Modulation Of Resistance Research Articles

Comparative antibacterial activity of clove extract against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen belonging to the γ-proteobacteria family, known to cause pneumonia linked with ventilator use and nosocomial infections. With the increasing prevalence of antibiotic-resistant bacteria, there is a pressing need to identify alternatives to conventional antibiotics. Plant-derived substances (PDSs) offer potential not only as antibacterial agents but also as modulators of antibiotic resistance. In this study, diffusion assay using disc agar, and the minimum inhibitory concentration (MIC) assay of each imipenem, amoxicillin-clavulanic acid, and clove extract was determined. The clove extract was analyzed via the UHPLC/MS, and the checkerboard assay was employed to evaluate the potential synergistic effects of combining clove extract with both antibiotics. The combination of clove extract to each antibiotic led to a significant reduction in their respective MICs. Moreover, each antibiotic exhibited synergistic effects on the fractional inhibitory concentration value (FIC) of clove extract. The analysis identified seventeen components in the clove extract, predominantly flavonoids and phenolic compounds. The antibacterial efficacy of the Syzygium aromaticum Myrtaceae extract against P. aeruginosa indicated its potential as a promising antibacterial agent capable of enhancing the effectiveness of existing medications.

Stabilization of oxygen vacancy ordering and electrochemical-proton-insertion-and-extraction-induced large resistance modulation in strontium iron cobalt oxides Sr(Fe,Co)Oy

Electrochemically inserting and extracting hydrogen into and from solids are promising ways to explore materials’ phases and properties. However, it is still challenging to identify the structural factors that promote hydrogen insertion and extraction and to develop materials whose functional properties can be largely modulated by inserting and extracting hydrogen through solid-state reactions at room temperature. In this study, guided by theoretical calculations on the energies of oxygen reduction and hydrogen insertion reactions with oxygen-deficient perovskite oxides, we demonstrated that the oxygen vacancy ordering in Sr(Fe1−xCox)Oy (SFCO) epitaxial films can be stabilized by increasing the Co content (x ≥ 0.3) and revealed that it plays a key role in promoting proton accommodation into the SFCO lattice. We also show that the electrical resistance of SFCO films can be reversibly modulated by electrochemical proton insertion and extraction, and the modulation exceeds three orders of magnitude for Sr(Fe0.5Co0.5)O2.5 epitaxial films. Our results provide guidelines for controlling material properties through the insertion and extraction of hydrogen and for designing and exploring hydrogen-insertion materials.

Resistive switching and magnetism modulation of HfOx based memory with Co interlayer

Resistive switching and magnetism modulation of HfOx based memory with Co interlayer

Surface Defect Generation on SnO2 Nanoparticles Using High-Energy Ball Milling for H2S Gas Sensor Applications

Hydrogen sulfide (H2S) is a highly toxic and dangerous gas with a flammable and corrosive nature, making the development of reliable gas sensors for its detection vital. This study investigated the enhancement in H2S gas sensing performance of commercial SnO2 powders after high-energy milling. SnO2 powders were subjected to high-energy milling for 30, 60, and 90 min and then were characterized using advanced techniques to evaluate their morphology, chemical composition, and crystallinity. The response of a pristine SnO2 gas sensor, and ones where the SnO2 was milled for 30, 60 and 90 min, were 2.46, 2.27, 3.01, and 1.98, respectively, to 10 ppm H2S at 300°C. Thus, the H2S gas sensing results revealed that the SnO2 powders milled for 60 min exhibited the highest sensing performance. This improvement in H2S sensing performance was attributable to the reduced particle sizes achieved through the high-energy milling process, which increased the surface area and created defects on the surface of the SnO2 particles, thereby enhancing the interaction between the gas molecules and sensor material. The smaller morphological size of the particles and surface defects subsequently promoted the resistance modulation crucial for H2S gas detection. This study demonstrates that high-energy ball milling can effectively boost the gas-sensing features of SnO2 powders. The findings can provide guidance for enhancing the gas-sensing capabilities of other resistive sensors.

Efficacy of colistin-based combinations against pandrug-resistant whole-genome-sequenced Klebsiella pneumoniae isolated from hospitalized patients in Egypt: an in vitro/vivo comparative study

BackgroundColistin resistance significantly constrains available treatment options and results in the emergence of pandrug-resistant (PDR) strains. Treating PDR infections is a major public health issue. A promising solution lies in using colistin-based combinations. Despite the availability of in vitro data evaluating these combinations, the in vivo studies remain limited.ResultsThirty colistin-resistant Klebsiella pneumoniae (ColRKp) isolates were collected from hospitalized patients. Colistin resistance was detected using broth microdilution, and antimicrobial susceptibility was tested using the Kirby-Bauer method against 18 antibiotics. Extremely high resistance levels were detected, with 17% of the isolates being PDR. Virulence profiling, assessed using Anthony capsule staining, the string test, and the crystal violet assay, indicated the predominance of non-biofilm formers and non-hypermucoid strains. The isolates were screened for mcr genes using polymerase chain reaction. Whole-genome sequencing (WGS) and bioinformatics analysis were performed to characterize the genomes of PDR isolates. No plasmid-borne mcr genes were detected, and WGS analysis revealed that PDR isolates belonged to the high-risk clones: ST14 (n = 1), ST147 (n = 2), and ST383 (n = 2). They carried genes encoding extended-spectrum β-lactamases and carbapenemases, blaCTX-M-15 and blaNDM-5, on conjugative IncHI1B/IncFIB plasmids, illustrating the convergence of virulence and resistance genes. The most common mechanism of colistin resistance involved alterations in mgrB. Furthermore, deleterious amino acid substitutions were also detected within PhoQ, PmrC, CrrB, ArnB, and ArnT. Seven colistin-containing combinations were compared using the checkerboard experiment. Synergy was observed when combining colistin with tigecycline, doxycycline, levofloxacin, ciprofloxacin, sulfamethoxazole/trimethoprim, imipenem, or meropenem. The efficacy of colistin combined with either doxycycline or levofloxacin was assessed in vitro using a resistance modulation assay, and in vivo, using a murine infection model. In vitro, doxycycline and levofloxacin reversed colistin resistance in 80% and 73.3% of the population, respectively. In vivo, the colistin + doxycycline combination demonstrated superiority over colistin + levofloxacin, rescuing 80% of infected animals, and reducing bacterial bioburden in the liver and kidneys while preserving nearly intact lung histology.ConclusionsThis study represents the first comparative in vitro and in vivo investigation of the efficacy of colistin + doxycycline and colistin + levofloxacin combinations in clinical PDR ColRKp isolates characterized at a genomic level.

GSTA1/CTNNB1 axis facilitates sorafenib resistance via suppressing ferroptosis in hepatocellular carcinoma

The emergence of sorafenib resistance has become a predominant impediment and formidable dilemma in the therapeutic approach for hepatocellular carcinoma (HCC). Although the approval of next-generation drugs as alternatives to sorafenib is a significant development, the concurrent use of inhibitors that target additional key molecular pathways remains an effective strategy to mitigate the acquisition of resistance. Here, we identified Glutathione S-Transferase Alpha 1 (GSTA1) as a critical modulator of sorafenib resistance (SR) in hepatocellular carcinoma (HCC) based on our findings from experiments conducted on recurrent liver cancer tissues, xenograft mouse models, organoids, and sorafenib-resistant cells. Elevated GSTA1 levels are strongly associated with adverse clinical prognoses. The knockout of GSTA1 reinstates sorafenib sensitivity, whereas its overexpression attenuates drug efficacy. Mechanistically, GSTA1 enhances the accumulation of lipid peroxides and suppresses ferroptosis by exerting its peroxidase function to regulate the SR. Notably, the upregulation of GSTA1 expression is mediated by the transcription factor CTNNB1 (β-catenin), resulting in the formation of a cytoplasmic complex between GSTA1 and CTNNB1. This complex facilitates the nuclear translocation of CTNNB1, establishing a positive feedback loop. The combined use of GSTA1 and CTNNB1 inhibitors demonstrated synergistic anti-tumour effects through the induction of ferroptosis both in vitro and in vivo. Our findings reveal a novel regulatory role of the GSTA1/CTNNB1 axis in ferroptosis, suggesting that targeting GSTA1 and CTNNB1 could be a promising strategy to circumvent sorafenib resistance in HCC.

A small area-occupation three-stage OTA with transistor resistance and parasitic capacitance Q-factor modulation for miniaturized communication systems

A small area-occupation, three-stage operational transconductance amplifier (OTA) is proposed for miniaturized communication systems. Our work presents a novel RC impedance attenuation solution composed of transistor resistance and parasitic capacitance mainly modulating the Q-factor (TRPCQM) of complex poles and precisely handles the first zero and the second pole to enlarge unity-gain frequency (UGF). By employing source-drain transconductance equivalent resistance and inexpensive parasitic capacitance in our RC impedance attenuation block, the complex poles can be regulated meanwhile decreasing chip area occupation. Under a supply voltage of 1.2V, the proposed design is validated using a standard 0.18 μm CMOS process, occupying an ultra-small area of 0.00276 mm2. When driving an ultra-large load of over 20 nF, the design achieves a DC gain exceeding 110 dB and a unity-gain frequency (UGF) of more than 2.1 MHz, with a power consumption of only 10.46 μW.

Stretch-induced tunability of electrical transport properties of three-dimensional graphene-based foam structures

The fast electron transport and superior multidirectional flexibility of three-dimensional graphene-based foams (GFs) are pivotal in the realm of stretchable electronics. We observed pre-stretching induced modulation of the temperature-dependent electrical resistivity of GFs, where, as the pre-stretch strain level increased, the distinct temperature dependence of the resistivity of a GF sample would change and might even exhibit a notable transition from negative dependence to positive dependence. We attempted to interpret the phenomenon by proposing a new conduction network model that represents GF structures as interconnected polycrystalline graphene islands and island/island conduction junctions and incorporates three conduction mechanisms: thermally activated conduction across grain boundaries and phonon-limited conduction avoiding grain boundaries within a graphene island, and fluctuation-induced tunneling conduction across island/island conduction junctions. By fitting-assisted analysis, we found that the temperature dependence of the resistivity of a GF sample primarily relies on the discrete quantities of graphene islands and island/island conduction junctions, and the resistivity originating from each conduction mechanism. As pre-stretch strain level increases, these factors would change due to conduction network alteration, local strain-induced phonon hardening, and local strain-induced transport gap modulation, all resulting from pre-stretching. Our results offer valuable insights into the optimization of GFs-based stretchable electronic devices, such as performance enhancement through structural modifications.

Design, synthesis and biological evaluation of biaryl amide derivatives as modulators of multi-drug resistance

The emergence of multi-drug resistance (MDR) presents a significant impediment to the efficacy of cancer treatment. Aberrant expression of ABC (ATP-binding cassette) transporters is acknowledged as one of the underlying factors contributing to MDR. P-glycoprotein (P-gp, MDR1, ABCB1), breast cancer resistance protein (BCRP, ABCG2), and MDR-associated protein 1 (MRP1, ABCC1) are members of the ABC transporter, and their over-expression usually occurs in drug-resistant tumor cells. In this work, the structure-activity relationships of the biaryl amide skeleton were systematically investigated via structural optimization step by step, which led to the identification of an exceptionally potent resistance reversal agent, D2. Compound D2 effectively reversed MDR to paclitaxel and cisplatin in A2780/T, A2780/CDDP and A549/T cell lines. It could directly bind to P-gp and downregulate the expression of both P-gp and MRP1. The treatment with D2 increased the intracellular accumulation of Rh123 and inhibited P-gp-mediated drug efflux of Rh123 in A2780/T cells. Therefore, compound D2 exhibits promising potential in overcoming multidrug resistance (MDR) induced by P-gp in cancer.

(Keynote) Group-IV Epitaxy and Process Solutions for Stacked Gate-All-Around Nanosheet Technology Performance Improvement

Stacked gate-all-around (GAA) nanosheet (NS) devices are attractive candidates to replace FinFETs at the 3nm technology node and beyond due to their excellent electrostatic properties and scalability. GAA NS technology has multiple advantages compared to FinFET technology. GAA NS device with stacked nanosheets offers increased drive current compared to FinFET technology due to significant improvement in the total effective width per active footprint GAA NS device also enables gate length scaling thanks to its outstanding electrostatics and short channel control. Unlike FinFET, the active footprint is not quantized on NS. Therefore, flexible power/performance tuning can be achieved with variable nanosheet width. The industry agrees that GAA NS structure is the architecture of choice for the next device structure after FinFET as scaling continues. In fact, mass manufacturing for stacked GAA Nanosheet technology started and is currently offered as first-generation product at the 3nm technology node.Fabricating GAA NS structure can take advantage of many of the FinFET process integrations by adding elemental technology modules unique to the GAA NS structure. A specific SiGe/Si multi-layer epitaxy is employed for stacking Si NS channels. The SiGe layer is used as a sacrificial layer for forming inner spacer (IS) and defining the suspension thickness, the distance separating two consecutive stacked Si NS channels. The uniformity and crystallinity for the epitaxial SiGe/Si layers within wafer is critical since it will determine the Si NS channel thickness and performance. Abrupt Ge profile at the SiGe/Si interface is also required for achieving selective SiGe removal to form optimal IS profile and suppress Si NS channel surface roughness post channel release. IS is necessary to isolate the gate and S/D, playing an important role as a physical barrier to prevent S/D damage during channel release while providing device benefits. The IS profile and thickness are important for tuning device performance by modulation of capacitance and resistance. S/D epitaxial growth becomes more difficult as devices are scaled with a reduction of the opening of the S/D region For a GAA NS structure employing IS, all the focus will be on improving the integration and process to avoid negatively impacting the subsequent S/D epitaxial growth.PFET device performance degradation is expected due to modulation of hole mobility. Transitioning the device structure from FinFET to GAA NS dramatically changes the transport properties as the channel surface orientation changes and is more dominated by the (110) surface compared to (001) plane for a FinFET. Therefore, exploring performance improvement techniques is required for next generation GAA CMOS technologies in order to improve the pFET device. Increasing channel carrier mobility is one way to improve device performance. Hole mobility can be increased by inducing compressive stress into the channel material. SiGe is one of the most promising materials for pFET channel as strained SiGe channel FinFET device shows intrinsic mobility gain compared to Si channel FinFET. Additional SiGe channel benefits include Vt tunability and superior NBTI performance. As such, applying SiGe channel into GAA NS device has great potential for further improving pFET device performance. SiGe cladded NS channel formation through selective SiGe epitaxial growth post Si channel release is an effective method for maintaining strain in the SiGe region. The lattice constant difference between the epitaxial SiGe layer and Si channel NS results in compressive strain in the SiGe cladded layer. This technique maintains the compressive strain since there is no patterning step in the downstream process. Altering the channel orientation is another technique for modulating carrier mobility independent of internal and external stressor elements. For instance, hole mobility is higher for (110) planes than for (001) planes. The same process integration can be utilized for both substrate types for fabricating GAA Si channel NS devices on (001) and (110) bulk substrates, although careful engineering is required for SiGe/Si epitaxy on (110) substrate.In this talk, we will review the epitaxy processes and related technologies for GAA NS device fabrication. In addition, performance enhancement techniques such as, (1) strained SiGe channel and (2) channel surface orientation with high hole mobility, that can be applied for GAA NS pFET device are discussed.

Impact of a free normal velocity boundary on the modelling of external MHD modes

Free normal-flow (NF) conditions at the plasma boundary are shown to be essential for three-dimensional magnetohydrodynamic (MHD) simulations to agree with linear stability theory. A comparative verification study is presented between two different formulations of the boundary conditions (BCs) for velocity perturbations: (i) fully consistent free NF implementation and (ii) fixed NF formulation, neglecting flow perturbations at the numerical boundary. Numerical results are compared with consolidated figures of merit from the linear theory of external kink modes. We consider two classes of initial equilibria presenting different numerical challenges: a uniform current channel surrounded by pure vacuum and a shaped Wesson-like equilibrium, with smooth (polynomial) radial dependency. Only the fully consistent free NF formulation is invariably accurate in modelling the plasma interface at the numerical boundary, without the need of enforcing a pseudovacuum region at the edge of the simulation domain, as in most analogous past studies. This study employs the cylindrical code SPECYL (Cappello & Biskamp, Nucl. Fusion, vol. 36, no. 5, 1996, p. 571) that solves a full-MHD model without pressure gradients, whose fully consistent resistive wall module with free NF BCs was recently successfully verified against the independent code PIXIE3D (Spinicci et al., AIP Adv., vol. 13, no. 9, 2023, p. 095111).

Enhancing DOX efficacy against NSCLC through UDCA-mediated modulation of the TGF-β/MAPK autophagy pathways

Lung carcinoma, predominantly manifested as non-small cell lung cancer (NSCLC), significantly contributes to oncological mortality, underscoring an imperative for novel therapeutic paradigms. Amidst this context, the present investigation delineates the synergistic potentiation of doxorubicin (DOX)—a canonical chemotherapeutic—by Ursodeoxycholic acid (UDCA), a compound with a historical pedigree in hepatobiliary medicine, now repositioned within oncological pharmacotherapy due to its dichotomous cellular modulation—affording cytoprotection to non-malignant epithelia whilst eliciting apoptotic cascades in neoplastic counterparts. This study, through a rigorous methodological framework, elucidates UDCA’s capacity to inhibit NSCLC cellular proliferation and induce apoptosis, thereby significantly amplifying DOX’s chemotherapeutic efficacy. Notably, the co-administration of UDCA and DOX was observed to attenuate DOX-induced autophagy via the modulation of the TGF-β/MAPK signaling axis, a pathway pivotal in mediating cellular survival and autophagic mechanisms. Such findings not only underscore the therapeutic potential of UDCA as a chemosensitizer but also illuminate the molecular underpinnings of its modulatory effects, thereby contributing to the corpus of knowledge necessary to surmount chemoresistance in NSCLC. The implications of this research are twofold: firstly, it offers a compelling evidence base for the clinical reevaluation of UDCA in combinatory chemotherapeutic regimens; secondly, it posits a novel mechanistic insight into the modulation of chemotherapeutic efficacy and resistance. Collectively, these insights advocate for the expedited clinical translation of UDCA-DOX synergy, potentially heralding a paradigm shift in the management of NSCLC, thereby addressing a critical lacuna in contemporary oncological therapy.

Effect of nanoemulsion loaded with macela (Achyrocline satureioides) on the ultrastructure of Staphylococcus aureus and the modulating activity of antibiotics

Nanoformulations with herbal actives for treating bovine mastitis present an alternative for controlling bacterial infections in the emerging scenario of antimicrobial resistance. In this study, we investigated macela (Achyrocline satureioides) nanoemulsion (NE-ML), a formulation developed for the treatment of bovine mastitis (registered under Brazilian patent application BR 10 2021 008630 0), in the context of its bactericidal mechanism(s) of action and potential synergism with commercial antimicrobials. The effect of NE-ML on the integrity and cell permeability of Staphylococcus aureus was evaluated by measuring the electrical conductivity of bacterial suspensions exposed to different concentrations of NE-ML and by assessing the release of cellular constituents. Damage to bacterial ultrastructures was analyzed by transmission electron micrographs. The synergism of NE-ML with beta-lactam antibiotics and aminoglycosides was evaluated by the checkerboard test method against S. aureus (n = 6). The relative electrical conductivity of the bacterial solution gradually increased over time, reaching high values after exposure to 1xMIC (52.3%) and 2xMIC (75.34%) of NE-ML. Total proteins were detected in the bacterial suspensions exposed to NE-ML, increasing in concentration over exposure time (p < 0.05). Through bacterial micrographs, we observed that exposure to NE-ML (1xMIC) affected the integrity of the plasma membrane with invaginations in the cytosolic region and alterations in the cell wall. The increase in NE-ML concentration resulted in greater damage to the ultrastructure of S. aureus with changes in bacterial cell division patterns. When NE-ML was combined with the beta-lactam antimicrobials, the interaction was indifferent, indicating no modulation of antimicrobial resistance. In contrast, when combined with the aminoglycoside, a synergistic interaction did occur. These general findings suggest that the bactericidal action of NE-ML begins in the plasma membrane, causing alterations in its permeability and integrity, and extends to the cell wall, cytoplasm, and cell division. Although synergy was restricted to the aminoglycoside by destabilizing the bacterial cell membrane, this suggests that NE-ML can induce the entry of other actives, potentially reducing their therapeutic doses. Understanding the mechanism of action of this new nanoformulation is certain to drive pharmacological advances, broaden the perspective of its in vivo use, and improve the treatment of bovine mastitis.

Hyaluronic acid-functionalized ruthenium photothermal nanoenzyme for enhancing osteosarcoma chemotherapy: Cascade targeting and bidirectional modulation of drug resistance

Insufficient drug delivery efficiency in vivo and robust drug resistance are two major factors to induce suboptimal efficacy in chemotherapy of osteosarcoma (OS). To address these challenges, we developed polysaccharide hyaluronic acid (HA)-functionalized ruthenium nanoaggregates (Ru NAs) to enhance the chemotherapy of doxorubicin (DOX) for OS. These NAs, comprising Ru nanoparticles (NPs) and alendronate-modified HA (HA-ALN), effectively load DOX, resulting in DOX@Ru-HA-ALN NAs. The combination of HA and ALN in NAs ensures outstanding cascade targeting towards tumor-invaded bone tissues and CD44-overexpressing tumor cells, maximizing therapeutic efficacy while minimizing off-target effects. Concurrently, the Ru NPs in NAs function as “smart” photoenzymatic agent to not only in situ relieve hypoxia of OS via the catalysis of overexpressed H2O2 to produce O2, but also generate mild photothermal effect under 808-nm laser irradiation. They can bidirectionally overcome drug resistance of DOX via downregulation of resistance-related factors including multi-drug resistant associate protein, P-glycoprotein, heat shock factor 1, etc. The integration of cascade targeting with bidirectional modulation of drug resistance positions Ru-HA-ALN NAs to substantially enhance DOX chemotherapy for OS. Therefore, the present work highlights the potential of polysaccharide-functionalized nanomaterials in advancing tumor chemotherapy by addressing challenges of both delivery efficiency and drug resistance.

Chemical Profile, Antioxidant and Antimicrobial Activity of Marine Sponge Species Combined with Multivariate Statistical Analyses: Desmapsamma anchorata, Dysidea etheria and Echinodictyum dendroides.

Marine sponges are valuable sources of bioactive compounds, which have attracted pharmacological interest. This study aimed to evaluate the chemical profile, antioxidant, and antibacterial activities of the species Desmapsamma anchorata, Dysidea etheria, and Echinodictyum dendroides. The chemical profile involved identifying and quantifying polyphenols, and antioxidant activity was evaluated using various methods. The antibacterial and modulatory activities were evaluated using microdilution against pathogenic strains. The extracts contained a low amount of polyphenols. In the antioxidant assays, the EACDa and EMDa extracts exhibited better inhibitory results. In the antibacterial evaluation, extracts presented MIC ≥1024 μg mL-1. The modulation of the extracts combined with antibiotics showed significant effects against the multiresistant bacterium Pseudomonas aeruginosa. This study contributes to the deepening of chemical and biological knowledge of sponge species. It indicates that their extracts can act as good modulators of bacterial resistance to aminoglycoside antibiotics, which requires further investigation into their mechanisms of action.

Incretin-Based Therapies: A Promising Approach for Modulating Oxidative Stress and Insulin Resistance in Sarcopenia.

Recent studies have linked sarcopenia development to the hallmarks of diabetes, oxidative stress, and insulin resistance. The anti-oxidant and insulin sensitivityenhancing effects of incretin-based therapies may provide a promising option for the treatment of sarcopenia. This review aimed to unveil the role of oxidative stress and insulin resistance in the pathogenesis of sarcopenia and explore the potential benefits of incretin-based therapies in individuals with sarcopenia. PubMed, the Cochrane Library, and Google Scholar databases were searched by applying keywords relevant to the main topic, to identify articles that met our selection criteria. Incretin-based therapies manifested anti-oxidant effects by increasing the anti-oxidant defense system and decreasing free radical generation or by indirectly minimizing glucotoxicity, which was mainly achieved by improving insulin signaling and glucose homeostasis. Likewise, these drugs exhibit insulin-sensitizing activities by increasing insulin secretion, transduction, and β-cell function or by reducing inflammation and lipotoxicity. Incretin-based therapies, as modulators of oxidation and insulin resistance, may target the main pathophysiological factors of sarcopenia, thus providing a promising strategy for the treatment of this disease.

Autocrine Motility Factor and Its Peptide Derivative Inhibit Triple-Negative Breast Cancer by Regulating Wound Repair, Survival, and Drug Efflux.

Triple-negative breast cancer (TNBC) presents a significant challenge in oncology due to its aggressive nature and limited targeted therapeutic options. This study explores the potential of autocrine motility factor (AMF) and an AMF-derived peptide as novel treatments for TNBC. AMF, primarily secreted by neoplastic cells, plays a crucial role in cancer cell motility, metastasis, and proliferation. The research demonstrates that AMF and its derived peptide inhibit TNBC cell proliferation by modulating cellular migration, redox homeostasis, apoptotic pathways, and drug efflux mechanisms. Dose-dependent antiproliferative effects were observed across three TNBC cell lines, with higher concentrations impairing cellular migration. Mechanistic studies revealed decreased glucose-6-phosphate dehydrogenase expression and elevated reactive oxygen species production, suggesting redox imbalance as a primary mediator of apoptosis. Combination studies with conventional therapeutics showed near-complete eradication of resistant TNBC cells. The observed reduction in p53 levels and increased intranuclear doxorubicin accumulation highlight the AMF/AMF peptide's potential as multidrug resistance modulators. This study underscores the promise of using AMF/AMF peptide as a novel therapeutic approach for TNBC, addressing current treatment limitations and warranting further investigation.

Decitabine Enhances Sorafenib Sensitivity in Renal Cell Carcinoma by Promoting BIN1 and SYNE1 Expressions.

Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), significantly impacts health, and results in particularly poor outcomes in patients at the advanced stage. Resistance to vascular endothelial growth factor (VEGF) pathway-targeting tyrosine kinase inhibitors (TKIs) is a major barrier in effective ccRCC treatment. Herein, we aim to explore how decitabine mediates bridging integrator 1 (BIN1) and spectrin repeat containing nuclear envelope protein 1 (SYNE1) to impact resistance of ccRCC to sorafenib. Employing bioinformatics on datasets GSE64052 and CancerSea, we identified genes linked to TKI resistance, ultimately focusing on SYNE1. We assessed influences of SYNE1 overexpression and BIN1 knockdown via quantitative real-time PCR (qRT-PCR) and Western blot. Assessment of cell viability and apoptosis was accomplished using cell counting kit-8 (CCK-8) assays and flow cytometry. The investigation into the potential interactions between SYNE1 and BIN1, as well as their impacts on sorafenib sensitivity was accomplished by Co-Immunoprecipitation (Co-IP) and Glutathione-S-transferase (GST) Pull-down. SYNE1 was substantially down-regulated in sorafenib-resistant ccRCC cells, and its overexpression increased sorafenib sensitivity, decreased viability and enhanced apoptosis. Interaction between BIN1 and SYNE1 was confirmed, with BIN1 level lower in resistant cells. BIN1 knockdown reduced the beneficial effects of SYNE1 overexpression on sorafenib sensitivity. Decitabine treatment elevated both SYNE1 and BIN1, while boosting apoptosis and reducing sorafenib resistance. SYNE1 contributes to the modulation of sorafenib resistance in ccRCC cells through interacting with BIN1. Decitabine treatment enhances expressions of these two proteins to improve TKI response, suggesting a potential strategy for counteracting resistance and bettering patient outcomes.

Molecular characterization of the tet (M)-carrying transposon Tn7124 and plasmids in Escherichia coli isolates recovered from swine.

Here, we report the genetic features and evolutionary mechanisms of two tet (M)-bearing plasmids (pTA2 and pTA7) recovered from swine Escherichia coli isolates. The genetic profiles of pTA2 and pTA7 and corresponding transconjugants were accessed by S1 nuclease pulsed-field gel electrophoresis and Southern hybridization, followed by whole genome sequencing and bioinformatics analysis. The biological influences of pTA2 and pTA7 were determined by stability and direct competition assays. Both pTA7 and pTA2 had the IncR backbone sequences but differed in the multidrug resistance region (MDR). The MDR of pTA2 consisted of sul3, tet (M), qnrS1, bleO, oqxAB, floR, aadA1, cmlA1, aadA2, and tet (A)-tetR (A) in addition to 22 insertion sequences. Notably, pTA2 carried the novel complex Tn7124 (IS26-ctp-lp-tet (M)-hp-IS406tnp-IntI4-IS26) harboring tet (M). The fragment carrying tet (M) (IS26-ctp-lp-tet (M)-IS406 tnp-ctp-aadA1-cmlA1-aadA2-dfrA12-IntI1), named Tn6942-like, and the two resistance modules ISVsa3-VirD2-floR-lysR and tet (A)-tetR (A) were located in the MDR of pTA7. Both pTA2 and pTA7 were highly stable in E. coli DH5α cells with no fitness cost to the host or disadvantage in growth competition. These results indicate that transposons carrying tet (M) continuously integrate via mediation with an insertion sequence, which accelerates the transmission of tet (M) in E. coli isolates through integration of other drug-resistant genes, thereby posing a potential serious threat to the efficacy of clinical treatment.

Chemical Profile, Antibacterial and Toxicological Study of Asparagus setaceus (KUNTH)

Objective: The objective of this work was to obtain the chemical profile and verify the biological activities of ethanolic extract from the leaves of Asparagus setaceus. Method: The extract was obtained with cold ethanol and the classes of secondary metabolites were identified with specific reagents. The antibacterial assays were performed using the microdilution method against the standard bacteria, Gram +: Sthaphylococcus aureus, Streptococcus mutans and Enterococcus faecalis and Gram -: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoneae and two multidrug-resistant strains: Escherichia coli 27 and Staphylococcus aureus 358 and the resistance modulation assay was performed using aminoglycoside and beta- lactam antibiotics. Toxicity was tested against the microcrustacean Artemia salina (Leach) ranging in concentrations from 10 to 500 μg/mL Results and Discussion: The ethanolic extract of Asparagus setaceus (EEAS) indicated the presence of phenols, condensed tannins, anthocyanins, anthocyanidins, flavones, flavonols, xanthones, chalcones, aurones, flavononols, catechins, leukoanthocyanidins, flavones and saponins. The EEAS presented CL50 of 90.22 μg/ mL. The microbial assay showed inhibition for standard strains of Gram + and Gram bacteria - but in the multidrug-resistant strains it showed clinically non-signific results. For the modulation of antibiotic action against bacterial strains, EEAS presented both synergistic and antagonistic action, with the synergistic action being more expressive on benzylpenicillin, amikacin and gentamicin in front of Escherichia coli 27. The aminoglycoside antibiotics showed synergistic activity on all bacteria tested. Research Implications: Given the results, it was found that the ethanolic extract of the leaves of Asparagus setaceus (Kunth) disp of chemical and biological properties that can contribute to the elaboration of therapeutic resources against inflammatory and bacterial infectious processes. Keywords: Antibacterial Assay, Secondary Metabolites, Modulation, Asparagus setaceus.