Synergistic Efficacy Research Articles

GC-MS/HPLC Profiling and Sono-Maceration Mediated Extraction of Osbeckia Parvifolia Polyphenols: In Silico and In Vitro Analysis on Anti-Proliferative Activity in Ovarian Cancer Cell Lines.

Osbeckia parvifolia, an endemic edible plant of Western Ghats, was investigated in the present study for its polyphenolic compounds, including content, constituents, extraction through an ultrasonic-assisted maceration technique and therapeutic potential in biomedical applications. The methanolic extract (OPM) exhibited an IC50 value of 1.25 μg/mL against 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals. Furthermore, the ethyl acetate and methanolic extracts also strongly inhibited 5-lipoxygenase, especially OPM (84.93 %), which was comparable to standard curcumin. OPM also elicited cytotoxicity in SKOV3 ovarian cancer cells (93.80 %), surpassing paclitaxel. Bio-accessibility analysis demonstrated that the release of phenolic compounds and antioxidant potential were very high (above 100 %), revealing the possibility of synergistic efficacy of polyphenolic complexes in drug development. Gas Chromatography -Mass Spectrometry (GC-MS) analysis revealed 22 bioactive polyphenolic compounds in OPM, such as epicatechin, quercetin, and psoralidin. This was confirmed by High Performance Liquid Chromatography (HPLC) and High-Pressure Thin Layer Chromatography (HPTLC) analyses, which revealed a high quantity of catechin (37.45 mg/g). Molecular docking revealed the significant binding affinity of these proteins for the ovarian oncoproteins PI3K (-8.52 kcal/mol) and Casp-8 (-8.41 kcal/mol). Adsorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profiling indicated the favorable pharmacokinetic properties of these compounds, supporting their candidacy in drug formulations against ovarian cancer.

Potential Therapeutic Targets for Combination Antibody Therapy Against Staphylococcus aureus Infections

Despite the significant advances in antibiotic treatments and therapeutics, Staphylococcus aureus (S. aureus) remains a formidable pathogen, primarily due to its rapid acquisition of antibiotic resistance. Known for its array of virulence factors, including surface proteins that promote adhesion to host tissues, enzymes that break down host barriers, and toxins that contribute to immune evasion and tissue destruction, S. aureus poses a serious health threat. Both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) classify S. aureus as an ESKAPE pathogen, recognizing it as a critical threat to global health. The increasing prevalence of drug-resistant S. aureus underscores the need for new therapeutic strategies. This review discusses a promising approach that combines monoclonal antibodies targeting multiple S. aureus epitopes, offering synergistic efficacy in treating infections. Such strategies aim to reduce the capacity of the pathogen to develop resistance, presenting a potent adjunct or alternative to conventional antibiotic treatments.

Cu-S-Mo Interfacial Sites in CuO2@MoS2/PLLA Scaffolds for Robust Synergistic Antibacterial Efficacy via CDT and PTT

Bacterial infections considerably limit the success of scaffold transplantation. CuO2 may generate hydroxyl radicals through a self-cascade catalytic process, which is effective for sterilization. However, reducing CuO2-derived Cu+ ions to Cu° can lead to a decline in catalytic activity. To overcome these limitations, we anchored CuO2 onto MoS2 to establish stable Cu-S-Mo interfacial sites. The CuO2/MoS2 nanozyme was fabricated using a low-temperature co-precipitation technique and introduced into poly-L-lactic acid scaffolds using selective laser sintering. The Cu-S-Mo interfacial sites showed a triad of functions that synergistically enhanced catalytic performance. These sites stabilized the Cu atoms, augmented catalytic activity by facilitating efficient electron transfer through the Mo4+/Mo6+ redox couple, and improved the conduction of heat derived from the photothermal response of MoS2 to the Cu catalyst. The synergistic action of chemodynamic and photothermal therapy, mediated by the Cu-S-Mo sites, resulted in remarkable antibacterial efficacy, with 92.3% and 93.5% inhibition rates against Staphylococcus aureus and Escherichia coli, respectively. Experimental evidence and simulations demonstrated that Cu-S-Mo structure stabilized the Cu atoms and improved electron transfer via interatomic charge transfer. These results highlight the potential of the CuO2@MoS2/PLLA scaffold in eliminating bacterial infections.

Combined treatment with Aronia berry extract and oligomeric proanthocyanidins exhibit a synergistic anticancer efficacy through LMNB1-AKT signaling pathways in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent and highly recurrent malignancies worldwide and currently ranks as the second leading cause of cancer-related deaths. The high degree of morbidity and mortality associated with CRC is primarily attributed to the limited effectiveness of current therapeutic approaches and the emergence of chemoresistance to standard treatment modalities. Recent research indicates that several natural products, including Aronia berry extracts (ABE) and oligomeric proanthocyanidins (OPCs), might offer a safe, cost-effective, and multitargeted adjunctive role to cancer treatment. Herein, we hypothesized a combined treatment with ABE and OPCs could synergistically modulate multiple oncogenic pathways in CRC, thereby enhancing their anticancer activity. We initially conducted a series of in vitro experiments to assess the synergistic anticancer effects of ABE and OPCs on CRC cell lines. We demonstrate that these two compounds exhibited a superior synergistic anticancer potential versus individual treatments in enhancing the ability to inhibit cell viability, suppress colony formation, and induce apoptosis (p < 0.05). Consistent with our in vitro findings, we validated this combinatorial anticancer effect in tumor-derived 3D organoids (PDOs; p < 0.01). Using genome-wide transcriptomic profiling, we identified that a specific gene, LMNB1, associated with the cell apoptosis pathway, was found to play a crucial role in exhibiting anticancer effects with these two products. Furthermore, the combined treatment of ABE and OPCs significantly impacted the expression of key proteins involved in apoptosis, including suppressed expression levels of LMNB1 in CRC cell lines (p < 0.05), which resulted in inhibiting downstream AKT phosphorylation. In conclusion, our study provides novel evidence of the synergistic anticancer effects of ABE and OPCs in CRC cells, partially mediated through the regulation of apoptosis and the oncogene LMNB1 within the AKT signaling pathway. These findings have the potential to better appreciate the anticancer potential of natural products in CRC and help improve treatment outcomes in this malignancy.

Tailoring Carrier-Free Nanoparticles based on Natural Small Molecule Assembly for Synergistic Anti-tumor Efficacy

Tailoring Carrier-Free Nanoparticles based on Natural Small Molecule Assembly for Synergistic Anti-tumor Efficacy

Synergistic anticancer efficacy of polydatin and sorafenib against the MCF-7 breast cancer cell line via inhibiting of PI3K/AKT/mTOR pathway and reducing resistance to treatment

Polydatin (PD), a glucoside derivative of resveratrol, has been investigated for its potential to mitigate sorafenib (SOF) side effects and combat multidrug resistance in cancer treatment. The study evaluated its mechanism of action for inhibiting the protein kinase B/mTOR pathway in promoting breast cancer proliferation. The combined PD and SOF have synergistic effects with a combination index (CI) < 1 in the liver (HepG2) and breast (MCF-7) cancer cell lines. Molecular docking studies were conducted to analyze interactions of PD& SOF with protein kinases as well as apoptotic and multidrug resistance proteins, including AKT1, PI3K, mTOR, Apaf-1, and ABCB1 in MCF-7 cells. Experimental validation through real-time PCR confirmed. PD has a strong binding affinity, particularly with AKT1 (-56 kcal/mol) and ABCB1 (-27.16 kcal/mol), a gene associated with multidrug resistance. These interactions were linked to anti-proliferative anti-angiogenic effects and reduced resistance to treatment, demonstrating PD has potential therapeutic benefits. Furthermore, PD combined with SOF induced apoptosis, inhibited cell growth, and arrested MCF-7 cells in the sub-G1 phase with increased intracellular ROS. This was accompanied by reduced expression of AKT1 and ABCB1 genes, reinforcing the anticancer efficacy of PD/SOF combination therapy. In conclusion, the findings suggest that PD/SOF could serve as a promising anticancer treatment strategy, warranting further investigation for potential clinical applications and mechanistic studies in vivo.

Assessment of synergistic efficacy of carbaryl in combination with Cinnamomum cassia and Origanum vulgare essential oils against Dermanyssus gallinae

Assessment of synergistic efficacy of carbaryl in combination with Cinnamomum cassia and Origanum vulgare essential oils against Dermanyssus gallinae

A dehydration membrane reactor towards highly efficient LPG synthesis via CO2 hydrogenation

In recent years, CO2 hydrogenation has garnered increasing attention as a promising avenue towards the conversion of captured CO2 to valuable liquid chemicals, including CH3OH, CH3OCH3, and liquified petroleum gas (LPG). However, chemical conversion of CO2 has proven to be immensely challenging, resulting in low CO2 conversion (<35 %) and product yields (<15 %). H2O, unavoidably evolved during CO2 hydrogenation, imposes both thermodynamic and kinetic penalties on CO2 hydrogenation reactions via adsorption on catalyst active sites and promotion of undesirable reaction pathways. In this work, to greatly facilitate direct conversion of CO2 to LPG over a bifunctional Cu/Zn/Zr on Al2O3 (CZZA)/Pd-β-zeolite catalyst, a dehydration membrane reactor (MR) featuring a H2O-conducting Na+-gated nanochannel membrane was studied. Before the incorporation of the Na+-gated membrane, the CZZA/Pd-β-zeolite was unable to produce LPG at 280–310 °C and 14 bar, and the CO2 conversion was limited to < 35 %. In stark contrast, the MR exhibited CO2 conversion and LPG yield of 72.1 % and 51.7 %, respectively. The operating conditions of the MR were systematically investigated to determine the maximum achievable performance resulting in CO2 conversion and LPG yield as high as 90.2 % and 60.5 %, respectively. Furthermore, the LPG space–time yield (STY) at the optimized conditions was near that of the best-performing traditional reactors (TRs) in the literature but at 3 times and 8 times increased CO2 conversion and time factor (W/F), respectively. The MR in this work demonstrates the synergistic efficacy of combined H2O removal and CH3OH consumption towards highly efficient hydrogenation of CO2 for LPG production.

Berberine In Combination With Evodiamine Ameliorates Gastroesophageal Reflux Disease Through TAS2R38/TRPV1-Mediated Regulation of MAPK/NF-κB Signaling Pathways and Macrophage Polarization

BackgroundGastroesophageal reflux disease (GERD) is a chronic condition of the digestive tract with limited therapeutic options. Bitter taste receptors (TAS2Rs) and transient receptor potential vanilloid-1 (TRPV1) are implicated in modulating inflammatory responses. Berberine (BBR) and evodiamine (EVO) are known to activate TAS2Rs and TRPV1, respectively. However, whether BBR and EVO can ameliorate GERD by targeting TAS2Rs and TRPV1 remains uncertain. PurposeThis study aims to determine whether BBR and EVO mitigate esophageal injury by targeting TAS2R38 and TRPV1 and to elucidate their underlying molecular mechanisms. MethodsA GERD rat model was developed using esophagogastric anastomosis, while GERD in human esophageal epithelial cells (HEECs) was induced via bile acid (BA) exposure. Esophageal pathology was analyzed through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). mRNA and protein levels were measured via qRT-PCR, immunofluorescence, immunohistochemistry and Western blot analysis. Small interfering RNA was used to silence TAS2R38 and TRPV1 in HEECs. The activation of TAS2R38 and TRPV1 by BBR and EVO was assessed through Ca2+ mobilization assays. Finally, in vivo validation was conducted using U73122 to inhibit TAS2Rs and resiniferatoxin (RTX) to ablate TRPV1. ResultsBBR and EVO treatments significantly improved esophageal pathology in GERD rats and reduced BA-induced inflammation in HEECs. Additionally, BBR and EVO suppressed proinflammatory factors expression, upregulated barrier proteins such as E-cadherin and claudin-1, and inhibited the phosphorylation of p65, JNK, and ERK in the MAPK/NF-κB signaling pathways in both in vivo and in vitro models. Furthermore, BBR and EVO, whether individually or in combination, reduced dilated intercellular spaces (DIS), increased desmosome numbers, and modulated macrophage polarization in GERD rats. Knockdown of TAS2R38 and TRPV1 in HEECs notably diminished the stimulatory effects of BBR and EVO. Moreover, the regulation of barrier function and MAPK/NF-κB pathway proteins by BBR and EVO in BA-induced HEECs was abrogated upon TAS2R38 and TRPV1 knockdown. Similarly, U73122 and RTX reversed the effects of BBR and EVO on macrophage polarization and MAPK/NF-κB signaling pathways in vivo. ConclusionWe firstly demonstrate that BBR and EVO alleviate GERD, with enhanced synergistic efficacy observed when used in combination. Mechanistically, BBR and EVO activate the TAS2R38 and TRPV1, respectively, leading to downregulation of phosphorylation in MAPK/NF-κB signaling pathways and modulation of macrophage polarization. These findings offer a novel foundation for the clinical application of BBR and EVO in GERD treatment.

Nuclear imaging of PD-L1 expression promotes the synergistic antitumor efficacy of targeted radionuclide therapy and immune checkpoint blockade.

In order to maximize synergistic effect of targeted radionuclide therapy (TRT) and immune checkpoint blockade (ICB) as well as reduce the toxicity, we pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards precision cancer therapy. As a novel targeted radiotherapeutic agent, 177Lu-AB-3PRGD2 targeting integrin αvβ3 was developed to achieve sustained antitumor effect by introducing an albumin binder (AB) into the structure of 3PRGD2. The 177Lu-AB-3PRGD2 TRT as well as different types of combination therapies of 177Lu-AB-3PRGD2 TRT and anti-PD-L1 ICB were performed in animal models. The changes of PD-L1 expression in tumors after TRT were evaluated in vitro and in vivo by PD-L1-specific SPECT/CT imaging of 99mTc-MY1523. 177Lu-AB-3PRGD2 showed improved tumor uptake and prolonged tumor retention, leading to significantly enhanced tumor growth suppression. Moreover, 177Lu-AB-3PRGD2 TRT remodeled the tumor immune microenvironment by upregulating PD-L1 expression and increasing tumor-infiltrating CD8+ T cells, facilitating immunotherapy. We found that the anti-PD-L1 treatment was more effective during the upregulation of tumor PD-L1 expression, and the time window could be determined by 99mTc-MY1523 SPECT/CT. We developed a novel and long-acting radiotherapeutic agent 177Lu-AB-3PRGD2, and pioneered a strategy guided by PD-L1-targeted nuclear medicine imaging for the combination of TRT and ICB towards precision cancer therapy, optimizing the therapeutic efficacy and reducing the cost and potential toxicity risks. This strategy could also be adapted for clinical practice, combining conventional radiotherapy or chemotherapy with ICB to enhance therapeutic efficacy.

Advance Screening of Bis- Azetidinone Derivatives: Synthesis, Spectroscopy, Antioxidant and Antimicrobial Analysis with Molecular Docking Assessment

Introduction: This study includes synthesis, characterizations, antimicrobial, antiox-idant, and docking molecular study of novel Bis-Azetidinone compounds that combined two units of β-lactam rings .In the present investigation, the aromatic aldehydes with primary amine were condensed to create Schiff's base, which was then reacted with chloroacetylchloride to pro-duce bis-Azetidinone compounds. Methods: Melting points, FTIR, and NMR spectrum analyses were used to examine the mor-phological and topological characteristics of the Bis-Azetidinone compounds. The results indi-cate that the prepared Compounds synthesis has excellent antimicrobial activity against both Gram-negative (Escherichia coli,), Gram-positive bacteria (Staphylococcus aureus) and fungal (Candida albicans) and also indicated that the Compounds synthesis (A2) gave a higher antimi-crobial effect than the B2, C2. The synergistic activity was examined against the pathogenic microbial strains. It was observed that employing compound synthesis combined with antibiot-ics enhanced the synergistic efficacy compared to using compound synthesis alone or antibiotic alone on Gram-positive bacteria and fungi. Results: The antioxidant efficiency was assessed by DPPH, the results show that the compound synthesis has antioxidant activity, and also indicated that the synthesized compound (A2) gave a higher antioxidant effect than the B2, C2. Docking study confirmed via redocking of crystal-ized substrate or inhibitor within target binding pocket. The docking results reveal that the syn-thesized compounds, with a total binding affinity of less than -48 kcal/mol, could be clinically used for future therapeutic purposes. Conclusion: The present research demonstrates the advantageous effectiveness of a simpler pro-duction procedure, novel Bis-Azetidinone compounds, for producing high-purity with low haz-ard that may be utilized as future possible medical therapies.

Integrated microbiome and metabolome analysis reveals synergistic efficacy of basil polysaccharide and gefitinib in lung cancer through modulation of gut microbiota and fecal metabolites

Emerging evidence suggests that gut microbiota and its metabolites significantly influence the effectiveness of EGFR-TKIs (e.g., gefitinib, erlotinib) in lung cancer treatment. Plant polysaccharides can interact with gut microbiota, leading to changes in the host-microbe metabolome that may affect drug metabolism and therapeutic outcomes. Our previous research demonstrated the efficacy of basil polysaccharide (BPS) in treating various cancers by regulating hypoxic microenvironment and inhibiting epithelial-mesenchymal transition process. However, the potential impact of BPS on gut microbiota has not been thoroughly explored. In this study, we employed an immunodeficient gefitinib-resistant xenograft mouse model to explore whether BPS enhances the antitumor effects of gefitinib. A multi-omics approach, including 16S rDNA amplicon sequencing and LC-MS, was used to elucidate these synergistic effects. Our findings indicate that BPS can enhance tumor responsiveness to gefitinib by modulating the gut microbiota and its metabolites through multiple metabolic pathways. These changes in gut microbiota and metabolites could potentially affect cancer related signaling pathway and lung resistance-related protein, which are pivotal in determining the efficacy of EGFR-TKIs in cancer treatment.

Drug-Drug Cocrystal Alloy and Nanoformulation of Cytarabine: Optimized Biopharmaceutical Property and Synergistic Antitumor Efficacy.

An integrated strategy by combining cocrystallization with nanotechnology is developed to optimize in vitro/vivo performances of marine antitumor drug cytarabine (ARA) and further obtain innovative insights into the exploitation of cocrystal alloy nanoformulation. Therein, the optimization of properties and synergistic effects of ARA mainly depends on assembling with uracil (U) and antitumor drug 5-fluorouracil (FU) into the same crystal by cocrystallization technology, while the long-term efficacy is primarily maintained by playing the superiority of nanotechnology. Along this line, the first cocrystal alloy of ARA, viz., ARA-FU-U (0.6:0.4), is successfully obtained and then transformed into a nanocrystal. Single-crystal X-ray diffraction analysis demonstrates that this cocrystal alloy consists of two isomorphic cocrystals of ARA, namely, ARA-FU and ARA-U, in 0.6:0.4 ratio. An R22(8) hydrogen-bonding cyclic system formed by a cytosine fragment of ARA with U or FU can protect and stabilize the amine group on ARA, laying the foundation for regulating its properties. The in vitro/in vivo properties of the cocrystal alloy and its nanocrystals are investigated by theoretical and experimental means. It reveals that both the alloy and nanocrystal can improve physicochemical properties and promote drug absorption, thus bringing to optimized pharmacokinetic behaviors. The nanocrystal produces superior effects than the alloy that helps to extend therapeutic time and action. Particularly, relative to the corresponding binary cocrystal, the synergistic antitumor activity of ARA and FU in the cocrystal alloy is heightened obviously. It may be that U contributes to reducing the degradation of FU, specifically increasing its concentration in tumors to enhance the synergistic effects of FU and ARA. These findings provide new thoughts for the application of cocrystal alloys in the marine drug field and break fresh ground for cocrystal alloy formulations to optimize drug properties.

Intrinsic Synergy and Selectivity for the Inhibition of Cancer Cell Growth Generated by a Polymer Ligand of Proximal Enzymes.

A fundamental understanding of the design of polymer ligands of proximal enzymes is essential for the precise targeting of cancer cells, but it is still in its infancy. In this study, we systematically investigated the contribution of the chain length, ligand density, and ligand ratio of proximal enzyme-targeted polymers to the efficacy, synergy, and selectivity for the inhibition of cancer cell proliferation. The results revealed that employing a moderate chain length as a scaffold allowed for an intrinsically high efficacy and synergy of proximal enzyme-targeted polymers, in contrast to single enzyme-targeted polymers that prefer longer chain length for efficacy. The synergy obtained in proximal enzyme targeting was not provided by the combination of the corresponding small molecules. Moreover, the maturation of the synergistic efficacy of the proximal enzyme-targeted polymers also improved selectivity. This study proposes a rational design for polymer inhibitors and/or ligands for cancer cells with a high efficacy and selectivity.

Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.

Synergistic and Broad-Spectrum Efficacy of Phenylacetate and Acetophenone Combination Against Mycotoxin-Producing Fungi

Synergistic and Broad-Spectrum Efficacy of Phenylacetate and Acetophenone Combination Against Mycotoxin-Producing Fungi

The novel and potent CD40 agonist KHK2840 augments the antitumor efficacy of anti-PD-1 antibody and paclitaxel.

Lack of tumor-reactive cytotoxic T lymphocytes (CTLs)limits the antitumor efficacy of immune checkpoint inhibitors (ICIs). CD40 agonists have been expected to overcome this limitation by generating tumor-reactive CTLs. However, the clinical efficacy of CD40 agonistic antibodies is not as good as in non-clinical studies. The novel human CD40 (hCD40) agonist KHK2840 is a fully human anti-CD40 IgG2 agonistic antibody that is Fc-engineered to minimize complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Compared to other hCD40 agonists, KHK2840 exhibited the most potent hCD40 agonistic signal in tumor-bearing hCD40 transgenic mice and human peripheral blood B cells. Moreover, KHK2840 enhanced the antitumor efficacy of the antiprogrammed cell death 1 antibody and paclitaxel. Comprehensive immune profiling revealed that the antitumor immune response of the triple combination involved tumor-draining lymph nodes in addition to tumor microenvironments. This suggests that a coordinated antitumor immune response between tumors and lymph nodes may underlie the synergistic antitumor efficacy of the triple combination therapy. Finally, a toxicology study in cynomolgus monkeys demonstrated that KHK2840 activated the CD40 signal with tolerable toxicological properties. These results indicate that KHK2840 is a novel and potent hCD40 agonistic antibody for cancer immunotherapy, which is expected to augment the antitumor efficacy of ICIs and chemotherapy.

Synergistic corrosion inhibition of 4-hydroxypyridine and halogen ions: Insights from interfacial nonlinear spectroscopy.

4-Hydroxypiridine (4-HPy) is a green chemistry corrosion inhibitor for low-carbon steel, valued for its environmental compatibility and low toxicity. Despite lower initial effectiveness than 4-mercapto/4-aminopyridine, 4-HPy's performance is markedly enhanced by halogen ions. By employing second harmonic generation (SHG) spectroscopy combined with electrochemical methods, Raman spectroscopy, atomic force microscopy, x-ray photoelectron spectroscopy, and in situ UV spectroscopy, this study elucidates the synergistic enhancement mechanism of 4-HPy with Cl-, Br-, and I- in 0.5 mol/L HCl solution. Time-dependent SHG measurements showed a two-step process of rapid adsorption and subsequent orientation change, with a proposed mechanism to interpret the temporal changes in SHG intensity. Deducing the adsorption kinetic equations and their application to the experimental data yields the adsorption rate (kad) and orientation change rate (Kre). Halogens reduce the orientation angle of 4-HPy, facilitating its adsorption on the substrate surface and effectively inhibiting corrosion via distinct mechanisms. Cl- and Br- ions primarily adsorb onto the metal surface, forming an adsorption film that not only enhances the subsequent adsorption of 4-HPy but also provides a protective effect for the metal surface. Conversely, I- forms mainly complexes with 4-HPy in solution, co-adsorbs onto the metal surface, and demonstrates a significant synergistic effect. This study revealed the synergistic efficacy hierarchy among halogen ions, with the order 4HPy + NaCl < 4HPy + NaBr < 4HPy + NaI. This study enhances our molecular-level understanding of the synergistic mechanism between halogen ions and corrosion inhibitors and provides valuable insights for designing and developing effective corrosion inhibitors.

Enhanced Synergistic Efficacy Against Breast Cancer Cells Promoted by Co-Encapsulation of Piplartine and Paclitaxel in Acetalated Dextran Nanoparticles.

Malignant breast tumors constitute the most frequent cancer diagnosis among women. Notwithstanding the progress in treatments, this condition persists as a major public health issue. Paclitaxel (PTX) is a first-line classical chemotherapeutic drug used as a single active pharmaceutical ingredient (API) or in combination therapy for breast cancer (BC) treatment. Adverse effects, poor water solubility, and inevitable susceptibility to drug resistance seriously limit its therapeutic efficacy in the clinic. Piplartine (PPT), an alkaloid extracted from Piper longum L., has been shown to inhibit cancer cell proliferation in several cell lines due to its pro-oxidant activity. However, PPT has low water solubility and bioavailability in vivo, and new strategies should be developed to optimize its use as a chemotherapeutic agent. In this context, the present study aimed to synthesize a series of acetalated dextran nanoparticles (Ac-Dex NPs) encapsulating PPT and PTX to overcome the limitations of PPT and PTX, maximizing their therapeutic efficacy and achieving prolonged and targeted codelivery of these anticancer compounds into BC cells. Biodegradable, pH-responsive, and biocompatible Ac-Dex NPs with diameters of 100-200 nm and spherical morphologies were formulated using a single emulsion method. Selected Ac-Dex NPs containing only PPT or PTX as well as those coloaded with PPT and PTX achieved excellent drug-loading capabilities (PPT, ca. 11-33%; PTX, ca. 2-14%) and high encapsulation efficiencies (PPT, ∼57-98%; PTX, ∼80-97%). Under physiological conditions (pH 7.4), these NPs exhibited excellent colloidal stability and were capable of protecting drug release, while under acidic conditions (pH 5.5) they showed structural collapse, releasing the therapeutics in an extended manner. Cytotoxicity results demonstrated that the encapsulation in Ac-Dex NPs had a positive effect on the activities of both PPT and PTX against the MCF-7 human breast cancer cell line after 48 h of treatment, as well as toward MDA-MB-231 triple-negative BC cells. PPT/PTX@Ac-Dex NPs were significantly more cytotoxic (IC50/PPT = 0.25-1.77 μM and IC50/PTX = 0.07-0.75 μM) and selective (SI = 2.9-6.7) against MCF-7 cells than all the control therapeutic agents: free PPT (IC50 = 4.57 μM; SI = 1.2), free PTX (IC50 = 0.97 μM; SI = 1.0), the single-drug-loaded Ac-Dex NPs, and the physical mixture of both free drugs. All combinations of PPT and PTX resulted in pronounced synergistic antiproliferative effects in MCF-7 cells, with an optimal molar ratio of PPT to PTX of 2.3:1. PPT/PTX-2@Ac-Dex NPs notably promoted apoptosis, cell cycle arrest at the G2/M, accumulation of intracellular reactive oxygen species (ROS), and combined effects from both PPT and PTX on the microtubule network of MCF-7 cells. Overall, the combination of PTX and PPT in pH-responsive Ac-Dex NPs may offer great potential to improve the therapeutic efficacy, overcome the limitations, and provide effective simultaneous delivery of these therapeutics for BC treatment.

Synergistic efficacy of ZnO quantum dots, Ag NPs, and nitazoxanide composite against multidrug-resistant human pathogens as new trend of revolutionizing antimicrobial treatment

Antibiotic resistance is currently becoming a more serious threat to global health, especially in severe nosocomial infections treatment by multidrug-resistant bacteria. This research provides a new way of synergizing green-synthesis for zinc oxide quantum dots (ZnO-QDs with hexagonal crystals) that are 7 nm in diameter and zero-valent Ag cubic crystals that are 67 nm in size embedded with nitazoxanide substrate (NAZ). Instrumental characterization like SEM, TEM, EDAX, and FT-IR and comprehensive antimicrobial studies were conducted to study the incorporation behavior of composites based on Ag NPs/ZnO QDs/NAZ. This combination has not been hitherto addressed anywhere else in the published literature, as well as commercial viability. In this context, we have precisely tuned nanoparticle to nitazoxanide ratio for designing the formulation demonstrating potent activity against MDR infections. By employing nitazoxanide as a scaffold and careful decoration thereof antimicrobial potency has been unlocked overriding conventional therapies. In addition, Ag NPs/ZnO-QDs/nitazoxanide (G6) formula exhibited a therapeutic efficacy span of 96.15 ± 1.68% to 99.57 ± 0.20% against MDR human infections post 48 h incubation; a breakthrough in therapeutic efficacy levels has been achieved by our method. Accordingly, ZnO QDs/Ag NPs/NAZ composite offered potential multidrug resistant human pathogens as a new trend of revolutionizing antimicrobial treatment.Graphical abstractSchematic diagram of synthesis routev ZnO quantum dots/Ag NPs/Nitazoxanide Triumphs composite NPs.