serine/threonine kinase that is widely distributed in eukaryotic cells and plays an important role in multiple phases of the cell cycle. Its importance in tumorigenesis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of novel dihydropteridone derivatives (13a-13v and 21g-21l) possessing oxadiazoles moiety as potent inhibitors of PLK1. Compound 21g exhibited improved PLK1 inhibitory capability with an IC50 value of 0.45 nM and significant anti-proliferative activities against four tumor-derived cell lines (MCF-7 IC50 = 8.64 nM, HCT-116 IC50 = 26.0 nM, MDA-MB-231 IC50 = 14.8 nM and MV4-11 IC50 = 47.4 nM) with better pharmacokinetic characteristics than BI2536 in mice (AUC0-t = 11 227 ng h mL−1vs 556 ng h mL−1). Moreover, 21g exhibited moderate liver microsomal stability and excellent pharmacokinetic profile (AUC0-t = 11227 ng h mL−1, oral bioavailability of 77.4%) in Balb/c mice, acceptable PPB, improved PLK1 inhibitory selectivity, and no apparent toxicity was observed in the acute toxicity assay (20 mg/kg). Further investigation showed that 21 g could arrest HCT-116 cells in G2 phase and induce apoptosis in a dose-dependent manner. These results indicate that 21g is a promising PLK1 inhibitor.

Water-Soluble Cellulose As a New Class of Green CH4 Hydrate Inhibitors: Insights from Experiments and Molecular Dynamics Simulations

Cellulose is a cheap, ecofriendly, and abundant organic polymer. In this study, physically or chemically modified microcrystalline cellulose (MCC) was evaluated as a kinetic hydrate inhibitor (KHI) for CH4 hydrates using experimental and computational methods. To overcome the strong hydrophobicity of MCC, high-pressure homogenized cellulose (HPHC) was prepared by dispersing MCC homogeneously in water, and surface-modified ionic cellulose (SMIC) was obtained by attaching an ionic liquid (1,3-dimethylimidazolium methylphosphite, [DMIM][MP]) to the surface of MCC. The onset temperature and gas uptake of CH4 hydrates were experimentally measured to examine the inhibition performance of HPHC and SMIC. Experimental results demonstrated that both HPHC and SMIC functioned as potential KHIs and SMIC had better inhibition capability than HPHC. Molecular dynamics simulations were performed to reveal the inhibition mechanisms of the KHIs during cage formation and hydrate growth. It was found that the different inhibition effects of the KHIs were caused by a combination of multiple inhibition mechanisms, including both their interactions with water and cage adsorption. Given the improved hydrophilicity and inhibition performance through physical or chemical modification of the naturally derived organic compound, cellulose holds great potential as a novel and green KHI.

Antimicrobial, Antioxidant, Cytotoxic, DNA Protective Activities, and Molecular Docking Studies of the Methanolic Extract of Salvia siirtica Kahraman, Celep &amp; Dogan sp. Nov. (Lamiaceae)

Background: Medicinal plants have long been utilized in traditional medicine in Turkey and worldwide. The flora of Turkey is so rich it needs to be discovered, documented, and explored. This plant species is the origin of many valuable medicinal chemicals. Salvia species was used in folk medicine for many years in Turkey. One of the new Salvia species is Salvia siirtica. Methods: The antimicrobial, cytotoxic, antioxidant, DNA restriction inhibition, and DNA protective activities of methanolic extract of S. siirtica were studied. Results: The extract has better activity than the standard antibiotics against P. aeruginosa, meanwhile, showed high DPPH scavenging activity with an IC50 value of 28.72 ± 8.02 µg/ml. The extract exhibited good cytotoxic potential with IC50 value 0.31 ± 0.07 mg/ml towards H1299 cell line. The restriction enzyme inhibition in presence of plant extract proves that extract can interact with restriction endonuclease enzymes. Apigenin and Luteolin 7- glycoside are two high components of S. siirtica were docked against potential intracellular targets to evaluate their inhibition capability. Luteolin its derivative luteolin-7-glycoside showed the highest potential in molecular docking studies. Conclusions: Determining the bioactivity of these components by isolating them from the plant may pave the way for their use as supportive agents in the fight against many diseases.

Abstract 5842: Determining the tumor supportive and inhibitory capabilities of cancer associated fibroblast subpopulations in central nervous system metastasis

Abstract Central nervous metastases (CM) are surrounded by a complex tumor microenvironment (TME) comprised of a meshwork of extracellular matrix (ECM) proteins and an assemblage of cell types including cancer-associated fibroblasts (CAFs). We have previously shown that patient-derived CM CAFs can either support or inhibit tumor growth in vivo, suggesting that CM CAFs comprise a heterogenous subgroup of cells. Accordingly, we recently reported, based on literature in other cancer types, that CAFs can be categorized into four main subpopulations: ‘desmoplastic’, ‘immune’, ‘contractile’ and ‘aggressive’. The purpose of our study is to identify different CAF subpopulations in the TME of CM and determine their impact on CM growth. To do this, we performed single cell RNA sequencing (scRNA-seq) on 10 CM patient tissues and 8 patient-derived CM CAF cell lines established in our lab. ScRNA-seq analysis of tumor tissues revealed that desmoplastic, immune, contractile, and aggressive CAF subpopulations are also present in the TME of CM. In addition, scRNA-seq showed that CM CAF cell lines were mainly comprised of the desmoplastic and aggressive CAF subpopulations. These two subpopulations showed differential expression of the newly described tumor inhibitory CAF marker Immunoglobulin Superfamily Containing Leucine Rich Repeat (ISLR) and classic tumor supportive CAF marker Actin Alpha 2, Smooth Muscle (ACTA2, α-SMA), with desmoplastic CAFs showing ISLRhigh/α-SMAlow expression while aggressive CAFs were associated with ISLRlow/α-SMAhigh expression. Next, we used fluorescence activated cell sorting (FACS) based on the expression of ISLR on the cell surface to enrich and expand the ISLRhigh/α-SMAlow desmoplastic CAF and the ISLRlow/α-SMAhigh aggressive CM CAF subpopulations. Reciprocal expression of α-SMA and ISLR was confirmed by western blot and immunofluorescence after FACS. Additionally, co-culture experiments showed that ISLRhigh/α-SMAlow CM CAFs inhibit CM cell proliferation. In summary, our data show that there are several molecularly defined subpopulations of CAFs in the TME of CM that can act to either inhibit or promote CM tumor growth in vitro and in vivo. Our results support that the desmoplastic CM CAFs characterized by ISLRhigh/α-SMAlow can inhibit tumor growth. Overall, the present study improves our understanding of the CM TME, which ultimately will help establish new strategies to harness the cancer restraining capabilities of tumor inhibitory CAFs in order to improve outcomes for patients with CM. Citation Format: Thomas Simon, David N. Buckley, Gerald C. Gooden, Ben Y. Tew, Gabriel Zada, Bodour Salhia. Determining the tumor supportive and inhibitory capabilities of cancer associated fibroblast subpopulations in central nervous system metastasis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5842.

Pharmacological Targeting of Bcl-2 Induces Caspase 3-Mediated Cleavage of HDAC6 and Regulates the Autophagy Process in Colorectal Cancer

Compound 6d, a spiroindoline compound, exhibits antiproliferative capability against cancer cell lines. However, the exact underlying mechanism of this compound-mediated inhibitory capability remains unclear. Here, we showed that compound 6d is an inhibitor of Bcl-2, which suppresses CRC growth by inducing caspase 3-mediated intrinsic apoptosis of mitochondria. Regarding the underlying mechanism, we identified HDAC6 as a direct substrate for caspase 3, and caspase 3 activation induced by compound 6d directly cleaves HDAC6 into two fragments. Moreover, the cleavage site was located at D1088 in the DMAD-S motif HDAC6. Apoptosis stimulated by compound 6d promoted autophagy initiation by inhibiting interaction between Bcl-2 and Beclin 1, while it led to the accumulation of ubiquitinated proteins and the reduction of autophagic flux. Collectively, our findings reveal that the Bcl-2-caspase 3-HDAC6 cascade is a crucial regulatory pathway of autophagy and identify compound 6d as a novel lead compound for disrupting the balance between apoptosis and autophagy.

Lippia javanica leaf extract as an effective anti-corrosion agent against mild steel corrosion in 1 M HCl and its characterization by UHPLC/Q-TOF-MS spectroscopy and quantum chemical evaluation of its adsorption process on Fe(110)

A study was conducted to assess the anticorrosive potential of Lippia javanica leaf extract as a mild steel corrosion inhibitor in 1 M HCl acidic media. The chemical compositions of the acetone extract and its fractions were investigated by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) with C29H36O15 (verbascoside) identified as the major constituent of L. javanica. The anticorrosive assessment included weight loss measurements as well as an examination of thermodynamic parameters. According to weight loss data, 800 ppm of L. javanica at 303 K achieved a maximum inhibition efficiency of 98.01%. Temperature studies revealed that, in the presence of the extract, inhibition efficiency decreased, and activation energies increased as inhibitor concentration increased. The ability of L. javanica to maintain an inhibition efficiency of around 90% even at elevated temperatures, as supported by immersion time studies, indicates its effectiveness against mild steel corrosion. Electrochemical studies, open circuit potential (OCP), potentiodynamic polarization (PDP), and electrochemical impedance spectroscopy (EIS) were conducted to study the inhibition mechanism of the extract. PDP results indicated that the cathodic polarization slope values were higher than anodic ones, indicating that the extract components act principally on the cathodic branch of the metal, suppressing the reduction of hydrogen ions. Impedance diagrams showed that increasing L. javanica concentration increased charge transfer resistance (Rct) and decreased double layer capacitance (Cdl). The morphology and the surface composition of the mild steel were examined by scanning electron microscopy with energy dispersive x-ray analysis (SEM/EDX) to verify the presence of inhibitor components. Water contact angle (WCA), UV–visible, and Fourier-transform infrared spectroscopy (FTIR) were carried out to establish the corrosion-inhibitive properties responsible for the inhibition capabilities of the plant extract. Adsorption of L. javanica components onto mild steel surfaces was modelled to acceptable parameters using the Langmuir adsorption isotherm for PDP, EIS, and weight loss data. In this work, quantum calculations were performed to study the adsorption of the main component on a clean Fe(110) surface using density functional theory (DFT) with the PBE exchange-correlation functional in the DMol3 program.

Inhibitory Effects of Esculetin on Liver Cancer Through Triggering NCOA4 Pathway-Mediation Ferritinophagy in vivo and in vitro.

To explore the effects of Esculetin on liver cancer and explore potential mechanisms of Esculetin-inducing cells death. Esculetin's effects on the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells were detected by using CCK8, crystal violet staining, wound healing, TranswellTM and Annexin V-FITC/PI. Flow cytometry, fluorescence staining, Western blot, T-AOC, DPPH radical scavenging assay, hydroxyl radical's inhibitory capability and GSH test were used to examine the esculetin's effects on the ROS level, the oxidation-related substances and proteins' expression in hepatoma cells. In vivo experiment was performed by xenograft model. Ferrostatin-1 was used to determine the death way of hepatoma cells induced by esculetin. Live cell probe, Western blot, Fe2+ content, MDA, HE staining, Prussian blue staining and immunohistochemistry were used to examine the ferritinophagy-related phenomenon induced by esculetin in hepatoma cells. The relationship between esculetin and NCOA4-mediated ferritinophagy was confirmed through gene silence and overexpression, immunofluorescence staining and Western blot. Esculetin suppressed the proliferation, migration and apoptosis of HUH7 and HCCLM3 cells significantly, influenced the oxidative stress level, altered the autophagy and iron metabolism levels in cells, and produced a ferritinophagy-related phenomena. Esculetin increased the levels of cellular lipid peroxidation and reactive oxygen species. In vivo, esculetin could decrease tumour volume, promote LC3 and NCOA4 expressions, suppresse hydroxyl radical's inhibiting capacity and GSH, increase Fe2+ and MDA levels, decrease antioxidant proteins expression in tumour tissue. In addition, Esculetin could also increase the iron deposition of tumour tissues, promote ferritinophagy, and induce tumours' ferroptosis. Esculetin has an inhibitory effect on liver cancer in vivo and in vitro through triggering NCOA4 pathway-mediation ferritinophagy.

Pore pressure transmission test as measure of shale inhibition performance of nanoparticle additives in water based drilling fluids – A comprehensive review

This paper presents comprehensive review of effect of different nanoparticles such as nanosilica, aluminium nanoparticles (NPs), Magnesium oxide NPs, Zinc oxide NPs, Calcium carbonate NPs, Laponite NPs on pore pressure transmission and discusses its inhibition capability in different shale formations. Shale formations consist of water sensitive clays that react with water and swell. Fluid from water-based drilling fluid (WBDF) invades into shale sections and increases the pore pressure. Therefore, abnormal pore pressure is result of swelling mechanisms of clay that leads to wellbore instability. Pore pressure transmission test (PPT) measures membrane efficiency of shale formations in the oil and gas well drilling operation. Recently, it was reported that addition of nanoparticles in WBDF can plug the shale pores and decrease rate of PPT effectively up to 97%. However, the plugging ability of nanoparticles depends on its size, other additives in the drilling fluid and clay minerals in shale formation etc. This article also analyses nanoparticles performance with conventional shale inhibitors like polymers and clays.

An Update on Kidney Stones: Types, Mechanism and Treatment Approaches

Kidney stone illness is becoming more common and new studies shows that stones can be linked to a number of significant complications. Renal stone disorder is a condition of crystal concretion that forms in the kidney. It is a growing urological health problem that affects approximately 12% of the global population. Stone generation is a sophisticated process that includes a number of physicochemical phenomena, such as supersaturation of urine, nucleation, growth of crystal, crystal aggregation and retention of urinary stone. An imbalance between substances that induce or inhibit urine crystallisation controls these stages. These facts show stone therapy and stone prevention. There is many misunderstanding regarding how to handle stones among both the general public and clinicians. As a result, review is to consolidate up-to-date knowledge on kidney stone origin, pathophysiology, and management strategies of each kind of kidney stone. The phytochemicals present in the extract contribute to the plant's antiurolithiatic abilities. Several kinds of phytochemicals such as Flavonoids, Polysaccharide, Saponin etc have a favourable effect in the antiurolithiatic impact against kidney crystals, or in terms of dissolving or inhibitory capabilities. However, there is a limited knowledge on nutritional and medicinal treatments for lithiasis and prevention.

Conductive hydrogels with hierarchical biofilm inhibition capability accelerate diabetic ulcer healing

Diabetic ulcers (DUs) are characterized by massive biofilm formation, long-term inflammatory infiltration, and difficulty in healing. Electrical stimulation (ES) applied through hydrogel dressings is promising to treat DUs, but the development of advanced hydrogels with stable conductivity and effective antibacterial properties remains challenging. Loading antibiotics in hydrogels by absorption is prone to the initial burst release, which is associated with frequent dressing changes and bacterial resistance development. Herein, antibacterial terbium ions are incorporated into the hydrogel network by coordination interactions for sustainable release. Agarose and zwitterions are used to prevent protein absorption and bacterial adhesion due to their strong hydration ability. The combination of the antifouling components and bactericidal terbium ions in the hydrogel results in a tremendous antibacterial effect, which completely inhibits biofilm formation by Staphylococcus aureus and Escherichia coli. Polypyrrole is also covalently grafted to the hydrogel network, providing stable and biomimetic conductivity. When ES is applied through the hydrogel, the antibacterial hydrogel controls the inflammation induced by infection and the applied ES helps DUs pass the proliferation stage, and thus accelerates wound healing.