Synergistic Potential Research Articles

Exploration and application of treating OSCC by a precisely concentrated synergistic agent in combination with thermally responsive release of effective therapeutic dosages of cisplatin

Platinum-based drugs, foremost among them Cisplatin (CDDP), currently constitute the primary line of chemotherapy for the treatment of oral squamous cell carcinoma (OSCC). However, the extensive utilization of these drugs often results in undesirable systemic toxic side effects. Consequently, in clinical practice, emphasis has shifted towards the adoption of combination drug strategies, aimed at minimizing the dosage of platinum-based drugs while preserving optimal anti-tumor efficacy. Prior research has concentrated on the co-loading of drugs with synergistic potential into a unified nanosystem, yet this approach does not guarantee that the drugs will remain within the concentration range necessary for synergistic effects following nanocarrier release, thus limiting the full exploitation of their synergistic anti-tumor properties. This study has pioneered the discovery that the HSP90 inhibitor 17AAG exhibits remarkable synergistic effects with CDDP in the treatment of OSCC. Importantly, 17AAG can allow CDDP to still exert effective tumor killing effects at lower concentrations. Furthermore, specific concentrations of 17AAG demonstrate synergistic effects with a wide range of CDDP concentrations, positioning it as a promising candidate for the sustained synergistic augmentation of CDDP released from nanocarriers. Additionally, we have augmented CDDP targeting through the employment of a hybrid membrane strategy, encapsulating CDDP and photosensitizers concurrently. This approach enhances CDDP’s targeting precision and enables responsive tracking and release. Notably, we have observed that altering the tumor cell membrane type significantly modifies the tumor targeting profile of the hybrid membrane, suggesting that cell membrane-modified nanocarriers have potential value in achieving personalized tumor therapy. In summary, we have formulated a novel CDDP-based targeted therapy strategy for OSCC, which holds promising implications for future treatment of this malignancy.

New horizon of the combined BCG vaccine with probiotic and liraglutide in augmenting beta cell survival via suppression of TXNIP/NLRP3 pyroptosis signaling in Streptozocin–Induced diabetes mellitestype-1 in rats

BackgroundAn ideal anti-diabetic type-1 pharmacotherapy should combine abrogation of beta cell pyroptosis with enhancement of beta cell mass. ObjectivesThe study investigated the potential synergism from combining the Bacillus Calmette-Guerin (BCG) vaccine with liraglutide (LIR) and probiotics in mitigating Streptozocin (STZ)-induced Type1diabetes mellitus in albino rats via suppression of TXNIP/NLRP3 signaling. Methods: Induction of diabetes was performed by two I.V. injections of 50 mg/kg of STZ in male Wistar rats. Forty-eight rats were randomly allocated into six groups: Normal control group; STZ -diabetic group; BCG group; BCG + LIR group; BCG + probiotic group; BCG + LIR + probiotic group. The rats were sacrificed after 8 weeks of treatment. ResultsThe STZ-diabetic group exhibited significant elevation of fasting blood sugar and HbA1c with remarkably decreased serum insulin along with a considerable increase in pancreatic proinflammatory cytokines (TNF-α, NLRP3, IL-1β, and NFκB) and apoptotic markers (ASK-1, IAPP, TXNIP, and Caspase-3) with prominently compromised oxidative scavenging capacity in addition to structural alteration in the pancreatic histoarchitecture with decreased insulin immunostaining. Conversely, diabetic-treated groups, especially the BCG + LIR + probiotic group, were superior in amelioration of STZ-induced pyroptosis of pancreatic islets evidenced by a significant decline in inflammatory cytokines and apoptotic markers with a remarkable upgrade in redox balance, Furthermore, the mitigation in the altered histopathological picture of the pancreas with enhanced insulin immunostaining has been was mirrored on the significant improvement of glucose homeostasis parameters. ConclusionsNoteworthy, BCG combination with liraglutide and probiotic might be a promising repurposed therapeutic modality in the management of type-1 diabetes mellites via targeting pancreatic TXNIP/NLRP3 signaling pathway.

Enhancing Cisplatin Efficacy in Hepatocellular Carcinoma with Selenocystine: The Suppression of DNA Repair and Inhibition of Proliferation in Hepatoma Cells

Cisplatin (cDDP) is a crucial chemotherapy drug for treating various cancers, including hepatocellular carcinoma (HCC). However, its effectiveness is often hindered by side effects and drug resistance. Selenocystine (SeC) demonstrates potential as an anticancer agent, particularly by inhibiting DNA repair mechanisms. This study explored the synergistic potential of SeC combined with cDDP for treating HCC. Our results show that SeC pretreatment followed by cDDP significantly suppresses HCC cell proliferation more effectively than either treatment alone, with minimal toxicity to normal liver cells. The combination induces significant DNA damage by inhibiting homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Xenograft experiments confirmed that the combined therapy strongly inhibits tumor growth. SeC boost the effectiveness of cDDP by amplifying DNA damage and inhibiting DNA repair, presenting a promising approach to enhancing liver cancer treatment.

Synergistic Potential of Nanomedicine in Prostate Cancer Immunotherapy: Breakthroughs and Prospects.

Given the global prevalence of prostate cancer in men, it is crucial to explore more effective treatment strategies. Recently, immunotherapy has emerged as a promising cancer treatment due to its unique mechanism of action and potential long-term effectiveness. However, its limited efficacy in prostate cancer has prompted renewed interest in developing strategies to improve immunotherapy outcomes. Nanomedicine offers a novel perspective on cancer treatment with its unique size effects and surface properties. By employing targeted delivery, controlled release, and enhanced immunogenicity, nanoparticles can be synergized with nanomedicine platforms to amplify the effectiveness of immunotherapy in treating prostate cancer. Simultaneously, nanotechnology can address the limitations of immunotherapy and the challenges of immune escape and tumor microenvironment regulation. Additionally, the synergistic effects of combining nanomedicine with other therapies offer promising clinical outcomes. Innovative applications of nanomedicine include smart nanocarriers, stimulus-responsive systems, and precision medicine approaches to overcome translational obstacles in prostate cancer immunotherapy. This review highlights the transformative potential of nanomedicine in enhancing prostate cancer immunotherapy and emphasizes the need for interdisciplinary collaboration to drive research and clinical applications forward.

Soil-water retention capacity of expansive soil improved through enzyme induced carbonate precipitation-eggshell powder

Enzyme Induced Carbonate Precipitation (EICP) has been extensively investigated as a promising approach to improve engineering properties of soil, while Eggshell Powder (ESP) is an agricultural waste that effectively fills soil pores. The ESP provides abundant nucleation at sites for the EICP process, further promoting the effective precipitation of calcium carbonate. The research presented in this paper investigated the Soil Water Characteristic Curves (SWCC), permeability coefficient, and microstructure of expansive soil before and after EICP and EICP+ESP modification. A series of laboratory experiments were conducted, including soil water characteristic tests, permeability tests and Scanning Electron Microscopy (SEM). The results proved that the addition of EICP and EICP+ESP into natural expansive soil resulted in a gradual decline in air entry value, residual water content, and permeability coefficient, indicating an increase in water retention capacity and a decrease in permeability. Furthermore, with the intrusion of EICP and EICP+ESP, the contact between particles becomes smoother, and the soil pores become more equally distributed. Ultimately, there was an enhancement in water retention capacity of the natural expansive soil. This study emphasizes the synergistic potential of combining EICP and EICP+ESP as stabilizing additives to enhance the water retention capacity of expansive soil. Moreover, the reuse of ESP provides a sustainable solution for the resource utilization of agricultural waste and the improvement of expansive soil using bio-inspired methods.

The synergistic potential of polyethylene glycol 400 for the control of Hyphantria cunea larvae by Beauveria bassiana

The efficacy of entomopathogenic fungi as pest control agents is constrained by both their physiological state and external environmental factors. This study identified synergists capable of enhancing the insecticidal activity of Beauveria bassiana (Bb) and investigated the underlying synergistic mechanisms. Our results found that among 6 potential synergists, polyethylene glycol 400 (PEG) and trehalose significantly improved Bb's lethality against Hyphantria cunea larvae, with PEG demonstrating the most pronounced effect. PEG treatment markedly increased Bb spore adhesion and germination rates, while spore hydrophobicity and growth rates remained unaffected. Moreover, PEG-treated spores exhibited higher thermal tolerance compared to untreated ones. In the Bb + PEG treatment group, the hemocyte count, encapsulation and melanization activities, and the expression of related regulatory genes were significantly lower than those in the Bb treatment group. Additionally, pathogen recognition, signal transduction, and humoral immunity effector genes expression were markedly suppressed in the Bb + PEG group. A significant reduction in the content of total amino acids, free fatty acids, glucose, and trehalose, alongside decreased expression of key regulatory genes in the tricarboxylic acid cycle and glycolysis pathways, was observed in the Bb + PEG treatment group. Furthermore, PEG enhanced Bb-induced apoptosis in H. cunea larvae, as evidenced by the upregulation of apoptosis-related genes. Notably, PEG alone did not significantly impact the innate immunity, energy metabolism, or apoptosis in H. cunea larvae. Overall, PEG exhibits considerable potential in amplifying Bb's insecticidal activity by directly optimizing spore performance and indirectly modulating the larvae's innate immunity, energy metabolism, and apoptosis.

Etodolac utility in osteoarthritis: drug delivery challenges, topical nanotherapeutic strategies and potential synergies.

Osteoarthritis (OSA) is a prevalent joint disorder characterized by losing articular cartilage, primarily affecting the hip, knee and spine joints. The impact of OSA offers a major challenge to health systems globally. Therapeutic approaches encompass surgical interventions, non-pharmacological therapies (exercise, rehabilitation, behavioral interventions) and pharmacological treatments. Inflammatory processes within OSA joints are regulated by pro-inflammatory and anti-inflammatory cytokines. Etodolac, a COX-2-selective inhibitor, is the gold standard for OSA management and uniquely does not inhibit gastric prostaglandins. This comprehensive review offers insights into OSA's pathophysiology, genetic factors and biological determinants influencing disease progression. Emphasis is placed on the pivotal role of etodolac in OSA management, supported by both preclinical and clinical evidences in topical drug delivery. Notably, in-silico docking studies suggested potential synergies between etodolac and baicalein, considering ADAMTS-4, COX-2, MMP-3 and MMP-13 as essential therapeutic targets. Integration of artificial neural network (ANN) techniques with nanotechnology approaches emerges as a promising strategy for optimizing and personalizing topical etodolac delivery. Furthermore, the synergistic potential of etodolac and baicalein warrants in-depth exploration. Hence, by embracing cutting-edge technologies like ANN and nanomedicine, the optimization of topical etodolac delivery could guide a new era of OSA treatment.

Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy.

Carboplatin (Cp) is a potent chemotherapeutic agent, but its effectiveness is constrained by its associated side effects. Frankincense, an oleo-gum resin from the Boswellia sacra tree, has demonstrated cytotoxic activity against cancer cells. This study explored the synergistic potential of nanoparticles formulated from Boswellia sacra methanolic extract (BME), to enhance the therapeutic efficacy of Cp at reduced doses. Nanoparticles were prepared via the nanoprecipitation method, loaded with Cp, and coated with positively charged chitosan (CS) for enhanced cell interaction, yielding Cp@CS/BME NPs with an average size of 160.2 ± 4.6 nm and a zeta potential of 12.7 ± 1.5 mV. In vitro release studies revealed a pH-sensitive release profile, with higher release rates at pH 5.4 than at pH 7.4, highlighting the potential for targeted drug delivery in acidic tumor environments. In vitro studies on HT-29 and Caco-2 colorectal cancer cell lines demonstrated the nanoformulation's ability to significantly increase Cp uptake and cytotoxic activity. Apoptosis assays further confirmed increased induction of cell death with Cp@CS/BME NPs. Cell-cycle analysis revealed that treatment with Cp@CS/BME NPs led to a significant increase in the sub-G1 phase, indicative of enhanced apoptosis, and a marked decrease in the G1-phase population coupled with an increased G2/M-phase arrest in both cell lines. Further gene expression analysis demonstrated a substantial downregulation of the anti-apoptotic gene Bcl-2 and an upregulation of the pro-apoptotic genes Bax, PUMA, and BID following treatment with Cp@CS/BME NPs. Thus, this study presents a promising and innovative strategy for enhancing the therapeutic efficacy of chemotherapeutic agents using naturally derived ingredients while limiting the side effects.

Synthesis and in vitro Biological Evaluation of a Series of 5-Benzylidene Derivatives of Rhodanine-Sulfonylurea Hybrid as a Novel Class of α-Glucosidase Inhibitors

A novel rhodanine-sulfonylurea hybrid (C) has been prepared based on the isocyanate-amine reaction conditions in the first step and its 5-benzylidene analogues (C1-C13) were synthesized using Knoevenagel reaction conditions as the subsequent step. The physical and spectral characterization of all the synthesized compounds (C-C13) was performed using FT-IR, 1H NMR and HR-ESI-MS spectral methods. All compounds were subjected to in vitro α-glucosidase enzyme inhibitory properties at 100 µM concentration. The results were compared with a standard drug, voglibose, also tested at the similar concentrations. The bioassay results revealed that the intermediate compound C was more potent with a percentage inhibitory activity of 64.86%, which is relatively better than the series of 5-benzylidene analogues (C1-C13) synthesized from the intermediate C. This clearly displayed that substitution at position-5 on the rhodanine ring of intermediate C is not a favourable substitution to enhance the bioactivity; however, one of the derivative compounds, C12, has exhibited potency of 58.32%, which is close to the compound C. It is significant that both the intermediate C and compound C12 displayed better potency compared to the standard voglibose, with percentage inhibition recorded at 37.75%. The additive or synergistic potential of the bioactive pharmacophore tosylurea, which was earlier established, tolerated the rhodanine ring substitution towards retaining the α-glucosidase inhibitory properties.

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 μg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

Synergistic Effect of Metronidazole and Chlorhexidine against Porphyromonas gingivalis Growth: An In Vitro Study.

Aim: To evaluate the potential synergistic activity of metronidazole (MTZ) and chlorhexidine (CHX) against Porphyromonas. gingivalis (P. gingivalis) growth. Methods: Antimicrobial susceptibility tests of P. gingivalis to MTZ and CHX were performed on in vitro serial 2-fold dilutions of MTZ (from 1 mg/mL to 0.015 mg/mL) and CHX (from 1 mg/mL to 0.03 mg/mL) in thioglycollate medium broth in a 96-well plate. The turbidity of each sample was analyzed by absorbance spectrophotometry at 450 nm wavelengths by using an enzyme-linked immunosorbent assay (ELISA) reader. The MIC50 (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) were assessed. To investigate the potential synergism between MTZ and CHX, bacterial cells were treated with MTZ or CHX, as described above, either alone or in combination. Results: The MIC50 of MTZ was 0.03 mg/mL while that of CHX ranged from 0.12 to 0.06 mg/mL. MTZ and CHX exerted a significant inhibitory effect on P. gingivalis growth in a dose-dependent manner. MTZ at a low and ineffective concentration of 0.015 mg/mL, associated with a suboptimal concentration of CHX (0.03 mg/mL), exhibited a significant synergistic inhibitory effect on bacterial growth (50% inhibition vs. control) (p < 0.001), and the effect was more remarkable with 0.06 mg/mL CHX (75% inhibition vs. control). Conclusions: CHX and MTZ showed a significant synergistic effect against P. gingivalis growth. A non-effective concentration of MTZ (0.015 mg/mL) combined with suboptimal concentrations of CHX (0.03 mg/mL and 0.06 mg/mL) were related to a 50% growth in the inhibition and 99.99% death of P. gingivalis, respectively. The applicability of the clinical use of these concentrations should be tested in randomized controlled trials.

Methanolic Extract of Cimicifuga foetida Induces G1 Cell Cycle Arrest and Apoptosis and Inhibits Metastasis of Glioma Cells.

Glioblastoma multiforme (GBM) is among the most aggressive and challenging brain tumors, with limited treatment options. Cimicifuga foetida, a traditional Chinese medicine, has shown promise due to its bioactive components. This study investigates the anti-glioma effects of a methanolic extract of C. foetida (CF-ME) in GBM cell lines. The effects of CF-ME and its index compounds (caffeic acid, cimifugin, ferulic acid, and isoferulic acid) on GBM cell viability were assessed using MTT assays on U87 MG, A172, and T98G cell lines. The ability of CF-ME to induce cell cycle arrest, apoptosis, and autophagy and inhibit metastasis was evaluated using flow cytometry, Western blotting, and functional assays. Additionally, the synergistic potential of CF-ME with temozolomide (TMZ) was explored. CF-ME significantly reduced GBM cell viability in a dose- and time-dependent manner, induced G1 phase cell cycle arrest, promoted apoptosis via caspase activation, and triggered autophagy. CF-ME also inhibited GBM cell invasion, migration, and adhesion, likely by modulating epithelial-mesenchymal transition (EMT) markers. Combined with TMZ, CF-ME further enhanced reduced GBM cell viability, suggesting a potential synergistic effect. However, the individual index compounds of CF-ME exhibited only modest inhibitory effects, indicating that the full anti-glioma activity may result from the synergistic interactions among its components. CF-ME exhibited potent anti-glioma activity through multiple mechanisms, including cell cycle arrest, apoptosis, autophagy, and the inhibition of metastasis. Combining CF-ME with TMZ further enhanced its therapeutic potential, making it a promising candidate for adjuvant therapy in glioblastoma treatment.

Development of Novel ROCK Inhibitors via 3D-QSAR and Molecular Docking Studies: A Framework for Multi-Target Drug Design.

Background/Objectives: Alterations in the actin cytoskeleton correlates to tumor progression and affect critical cellular processes such as adhesion, migration and invasion. Rho-associated coiled-coil-containing protein kinases (ROCK1 and ROCK2), important regulators of the actin cytoskeleton, are frequently overexpressed in various malignancies. The aim of this study was therefore to identify the key structural features of ROCK1/ROCK2 inhibitors using computer-aided drug design (CADD) approaches. In addition, new developed ROCK inhibitors provided a significant framework for the development of multitarget therapeutics-ROCK/HDAC (histone deacetylases) multitarget inhibitors. Methods: 3D-QSAR (Quantitative structure-activity relationship study) and molecular docking study were employed in order to identify key structural features that positively correlate with ROCK inhibition. MDA-MB-231, HCC1937, Panc-1 and Mia PaCa-2 cells were used for evaluation of anticancer properties of synthesized compounds. Results: C-19 showed potent anti-cancer properties, especially enhancement of apoptosis and cell cycle modulation in pancreatic cancer cell lines. In addition, C-19 and C-22 showed potent anti-migratory and anti-invasive effects comparable to the well-known ROCK inhibitor fasudil. Conclusions: In light of the results of this study, we propose a novel multi-target approach focusing on developing dual HDAC/ROCK inhibitors based on the structure of both C-19 and C-22, exploiting the synergistic potential of these two signaling pathways to improve therapeutic efficacy in metastatic tumors. Our results emphasize the potential of multi-target ROCK inhibitors as a basis for future cancer therapies.

Heterogeneous Electrocatalysts for Electrochemical Cross‐Coupling Reactions

AbstractElectro‐organic synthesis, a method that uses electrical current to drive various organic transformations, has garnered significant attention, and so has heterogeneous electrosynthesis, a process that produces chemicals through electrochemical reactions at the interface between the electrode and an electrolyte. This concept highlights the synergistic potential of heterogeneous electrocatalysts, particularly in their use in cross‐coupling reactions. After thoroughly analyzing existing literature, key examples have been highlighted in this paper where heterogeneous electrocatalysts have facilitated the transformation of simple starting materials into useful products. This process lowers energy consumption and reduces waste. We hope this short review sparks the interest among those involved in organic electrosynthesis to explore and use heterogeneous electrocatalysis for cross‐coupling reactions.

High-Throughput Empirical and Virtual Screening to Discover Novel Inhibitors of Polyploid Giant Cancer Cells in Breast Cancer.

Therapy resistance in breast cancer is increasingly attributed to polyploid giant cancer cells (PGCCs), which arise through whole-genome doubling and exhibit heightened resilience to standard treatments. Characterized by enlarged nuclei and increased DNA content, these cells tend to be dormant under therapeutic stress, driving disease relapse. Despite their critical role in resistance, strategies to effectively target PGCCs are limited, largely due to the lack of high-throughput methods for assessing their viability. Traditional assays lack the sensitivity needed to detect PGCC-specific elimination, prompting the development of novel approaches. To address this challenge, we developed a high-throughput single-cell morphological analysis workflow designed to differentiate compounds that selectively inhibit non-PGCCs, PGCCs, or both. Using this method, we screened a library of 2,726 FDA Phase 1-approved drugs, identifying promising anti-PGCC candidates, including proteasome inhibitors, FOXM1, CHK, and macrocyclic lactones. Notably, RNA-Seq analysis of cells treated with the macrocyclic lactone Pyronaridine revealed AXL inhibition as a potential strategy for targeting PGCCs. Although our single-cell morphological analysis pipeline is powerful, empirically testing all existing compounds is impractical and inefficient. To overcome this limitation, we trained a machine learning model to predict anti-PGCC efficacy in silico, integrating chemical fingerprints and compound descriptions from prior publications and databases. The model demonstrated a high correlation with experimental outcomes and predicted efficacious compounds in an expanded library of over 6,000 drugs. Among the top-ranked predictions, we experimentally validated two compounds as potent PGCC inhibitors. These findings underscore the synergistic potential of integrating high-throughput empirical screening with machine learning-based virtual screening to accelerate the discovery of novel therapies, particularly for targeting therapy-resistant PGCCs in breast cancer.

Combined potential of copaifera officinalis oleoresin and chitosan against oral pathogens.

Copaifera officinalis Oleoresin (COR) and Chitosan (CH) were combined to test the potential to inhibit oral bacteria. First, COR was analyzed by GC-MS to identify its main constituents and then Minimum Inhibitory Concentration (MIC) assays and Minimum Microbiocidal Concentration (MMC) of the compounds alone against 17 pathogens were performed. Sixteen primary compounds were identified in COR, but the major constituent was β-Caryophyllene (40.5%). COR showed MIC concentrations of 26.04 to 46.87µg/mL and CH 0.1mg/mL to 0.8mg/mL. Second, the combination against oral bacteria strains was tested using a checkerboard test with the determination of Fractional Inhibitory Concentration (FIC) for synergistic effect, followed by the bacterial biofilm aggregation test using monospecies and mixed biofilm. The combination of COR and CH showed a synergistic effect for S. oralis (ATCC 10557) and an additive effect for the other strains tested, promoting bactericidal activity, as well as reducing the concentrations needed to cause bacterial inhibition. In addition, it showed good activity in inhibiting biofilm formation, with inhibition percentages close to Azithromycin. The results of this study highlight the synergistic potential of COR and CH combination as a promising strategy in the search for innovative antimicrobial therapies for infections related to oral bacterial biofilms.

Synergistic Effects of Hydroxychloride and Organic Zinc on Performance, Carcass Characteristics, Liver and Tibia Mineral Profiles of Broiler Chickens

AbstractThis study investigated the potential synergism between hydroxychloride and organic zinc (Zn) at different levels on performance and carcass characteristics of broiler chickens. There were seven experimental diets including a negative control diet without any supplemental Zn, and six diets with 80 mg/kg added Zn in the forms of ZnSO4, hydroxychloride Zn (HCZ) and organic Zn (ORZ), and a combination of HCZ and ORZ at 40 mg/kg HCZ + 40 mg/kg ORZ (HCZ40-ORZ40), 55 mg/kg HCZ + 25 mg/kg ORZ (HCZ55-ORZ25), and 70 mg/kg HCZ + 10 mg/kg ORZ (HCZ70-ORZ10). Each diet was replicated eight times with 17 chicks per replicate. On day 35, HCZ70-ORZ10 and HCZ40-ORZ40 diets resulted in the highest body weights (P &lt; 0.05). Throughout the entire production period (1–35 days), all HCZ and ORZ diets significantly improved feed conversion ratio (FCR) compared to PC (P &lt; 0.05), with HCZ40-ORZ40 showing the lowest FCR. Breast meat yield was lower in NC-fed birds, while HCZ80 and HCZ70-ORZ10 groups had the lowest abdominal fat weight (P &lt; 0.05). Liver and gizzard weight, tibia breaking strength, and ash percentage, footpad dermatitis, and hock burns were not affected. Tibia Zn content was higher in HCZ or ORZ-supplemented birds compared to NC (P &lt; 0.05), whereas other minerals in tibia and liver were unaffected. In summary, the absence of supplemental Zn negatively affects growth and carcass characteristics, whereas replacing ZnSO4 with HCZ, ORZ, or their combinations improves bodyweight and FCR. HCZ70-ORZ10 and HCZ40-ORZ40 were identified as optimal combinations for maximizing feed efficiency.

In vivo anti-tumor and anti-metastatic activity of renieramycin M and doxorubicin combination treatments on 4T1 breast cancer murine model

Breast cancer continues to be a serious global health concern, necessitating novel treatment approaches. This study explores the potential of combination therapies, investigating the combinatorial effects of doxorubicin (Dox) and renieramycin M (RM) in vivo, previously shown to have synergistic effects in vitro. Single drug administrations and combination treatments were tested on in vivo breast cancer murine models using 4T1-injected BALB/c mice. Tumor volume, animal mortality, and clinical toxicity were monitored, and in silico toxicity assessment was performed. Histopathological analyses using hematoxylin and eosin (H&amp;E) staining, and immunohistochemistry utilizing the p63 breast cancer marker were used for validation. The combination treatment of Dox and RM (5 mg/kg + 1 mg/kg) displayed a 46.53% reduction in tumor volume and an 83.63% decrease in observed metastatic infiltration in the liver. Furthermore, the combination treatment of Dox and RM significantly delayed and reduced the clinical signs of toxicity, as revealed by the decline in observed mortality as opposed to animal deaths in single drug treatments. Our study highlights the potential synergism between Dox and RM as combination therapy for breast cancer treatment. These findings provide possible strategies to improved therapies, offering a more effective and less toxic approach to mitigating breast cancer.

RNAi-mediated silencing of NlGRP3 augments the insecticidal virulence of Metarhizium anisopliae to the brown planthopper Nilaparvata lugens

The rapid development of insecticide resistance reinforces the urgent need to develop eco-friendly strategies for controlling Nilaparvata lugens (brown planthopper, BPH), the most destructive insect pest of rice. Both entomopathogens and RNA interference (RNAi) provide attractive alternatives to chemical insecticides. In this study, we demonstrated the synergistic potential of the combination use of entomopathogen- and RNAi-mediated approaches to control BPH. The β-1, 3-glucan recognition protein (βGRP) encoding gene NlGRP3 was identified and its potential role in immune defense was characterized in BPH. The open reading frame (ORF) of NlGRP3 is 1740 bp in length, encoding a 65.8 kDa protein with conserved CBM39 and GH16 domains that typically existed in the βGRP family members. NlGRP3 was shown to be differentially expressed across developmental stages and highly transcribed in the immune responsive tissues haemolymph and fat body. Topical infection with a fungal entomopathogen Metarhizium anisopliae could significantly up-regulate its expression level. RNAi-mediated silencing of NlGRP3 resulted in significantly decreased survival rate and increased susceptibility to fungal challenge in the fifth-instar BPH nymphs. The greatly enhanced mortality of NlGRP3-silenced BPH following fungal infection might be in part directly due to the immune suppression by down-regulating expressions of antimicrobial peptide genes and the imbalance of the bacterial community harboring in BPH body. Our results highly demonstrated that suppressing the insect innate immune defense through RNAi targeting the immune-related genes could effectively strengthen the biocontrol efficacy of fungal entomopathogens, providing clues to the combination use of RNAi and entomopathogens as a promising approach for BPH control.

Synergistic potential of co-millinged edible argan oil (Argania spinosa L.) and oregano leaves (Origanum vulgare L.) in food applications

By including oregano (Origanum vulgare L.) leaves (OL) during the extraction process, the nutraceutical benefits of argan oil (AO) can be significantly increased. Thanks to the employed technique (enrichment through extraction), without resorting to organic solvents. The current work aimed at developing of a green enrichment of argan oil with 2 and 5 % of OL. The purpose of this research was to evaluate the effectiveness of adding OL and its impact on AO oxidative stability under accelerated oxidation for four months. AO physicochemical characterization consisted in measuring quality indices, total phenolic contents, antioxidant activity, pigments, and sensory analysis throughout the storage period. In general, AO samples containing OL exhibited increased phenolic, chlorophylls, and carotenoid contents and lower peroxide and p-anisidine values. AO shelf-life was extended thanks to OL, which slowed down the process of lipid complete oxidation. From a sensory standpoint, a rancid taste was found in the unenriched AO, while the taste and color of oregano were more intense in the AOs supplemented with OL at 5 %. This innovative approach boost AO value in various industries and exemplifies the endless possibilities that emerge when we explore the synergy between different natural elements.