Synergistic Potential Research Articles

Synergistic potential of lopinavir and azole combinational therapy against clinically important Aspergillus species.

Aspergillus fumigatus is a widely distributed pathogen responsible for severe infections, particularly in immunocompromised individuals. Triazoles are the primary treatments options for Aspergillus infections; however, the emergence of acquired resistance to this antifungal class is becoming a growing concern. In this study, we investigated the potential of the antiviral drug, lopinavir (LPV) to restore the susceptibility of A. fumigatus strains to a set of azoles, while also reducing the required azole dosage for treatment of susceptible isolates. The combination of LPV with either itraconazole (ITC) or posaconazole (POS) demonstrated potent synergistic interactions against 16 out of 23 (~70%) and 21 out of 23 (~91%) A. fumigatus isolates, respectively. Moreover, the combination showed synergistic activity against other clinically important Aspergillus species, including A. niger, A. flavus, and A. brasiliensis. The fractional inhibitory concentration index (FICI) for the combinations ranged from 0.18 to 0.313 for ITC and 0.091 to 0.313 for POS, indicating strong synergistic effects. Further investigation revealed that efflux pump inhibition contributed to the synergy observed between azole and LPV. Morphological examination of the fungal cells subjected to this combinational therapy at sub-inhibitory doses showed the presence of carbohydrate granules/patches. The identification of LPV as a promising adjunct therapy holds promise for addressing the emerging challenge of azole resistance in Aspergillus species and improving treatment outcomes for patients.

Synergistic antimicrobial potential of essential oil nanoemulsion and ultrasound and application in food industry: A review

Essential oils such as those from clove or oregano are considered as Generally Recognized as Safe (GRAS) food ingredients and natural sanitizers to control the growth of microorganisms. However, their utilization in food industry is seriously limited since their poor water solubility and toxicological effects at high doses. Generally, appropriate preparing method to make them into nanoemulsion as sanitizers has great potential to overcome these drawbacks. As a non-thermal technology, ultrasound is able to inactivate microorganisms. And the synergistic hurdle technology of ultrasound and essential oil nanoemulsion has acquired importance within the food industry because it is reasonably effective and environmentally-friendly. This paper reviews the preparation method and physicochemical properties of plant essential oil nanoemulsion and focuses on the research progress on the synergistic antimicrobial effect of nanoemulsion and ultrasound and their application in food industry, hoping to provide further research with detailed information and potential utilization of the technique.

Immunotherapy in the Battle Against Bone Metastases: Mechanisms and Emerging Treatments

Bone metastases are a prevalent complication in advanced cancers, particularly in breast, prostate, and lung cancers, and are associated with severe skeletal-related events (SREs), including fractures, spinal cord compression, and debilitating pain. Conventional bone-targeted treatments like bisphosphonates and RANKL inhibitors (denosumab) reduce osteoclast-mediated bone resorption but do not directly impact tumor progression within the bone. This review focuses on examining the growing potential of immunotherapy in targeting the unique challenges posed by bone metastases. Even though immune checkpoint inhibitors (ICIs) have significantly changed cancer treatment, their impact on bone metastases appears limited because of the bone microenvironment’s immunosuppressive traits, which include high levels of transforming growth factor-beta (TGFβ) and the immune-suppressing cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This review underscores the investigation of combined therapeutic approaches that might ease these difficulties, such as the synergy of immune checkpoint inhibitors with agents aimed at bones (denosumab, bisphosphonates), chemotherapy, and radiotherapy, as well as the combination of immune checkpoint inhibitors with different immunotherapeutic methods, including CAR T-cell therapy. This review provides a comprehensive analysis of preclinical studies and clinical trials that show the synergistic potential of these combination approaches, which aim to both enhance immune responses and mitigate bone destruction. By offering an in-depth exploration of how these strategies can be tailored to the bone microenvironment, this review underscores the need for personalized treatment approaches. The findings emphasize the urgent need for further research into overcoming immune evasion in bone metastases, with the goal of improving patient survival and quality of life.

AI and ML-based risk assessment of chemicals: predicting carcinogenic risk from chemical-induced genomic instability

Chemical risk assessment plays a pivotal role in safeguarding public health and environmental safety by evaluating the potential hazards and risks associated with chemical exposures. In recent years, the convergence of artificial intelligence (AI), machine learning (ML), and omics technologies has revolutionized the field of chemical risk assessment, offering new insights into toxicity mechanisms, predictive modeling, and risk management strategies. This perspective review explores the synergistic potential of AI/ML and omics in deciphering clastogen-induced genomic instability for carcinogenic risk prediction. We provide an overview of key findings, challenges, and opportunities in integrating AI/ML and omics technologies for chemical risk assessment, highlighting successful applications and case studies across diverse sectors. From predicting genotoxicity and mutagenicity to elucidating molecular pathways underlying carcinogenesis, integrative approaches offer a comprehensive framework for understanding chemical exposures and mitigating associated health risks. Future perspectives for advancing chemical risk assessment and cancer prevention through data integration, advanced machine learning techniques, translational research, and policy implementation are discussed. By implementing the predictive capabilities of AI/ML and omics technologies, researchers and policymakers can enhance public health protection, inform regulatory decisions, and promote sustainable development for a healthier future.

SGLT 2 Inhibitors: Mechanisms, Clinical Applications, and Future Directions

Due to the progressive and painful nature of type 2 diabetes (T2D), treatment may require periodic evaluation of patients, intensifying glucose-lowering therapy when glycaemic targets are not achieved and testing new methods. Among the newer classes of glucose-lowering drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is), which increase urinary glucose excretion to reduce hyperglycaemia, have made an impressive entry into the T2D treatment arsenal. Given their unique insulin-independent mode of action and favourable efficacy-adverse effect profiles, and their apparent benefits on cardiovascular-renal outcomes in intermediate-high-risk T2D patients, which have led to the updating of guidelines and product monographs, the role of this drug class in multidrug regimens is promising. However, despite much speculation based on pharmacokinetic and pharmacodynamic properties, physiological rationale and potential synergism, the glycaemic and pleiotropic effects of these agents when combined with other classes of glucose-lowering drugs remain largely under-researched. Therefore, this review discusses the mechanisms, clinical applications and future therapeutic role of SGLT2 inhibitors with a review of the literature.

From biomarker discovery to combined therapies: Advancing hepatocellular carcinoma treatment strategies.

This editorial reviews advances in hepatocellular carcinoma (HCC) treatment, focusing on a triple therapy approach and biomarker discovery. Zhang et al discuss the synergistic potential of transarterial chemoembolization combined with tyrosine kinase inhibitors and PD-1 inhibitors. Meanwhile, Li et al identify protein tyrosine phosphatase non-receptor II (PTPN2) as a biomarker for poor prognosis and immune evasion in HCC. The studies highlight the importance of combined therapies and biomarkers in improving HCC treatment efficacy and patient outcomes, with PTPN2 emerging as a potential therapeutic target. This article supplements the aforementioned studies with more recent research advancements, focusing on the molecular mechanisms and clinical applications of biomarkers.

Targeting carbohydrate metabolism in colorectal cancer - synergy between DNA-damaging agents, cannabinoids, and intermittent serum starvation.

Chemotherapy is a therapy of choice for many cancers. However, it is often inefficient for long-term patient survival and is usually accompanied by multiple adverse effects. The adverse effects are mainly associated with toxicity to normal cells, frequently resulting in immune system depression, nausea, loss of appetite and metabolic changes. In this respect, the combination of chemotherapy with cannabinoids, especially non-psychoactive, such as cannabidiol, cannabinol and other minor cannabinoids, as well as terpenes, may become very useful. This is especially pertinent because the mechanisms of anticancer effects of cannabinoids on cancer cells are often different from conventional chemotherapeutics. In addition, cannabinoids help alleviate chemotherapy-induced adverse effects, regulate sleep and appetite, and are shown to have analgesic properties. Another component for achieving potential anti-cancer synergism is regulating nutrient availability and metabolism by calorie restriction and intermittent fasting in cancer cells. As tumours require a lot of energy to grow and because glucose is constantly available, malignant cells often opt to use glucose as a primary source of ATP production through substrate-level phosphorylation (fermentation) rather than through oxidative phosphorylation. Thus, periodic depletion of cancer cells of primary fuel, glucose, could result in a strong synergy in killing cancer cells by chemo- and possibly radiotherapy when combined with cannabinoids. This commentary will discuss what is known about such combinatorial treatments, including potential mechanisms and future protocols.

Immune Checkpoint Inhibitors and Vaccination: Assessing Safety, Efficacy, and Synergistic Potential.

Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients-largely developed in the context of cytotoxic therapies-becomes increasingly uncertain. Although data support the safety of combining inactivated influenza and mRNA SARS-CoV-2 vaccines with ICI therapy, comprehensive data on other infectious disease vaccines remain scarce. Notably, the combination of ICIs with infectious disease vaccines does not appear to exacerbate immune-related adverse events, despite the heightened cytokine activity observed. However, the efficacy of vaccines administered alongside ICIs in preventing infectious diseases remains poorly supported by robust evidence. Preliminary findings suggest a potential survival benefit in cancer patients receiving ICI therapy alongside influenza or SARS-CoV-2 vaccination, though the quality of evidence is currently low. Moreover, the synergistic potential of combining therapeutic cancer vaccines, particularly mRNA-based vaccines, with ICIs indicates promise but with a paucity of phase III data to confirm efficacy. This review critically examines the safety and efficacy of combining ICIs with both infectious disease vaccines and therapeutic cancer vaccines. While vaccination appears safe in patients undergoing ICI therapy, the impact on infectious disease prevention and cancer treatment outcomes warrants further rigorous investigation.

DDEL-19. DRUG-TUMOR RESIDENCE TIME DRIVES EFFICACY OF CONVECTION-ENHANCED DELIVERY IN H3 K27-ALTERED DIFFUSE MIDLINE GLIOMA

Abstract Advancements in understanding H3 K27-altered diffuse midline glioma (DMG) biology have not yet translated into effective therapies for these tumors likely due to delivery challenges across the blood-brain barrier (BBB) and variable tumor genetics. This study systematically probes convective-enhanced delivery (CED) as a means to administer small molecule drugs directly to DMG tumors, circumventing constraints imposed by the BBB. Our findings emphasize the necessity of strategic drug selection and pharmacokinetic analysis in refining CED approaches, advocating for precision medicine techniques specialized for DMG. We demonstrate that while most small molecule drugs are rapidly cleared from the brain following CED, their retention and effectiveness are substantially improved by co-administration of systemic efflux transporter (ET) inhibitors such as everolimus. The synergistic potential of combining everolimus with topotecan or ponatinib offers a novel therapeutic pathway, advocating for further investigation into this DMG management strategy.

Utilization of recycled rubber crumbs and tile powder as additives to enhance clayey soil performance

Clayey soils present challenges in engineering applications due to their inherent properties, such as low shear strength, which usually limits their use in engineering applications. Stabilization of clayey soils is crucial to enhance their performance and suitability for various purposes. Utilizing waste materials like discarded tyres and tile powder as soil stabilizers presents a sustainable solution to mitigate environmental concerns while enhancing soil properties. While previous studies have explored using either crumbled rubber or tile powder independently for soil improvement, their combined effect remained largely unexplored. This study addresses this gap by investigating the synergistic potential of blending crumbled rubber and tile powder to enhance the strength and ductility of clayey soils. A series of laboratory tests were conducted to investigate the combined effect of crumbled rubber and tile powder. First, varying percentages of crumbled rubber (2.5%, 5.0%, 7.5%, and 10%) were mixed with the soil, and standard proctor tests, California bearing ratio (CBR) tests, and unconfined compressive strength (UCS) tests were performed. Results showed optimal performance at 5.0% crumbled rubber, exhibiting the highest values for maximum dry density, CBR, and UCS. Subsequently, different percentages of tile powder (5%, 10%, 15%, and 20%) were added to the soil-rubber mixture (with 5% crumbled rubber). The addition of 15% tile powder to the 5% crumbled rubber mixture yielded the most significant improvements as maximum dry density (MDD) increased from 1.842 g/cm3 (raw soil) to 1.963 g/cm3, UCS increased from 0.5176 kg/cm2 (raw soil) to 2.606 kg/cm2, and CBR increased from 1.757% (raw soil) to 7.84%. The addition of crumbled rubber was found to shift the failure behaviour of the clayey soil from brittle to more ductile, indicating an enhanced ability to undergo deformation before failure. This study’s findings highlight the potential of combining crumbled rubber and tile powder as a sustainable solution for enhancing clayey soil properties, paving the way for further research into optimized mixture designs and expanded applications in geotechnical engineering.

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.

Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9.

Optimizing cancer treatment has become a pivotal goal in modern oncology, with advancements in immunotherapy and genetic engineering offering promising avenues. CAR-T cell therapy, a revolutionary approach that harnesses the body's own immune cells to target and destroy cancer cells, has shown remarkable success, particularly in treating acute lymphoblastic leukemia (ALL), and in treating other hematologic malignancies. While CAR-T cell therapy has shown promise, challenges such as high cost and manufacturing complexity remain. However, its efficacy in solid tumors remains limited. The integration of CRISPR/Cas9 technology, a powerful and precise genome-editing tool, also raises safety concerns regarding unintended edits and off-target effects, offers a synergistic potential to overcome these limitations. CRISPR/Cas9 can enhance CAR-T cell therapy by improving the specificity and persistence of CAR-T cells, reducing off-target effects, and engineering resistance to tumor-induced immunosuppression. This combination can also facilitate the knockout of immune checkpoint inhibitors, boosting the anti-tumor activity of CAR-T cells. Recent studies have demonstrated that CRISPR/Cas9-edited CAR-T cells can target previously untreatable cancer types, offering new hope for patients with refractory cancers. This synergistic approach not only enhances the efficacy of cancer treatment but also paves the way for personalized therapies tailored to individual genetic profiles. This review highlights the ongoing research efforts to refine this approach and explores its potential to revolutionize cancer treatment across a broader range of malignancies. As research progresses, the integration of CAR-T cell therapy and CRISPR/Cas9 holds the promise of transforming cancer treatment, making it more effective and accessible. This review explores the current advancements, challenges, and future prospects of this innovative therapeutic strategy.

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.

Impact of porin deficiency on the synergistic potential of colistin in combination with β-lactam/β-lactamase inhibitors against ESBL- and carbapenemase-producing Klebsiella pneumoniae.

Combinations of colistin and β-lactam/β-lactamase inhibitors (BLBLIs) have shown in vitro synergy against β-lactamase-producing strains. However, data are limited and conflicting, potentially attributed to variations among the examined strains. This study investigated whether loss of porins OmpK35 and OmpK36 impacts the synergistic potential of colistin in combination with ceftazidime-avibactam or meropenem-avibactam against β-lactamase-producing Klebsiella pneumoniae. Genetically modified strains were constructed by introducing blaCTX-M-15, blaKPC-2, and blaOXA-48 chromosomally into K. pneumoniae ATCC 35657, in which the major porin-encoding genes (ompK35, ompK36) were either intact or knocked out. The in vitro activity of colistin in combination with ceftazidime-avibactam or meropenem-avibactam was evaluated by time-lapse microscopy screening and in static time-kill experiments. The deletion of porins in the β-lactamase-producing strains resulted in 2- to 128-fold increases in MICs for the β-lactams and BLBLIs. The activity of avibactam was concentration-dependent, and 4- to 16-fold higher concentrations were required to achieve similar inhibition of the β-lactamases in strains with porin loss. In the screening, synergy was observed for colistin and ceftazidime-avibactam against the CTX-M-15-producing strains and colistin and meropenem-avibactam against the KPC-2- and OXA-48-producing strains. The combination effects were less pronounced in the time-kill experiments, where synergy was rarely detected. No apparent associations were found between the loss of OmpK35 and OmpK36 and combination effects with colistin and BLBLIs, indicating that additional factors determine the synergistic potential of such combinations.

Beyond Pharmacology: The Biological Mechanisms of Remote Ischemic Conditioning in Cerebrovascular Disease.

Cerebrovascular diseases (CVDs), comprising predominantly ischemic stroke and chronic cerebral hypoperfusion (CCH), are a significant threat to global health, often leading to disability and mortality. Remote ischemic conditioning (RIC) has emerged as a promising, non-pharmacological strategy to combat CVDs by leveraging the body's innate defense mechanisms. This review delves into the neuroprotective mechanisms of RIC, categorizing its effects during the acute and chronic phases of stroke recovery. It also explores the synergistic potential of RIC when combined with other therapeutic strategies, such as pharmacological treatments and physical exercise. Additionally, this review discusses the pathways through which peripheral transmission can confer central neuroprotection. This review concludes by addressing the challenges regarding and future directions for RIC, emphasizing the need for standardized protocols, biomarker identification, and expanded clinical trials to fully realize its therapeutic potential.

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.

Synergistic potentiation between P3HT and PTAA enables blade-coated carbon-electrode perovskite solar cells with >21% outdoor and >35% indoor efficiencies

P3HT is a promising hole-transport layer (HTL) for efficient and stable carbon electrode-based perovskite solar cells (C-PSCs). However, the reported low efficiencies of P3HT C-PSCs, resulting from the unmatched band alignment and electronically poor contact between perovskite and P3HT, is an obstacle. In this work, we propose a binary HTL system that incorporates PTAA into P3HT to address this issue, thereby achieving efficiencies of 21.3 % (0.04 cm2) and 18.8 % (1.0 cm2) under AM 1.5G illumination, and 35.2 % under indoor illumination of 1000 lx, all of which are the highest reported values for low-temperature printable C-PSCs. Experimental and theoretical results revealed that the performance improvements mainly stem from the following collaborative effects between P3HT and PTAA: 1) the introduction of PTAA increases more face-on orientations of P3HT as well as enhanced π–π stacking, forming more effective charge transport channels as molecular bridges; 2) the hole extraction barrier from perovskite to P3HT is reduced by 0.07 eV through incorporating PTAA; 3) triarylamine PTAA and other more face-on configurations can provide additional and stronger passivation sites, intensifying the defect passivation effects. Finally, unencapsulated P3HT-PTAA C-PSCs maintain ≈91 % of initial performance after maximum power point tracking for over 900 h.

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.

Exploring the synergistic potential: A comprehensive review of MXene-Based composite electrocatalysts

MXenes, a prominent category of 2D materials consisting of transition metal carbides, nitrides, and carbonitrides, have garnered significant interest since the introduction of Ti3C2Tx. This fascination arises from their exceptional attributes like their high special surface area, superb electrical conductivity, and remarkable mechanical strength. These qualities have established MXenes as top materials for electrocatalysis, a critical component of clean energy conversion technologies. Crucially, MXenes serve as the foundation for the next generation of electrocatalysts, aiming at high activity, selectivity, and sustainability.In electrocatalysis, MXene composites enhance the performance of various reactions, such as water splitting and fuel cell operations. When combined with metals, metal oxides, or other conductive materials, MXenes exhibit improved electrical conductivity and catalytic activity. These composites can achieve higher efficiency and selectivity in electrochemical reactions, making them suitable for sustainable energy applications. MXene composites also play an significant role in the development of supercapacitors, which are energy storage devices characterized by rapid charge and discharge capabilities. The high special surface area and excellent conductivity of MXenes increase charge storage and improve energy and power density. When MXene composites are mixed with materials such as polymers or other nanomaterials, they can further optimize these properties, leading to increased performance and longevity. Also in battery technology, MXene composites are used to improve the performance of anodes and cathodes. Their high capacity for ion storage and conduction contributes to higher energy density and faster charge/discharge rates. By combining MXenes with other materials, researchers are able to create advanced battery systems that overcome traditional limitations, resulting in batteries that are more efficient, durable, and capable of delivering higher performance. In this study MXene–Carbon composites, MXene-LDH composites, MXene-Polymer composites, MXene-MOF composites are reviewed and discussed. The versatility of MXenes is further enhanced when they are composited with various other materials. Such compositions allow for tailoring their innate properties, enabling a widespread range of applications. In terms of environmental implications, MXenes and their composites boast excellent reducibility, conductivity, and biocompatibility, making them very appropriate for use in environmental clean-up and protection applications.

Enhanced Detection of Gastrointestinal Malignancies using Machine Learning-Optimized Liquid Biopsy: A Mini Review.

Gastrointestinal (GI) cancers represent some of the most common and lethal malignancies globally, underscoring the urgent need for improved diagnostic strategies. Traditional diagnostic methods, while effective to some degree, are often invasive and unsuit-able for regular screenings. This review article explores integrating machine learning (ML) with liquid biopsy techniques as a revolutionary approach to enhance the detection and monitoring of GI cancers. Liquid biopsies offer a non-invasive alternative for cancer detection through the analysis of circulating tumor DNA (ctDNA) and other biomarkers, which when combined with ML, can significantly improve diagnostic accuracy and patient outcomes. We conducted a comprehensive review of recent advancements in liquid biopsy and ML, focusing on their synergistic potential in the early detection of GI cancers. The review addresses the application of next-generation sequencing and digital droplet PCR in enhancing the sensitivity and specificity of liquid biopsies. Machine learning algorithms have demonstrated remarkable ability in navigating complex datasets and identifying diagnostically significant patterns in ctDNA and other circu-lating biomarkers. Innovations such as machine learning-enhanced "fragmentomics" and tomographic phase imaging flow cytometry illustrate significant strides in non-invasive cancer diagnostics, offering enhanced detection capabilities with high accuracy. The integration of ML in liquid biopsy represents a transformative step in the early detection and personalized treatment of GI cancers. Future research should focus on overcoming current limitations, such as the heterogeneity of tumor-derived genetic materials and the standardization of liquid biopsy protocols, to fully realize the potential of this technol-ogy in clinical settings.