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Introduction: The Prunella vulgaris L. (PVL) and Taraxacum mongolicum Hand.-Mazz. (TH) herb pair, which is commonly used in traditional Chinese medicine (TCM), has been applied for the treatment of breast cancer. Although its efficacy is validated, the synergistic anti-breast cancer compound combinations within this herb pair and their underlying mechanisms of action remain unclear. Methods: This study aimed to identify and validate synergistic anti-breast cancer compound combinations within the PVL-TH pair using large-scale biomedical data, artificial intelligence and experimental methods. The first step was to investigate the anti-breast cancer effects of various PVL and TH extracts using in vitro cellular assays to identify the most effective superior extracts. These superior extracts were subjected to liquid chromatography-mass spectrometry (LC-MS) analysis to identify their constituent compounds. A deep learning-based prediction model, DeepMDS, was applied to predict synergistic anti-breast cancer multi-compound combinations. These predicted combinations were experimentally validated for their anti-breast cancer effects at actual content ratios found in the extracts. Preliminary bioinformatics analyses were conducted to explore the mechanisms of action of these superior combinations. We also compared the anti-breast cancer effects of superior extracts from different geographical origins and analyzed the contents of compounds to assess their representation of the anti-tumor effect of the corresponding TCM. Results: The results revealed that LC-MS analysis identified 27 and 21 compounds in the superior extracts (50% ethanol extracts) of PVL and TH, respectively. Based on these compounds, DeepMDS model predicted synergistic anti-breast cancer compound combinations such as F973 (caffeic acid, rosmarinic acid, p-coumaric acid, and esculetin), T271 (chlorogenic acid, cichoric acid, and caffeic acid), and T1685 (chlorogenic acid, rosmarinic acid, and scopoletin) from single PVL, single TH and PVL-TH herb pair, respectively. These combinations, at their actual concentrations in extracts, demonstrated superior anti-breast cancer activity compared to the corresponding extracts. The bioinformatics analysis revealed that these compounds could regulate tumor-related pathways synergistically, inhibiting tumor cell growth, inducing cell apoptosis, and blocking cell cycle progression. Furthermore, the concentration ratio and total content of compounds in F973 and T271 were closely associated with their anti-breast cancer effects in extracts from various geographical origins. The compound combination T1685 could represent the synergistic anti-breast cancer effects of the PVL-TH pair. Discussion: This study provides insights into exploring the representative synergistic anti-breast cancer compound combinations within the complex TCM. [ABSTRACT FROM AUTHOR]

In this work, an electrochemical system combined with low-cost UV-LEDs was implemented for the inactivation of Escherichia coli and Pseudomonas aeruginosa. The individual elimination of these bacteria was followed by plate counting and flow cytometry, as complementary techniques to establish the cell inactivation and non-viability, respectively. The contribution of the different parts of the disinfection system (anode, cathode, and light) was determined. In addition, the efficiency of the UV-LEDs/GDE/DSA system in the disinfection of an irrigation water sample was studied. It was found that the combination of the electrochemical system with UV-LEDs was highly synergistic (φ > 7), having low electric energy consumptions per order of magnitude (EEO: 1.13 × 10–2 and 1.55 × 10–2 kWh/m3 order). Moreover, some differences in the inactivation kinetics and synergy between E. coli and P. aeruginosa were observed and linked to the structural/morphological characteristics of the two bacteria. Remarkably, the electrochemical system combined with low-cost UV-LEDs inactivated both target microorganisms after only 2 min of treatment. The flow cytometry analyses evidenced the damage to the cell membrane of the bacteria by the simultaneous and synergistic action of the electrogenerated H2O2 and active chlorine species (ACS), plus the attacks of photo-generated reactive oxygen species. This synergistic combination in the UV-LEDs/GDE/DSA system demonstrated remarkable efficiency in the disinfection of an irrigation water sample, achieving the elimination of culturable bacteria in 45 min of treatment. The results of this research demonstrated the capacity and great potential of an easy combination of electrochemistry with UV-LEDs as an alternative system for the elimination of gram-negative bacteria in water. [ABSTRACT FROM AUTHOR]

IntroductionThe Prunella vulgaris L. (PVL) and Taraxacum mongolicum Hand.-Mazz. (TH) herb pair, which is commonly used in traditional Chinese medicine (TCM), has been applied for the treatment of breast cancer. Although its efficacy is validated, the synergistic anti-breast cancer compound combinations within this herb pair and their underlying mechanisms of action remain unclear.MethodsThis study aimed to identify and validate synergistic anti-breast cancer compound combinations within the PVL-TH pair using large-scale biomedical data, artificial intelligence and experimental methods. The first step was to investigate the anti-breast cancer effects of various PVL and TH extracts using in vitro cellular assays to identify the most effective superior extracts. These superior extracts were subjected to liquid chromatography-mass spectrometry (LC-MS) analysis to identify their constituent compounds. A deep learning-based prediction model, DeepMDS, was applied to predict synergistic anti-breast cancer multi-compound combinations. These predicted combinations were experimentally validated for their anti-breast cancer effects at actual content ratios found in the extracts. Preliminary bioinformatics analyses were conducted to explore the mechanisms of action of these superior combinations. We also compared the anti-breast cancer effects of superior extracts from different geographical origins and analyzed the contents of compounds to assess their representation of the anti-tumor effect of the corresponding TCM.ResultsThe results revealed that LC-MS analysis identified 27 and 21 compounds in the superior extracts (50% ethanol extracts) of PVL and TH, respectively. Based on these compounds, DeepMDS model predicted synergistic anti-breast cancer compound combinations such as F973 (caffeic acid, rosmarinic acid, p-coumaric acid, and esculetin), T271 (chlorogenic acid, cichoric acid, and caffeic acid), and T1685 (chlorogenic acid, rosmarinic acid, and scopoletin) from single PVL, single TH and PVL-TH herb pair, respectively. These combinations, at their actual concentrations in extracts, demonstrated superior anti-breast cancer activity compared to the corresponding extracts. The bioinformatics analysis revealed that these compounds could regulate tumor-related pathways synergistically, inhibiting tumor cell growth, inducing cell apoptosis, and blocking cell cycle progression. Furthermore, the concentration ratio and total content of compounds in F973 and T271 were closely associated with their anti-breast cancer effects in extracts from various geographical origins. The compound combination T1685 could represent the synergistic anti-breast cancer effects of the PVL-TH pair.DiscussionThis study provides insights into exploring the representative synergistic anti-breast cancer compound combinations within the complex TCM.

Glioblastoma is a fast-growing and aggressive brain tumor. Despite the current treatment methods, such as chemical and surgical operations, the prognosis is still poor. Therefore, combined therapeutic strategies are proposed to maximize therapeutic efficacy and reduce toxicity. Thymoquinone has been shown to have neuroprotective effects in addition to its anti-cancer effects on different types of cancer. 5-Fluorouracil, on the other hand, is a cytotoxic chemotherapy agent used to treat cancer. As a synergistic combinational approach, this study aimed to examine the antiproliferative effects and production of reactive oxygen species in a glioblastoma cell line.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a severe threat to public health. Antimicrobial peptides (AMPs) are novel and potential antimicrobials with specific antibacterial mechanisms. Our aim was to study the potential of LL37, FK16, and FK13 to enhance the anti-MRSA activity of antibiotics in vitro, particularly penicillin G and ampicillin. Our results showed that FK16 and FK13 have more synergistic inhibitory effects to MRSA strains when combined with penicillin G and ampicillin. In addition, AMPs exhibited strong membrane permeabilizing properties, and membrane permeabilizing effects can provide a possible explanation for the improved antibacterial effects of antibiotics, since permeabilizing AMPs have the potential to increase the access of antibiotics. To further study the electrostatic interactions among cationic AMPs with negatively charged bacteria, we measured the zeta potentials of three MRSA strains and also neutralized three MRSA strains with the addition of cationic AMPs. Further, we demonstrated the connection between membrane permeabilization and zeta potential neutralization. Finally, we treated MRSA strains with AMPs and characterized the MICs of penicillin G and ampicillin. FK16 was the most promising AMP among the three AMPs, since exposure to FK16 decreased the MICs of both penicillin G and ampicillin for all MRSA strains and also demonstrated more synergistic combinations when combined with antibiotics. AMP exposure and subsequent membrane permeabilization provide a possible pathway to re-sensitize drug-resistant bacteria to traditional antibiotics. Re-sensitization may help preserve the effectiveness of traditional antibiotics, thus providing a potential new strategy for fighting MRSA infections. [ABSTRACT FROM AUTHOR]

Background: Tisanes are a potential source of phytochemicals to reduce disease risk conditions and are used to protect from non-communicable diseases, globally. A few tisanes have gained more popularity than others depending on their chemical composition based on the geographical origin of the used herb. Several Indian tisanes have been claimed to have traits beneficial to people with or at a high risk of type 2 diabetes mellitus. Under the concept, the literature was reviewed and compiled into a document to highlight the chemical uniqueness of popular Indian traditional tisanes to be more informative and potent as per modern medicine to overcome type 2 diabetes mellitus. Methods: An extensive literature survey was conducted using computerized database search engines, such as Google Scholar, PubMed, ScienceDirect, and EMBASE (Excerpta Medica database) for herbs that have been described for hyperglycemia, and involved reaction mechanism, in-vivo studies as well as clinical efficacies published since 2001 onwards using certain keywords. Compiled survey data used to make this review and all findings on Indian traditional antidiabetic tisanes are tabulated here. Results: Tisanes render oxidative stress, counter the damage by overexposure of free radicals to the body, affect enzymatic activities, enhance insulin secretion, etc. The active molecules of tisanes also act as anti-allergic, antibacterial, anti-inflammatory, antioxidant, antithrombotic, antiviral, antimutagenicity, anti-carcinogenicity, antiaging effects, etc. WHO also has a strategy to capitalize on the use of herbals to keep populations healthy through effective and affordable alternative means with robust quality assurance and strict adherence to the product specification.

Background: Cytokine storm syndrome (CSS) is a leading cause of morbidity and mortality in patients with late-stage coronavirus disease 2019 (COVID-19), causing multiple organ failure and death. According to prior research, fraxin, and quercetin have anti-inflammatory, antioxidant, antimicrobial, and antiviral properties. Therefore, this study aimed to investigate the anti-cytokine storm activity of fraxin and quercetin, their combination, and the molecular mechanism behind this activity in Lipopolysaccharide (LPS)-induced RAW 264.7 cells. Methods: LPS-induced macrophage cells were treated with fraxin, quercetin, or their combinations at various doses for cytotoxicity, anti-cytokine assays, and gene expression analyses. An enzyme-linked immunosorbent assay was used to quantify the levels of proinflammatory cytokines, interleukin 1 beta (IL1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), and RT-PCR was used to measure the gene expression of PPAR-γ and Toll-like receptor 4 (TLR-4) concerning GAPDH as a reference gene. Results: The results revealed a slight decrease in cell viability only when higher concentrations were applied to the cells. Fraxin, quercetin, and their combination reduced the generation of proinflammatory cytokines. The combination (fraxin + quercetin (FQ)) reduced the levels of IL-1β, IL-6, and TNF-α by 56.2%, 58.5%, and 70.6% respectively, compared to the LPS-only control; pretreatment of cells with farxin, quercetin, and their combination resulted in significant inhibition of TLR-4 gene expression by 89%, 82%, and 93% respectively, compared to the control (P˂ 0.05); FQ upregulated PPAR-γ expression up to 60-fold compared to the control, while fraxin and quercetin increased PPAR-γ by 17.6 and 8.6-folds, respectively. Conclusions: Based on these findings, fraxin, quercetin and their combination might be considered anti-cytokine storm agents, which could lay the groundwork for future research into other combinations of fraxin and quercetin, as well as the pathways involved in the molecular mechanisms underlying the synergistic anti-cytokine-storm-activity.

Background: Combination antifungal therapy has become a prominent approach in medical practice as it takes advantage of synergistic interactions by interfering with multiple targets of the pathogen, broadening the spectrum of activity, reducing the development of resistance, and improving treatment outcomes. Therefore, combining conventional antifungal drugs with natural products can increase antifungal activity, reduce side effects, and optimize therapeutic effects. Purpose: The present study aimed to evaluate the antifungal activity of thyme essential oil (ThyEO) in combination with amphotericin B, caspofungin, fluconazole, itraconazole, and posaconazole (PSZ), as well as its inhibitory effect on Candida albicans virulence factors. Materials and Methods: The microbroth dilution assay was employed to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Interactions were assessed using the microdilution checkerboard assay. Ergosterol and methylene blue assays were used to detect effects on fungal membrane, while the sorbitol assay was used to detect effects on fungal cell wall. Inhibition of yeast virulence factors (adherence to epithelial cells, germ tube and pseudomycelium formation, secretion of hydrolytic enzymes, and biofilm formation) was assessed with previously reported methods. Results: Almost all combinations showed additivism against C. albicans, except ThyEO/PSZ (31.25/0.0039 µg/ml), which showed partial synergism. Furthermore, all mixtures were fungicidal against C. albicans strains. ThyEO/PSZ, its components alone, and thymol were shown to disrupt the fungal cytoplasmic membrane, increasing its permeability. ThyEO/PSZ, at sub-inhibitory concentrations, significantly decreased the ability of C. albicans to adhere to buccal epithelial cells. ThyEO/PSZ, ThyEO, and PSZ were able to reduce the pseudomycelium production of C. albicans while thymol completely inhibited its formation. ThyEO/PSZ, each combination component on its own, and thymol inhibited biofilm formation and preformed biofilm of C. albicans. Notably, ThyEO/PSZ showed synergistic and fungicidal activity against a resistant strain of C. albicans, reducing the PSZ dose by 4-fold. Conclusion: These findings make ThyEO and ThyEO/PSZ mixture valuable candidates for the development of alternative antifungals with a lower incidence of adverse effects.

Tisanes are a potential source of phytochemicals to reduce disease risk conditions and are used to protect from non-communicable diseases, globally. A few tisanes have gained more popularity than others depending on their chemical composition based on the geographical origin of the used herb. Several Indian tisanes have been claimed to have traits beneficial to people with or at a high risk of type 2 diabetes mellitus. Under the concept, the literature was reviewed and compiled into a document to highlight the chemical uniqueness of popular Indian traditional tisanes to be more informative and potent as per modern medicine to overcome type 2 diabetes mellitus. An extensive literature survey was conducted using computerized database search engines, such as Google Scholar, PubMed, ScienceDirect, and EMBASE (Excerpta Medica database) for herbs that have been described for hyperglycemia, and involved reaction mechanism, in-vivo studies as well as clinical efficacies published since 2001 onwards using certain keywords. Compiled survey data used to make this review and all findings on Indian traditional antidiabetic tisanes are tabulated here. Tisanes render oxidative stress, counter the damage by overexposure of free radicals to the body, affect enzymatic activities, enhance insulin secretion, etc. The active molecules of tisanes also act as anti-allergic, antibacterial, anti-inflammatory, antioxidant, antithrombotic, antiviral, antimutagenicity, anti-carcinogenicity, antiaging effects, etc. WHO also has a strategy to capitalize on the use of herbals to keep populations healthy through effective and affordable alternative means with robust quality assurance and strict adherence to the product specification. [ABSTRACT FROM AUTHOR]

Oral nanomedicines present a preferable avenue for cancer immunotherapy, but their efficacy is limited by gastrointestinal absorption challenges, tumor physiopathologic barriers, and immune evasion mechanisms. Here, we present an approach that combines an oral transcytotic doxorubicin (DOX) nanomedicine with the histone demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX1), thereby enabling synergistic chemoimmunotherapy. We demonstrate that IOX1 significantly augments the transcytosis capabilities of DOX-loaded poly(2-( N -oxide- N , N -diethylamino)ethylmethacrylate)-poly(ε-caprolactone) micelles (OPDOX), promoting their transcellular transport across various cellular barriers (villus, endothelial, and tumor cells), thus improving oral adsorption, vascular extravasation, and tumor penetration. Furthermore, IOX1 sensitizes chemotherapy to potentiate DOX-induced immunogenic cell death and downregulates programmed cell death-ligand 1 to disrupt the immune checkpoint mechanism, synergistically boosting robust antitumor immune responses. Consequently, orally administered OPDOX in combination with IOX1 efficiently inhibits CT26 tumor growth, highlighting the significant potential for enhancing the efficacy of oral nanomedicines in cancer chemoimmunotherapy.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a severe threat to public health. Antimicrobial peptides (AMPs) are novel and potential antimicrobials with specific antibacterial mechanisms. Our aim was to study the potential of LL37, FK16, and FK13 to enhance the anti-MRSA activity of antibiotics in vitro, particularly penicillin G and ampicillin. Our results showed that FK16 and FK13 have more synergistic inhibitory effects to MRSA strains when combined with penicillin G and ampicillin. In addition, AMPs exhibited strong membrane permeabilizing properties, and membrane permeabilizing effects can provide a possible explanation for the improved antibacterial effects of antibiotics, since permeabilizing AMPs have the potential to increase the access of antibiotics. To further study the electrostatic interactions among cationic AMPs with negatively charged bacteria, we measured the zeta potentials of three MRSA strains and also neutralized three MRSA strains with the addition of cationic AMPs. Further, we demonstrated the connection between membrane permeabilization and zeta potential neutralization. Finally, we treated MRSA strains with AMPs and characterized the MICs of penicillin G and ampicillin. FK16 was the most promising AMP among the three AMPs, since exposure to FK16 decreased the MICs of both penicillin G and ampicillin for all MRSA strains and also demonstrated more synergistic combinations when combined with antibiotics. AMP exposure and subsequent membrane permeabilization provide a possible pathway to re-sensitize drug-resistant bacteria to traditional antibiotics. Re-sensitization may help preserve the effectiveness of traditional antibiotics, thus providing a potential new strategy for fighting MRSA infections.

Abstract This study aimed to evaluate the effect of duloxetine hydrochloride (DH) on Cryptococcus neoformans. DH minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were 18.5 µg/mL, and the combination with fluconazole (FLZ) reduced the MIC value by 16-and 4-fold for DH and FLZ, respectively. The capsule size decreased by 67% and 16% when treated with DH and DH with FLZ, respectively. Therefore, this study showed that DH is active against C. neoformans alone and in combination with FLZ, leading to the reduction of the capsule size of this yeast.

Introduction: This review aims to comprehensively assess the collective findings in the realm of cancer therapy, focusing on the integration of nanomaterial - based radiosensitizers in combined photothermal and radiotherapy. The study delves into the potential of high atomic number (Z) nanomaterials, including gold, platinum, titanium, and hafnium nanoparticles, to enhance treatment outcomes through a synergistic approach. Methods: A literature review was conducted to identify relevant studies investigating the use of high - Z nanomaterials in combined cancer therapy. Emphasis was placed on studies reporting on the efficacy of these sensitizers in overcoming radiotherapy challenges, with a particular focus on radioresistance of hypoxic tumor cells. Data extraction included in vitro and in vivo outcomes, such as cell viability, reactive oxygen species production, double - strand breaks, apoptosis, and tumor growth inhibition. Biocompatibility and potential clinical applications of high - Z nanomaterials were also assessed. Results: Studies reveal a consistent and substantial decrease in cell viability in in vitro studies employing high - Z nanomaterials in combination therapy, surpassing the effects of standalone radiotherapy or photothermal therapy. Noteworthy increases in reactive oxygen species production, induction of double - strand breaks, and apoptosis further underscore the radiosensitizing potential of these materials. In vivo studies consistently demonstrate superior inhibitory effects on tumor growth with combination therapy, establishing its superiority over individual modalities. Additionally, the results of studies confirm the excellent biocompatibility of high - Z nanomaterials, supporting their potential for clinical translation. Conclusions: This review provides compelling evidence for the integration of nanomaterial radiosensitizers into combined cancer photothermal therapy and radiotherapy. The precision offered by targeted hyperthermia and radiation sensitization holds significant promise for improving treatment outcomes while minimizing side effects. The synthesized data strongly advocate for the continued exploration of high - Z nanomaterials in clinical settings, emphasizing their potential to revolutionize cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Nanoparticle-aided combination chemotherapy offers several advantages like ratiometric drug delivery, dose reduction, multi-targeted therapy, synergism, and overcoming multi-drug resistance. The current research was instigated to facilitate targeted and ratiometric co-delivery of docetaxel (DT) and curcumin (CR) through the development of folate (FA)–appended nanostructured lipid carriers (NLCs), i.e., FA-DTCR-NLCs to lung cancer cells. The FA-DTCR-NLCs were formulated by employing a scaleable and solvent-free high-pressure homogenization approach. The FA-DTCR-NLCs were evaluated for in vitro and in vivo characteristics using suitable analytical and statistical techniques. The FA-DTCR-NLCs demonstrated physicochemical properties and particokinetics suitable for targeted, ratiometric co-delivery of the anticancer agents. This was further affirmed by significantly better in vivo relative bioavailability of DT (24.85 fold) with FA-DTCR-NLCs as compared with Taxotere® (p < 0.05) and cell line studies. A significant tumor regression was observed from the results of tumor staging in a murine model of lung carcinoma (p < 0.05). Immunostaining of the tumor sections with tumor differentiation biomarkers suggested considerably higher apoptotic, anti-proliferative, anti-angiogenic, and anti-metastatic potential of FA-DTCR-NLCs compared with Taxotere®. In vivo toxicity assessment of the FA-DTCR-NLCs demonstrated a noteworthy reduction in DT associated side effects. The in vitro and in vivo pre-clinical findings prove the therapeutic and safety pre-eminence of FA-DTCR-NLCs for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Huperzia serrata (Thunb.) Trevis is widely used in traditional asiatic medicine to treat many central disorders including, schizophrenia, cognitive dysfunction, and dementia. The major alkaloid, Huperzine A (HA), of H. serrata is a well-known competitive reversible inhibitor of acetylcholinesterase (AChE) with neuroprotective effects. Inspired by the tradition, we developed a green one-step method using microwave assisted extraction to generate an extract of H. serrata , called NSP01. This green extract conserves original neuropharmacological activity and chemical profile of traditional extract. The neuroprotective activity of NSP01 is based on a precise combination of three major constituents: HA and two phenolic acids, caffeic acid (CA) and ferulic acid (FA). We show that CA and FA potentiate HA-mediated neuroprotective activity. Importantly, the combination of HA with CA and FA does not potentiate the AChE inhibitory property of HA which is responsible for its adverse side effects. Collectively, these experimental findings demonstrated that NSP01, is a very promising plant extract for the prevention of Alzheimer's disease and memory deficits. [ABSTRACT FROM AUTHOR]

Lithium-sulfur batteries (LSBs) have become one of the most competitive candidates for next generation energy storage systems due to the high theoretical energy density, nevertheless, the severe shuttle effect, volume expansion, and poor electrical conductivity restrict their practical application. Herein, we report a synergistic combination of 3D carbon matrix (CdS@NG-CNT) composed of low-defect carbon nanotubes (CNTs) and nitrogen-doped graphene (NG) decorated with low loading of cadmium sulfide quantum dots as sulfur host and carbon black (CB) as separator layer to collectively solve these issues. Specifically, the developed host material possesses abundant macropores and mesopores and high electrical conductivity, which endow the carbon matrix multifaceted structural properties for polysulfides immobilization, electrons/Li+ transfer, and Li2S formation, as well as buffering the volume expansion during cycling. The CB-modified separator can help to enhance the interconversion of intercepted polysulfides. Benefiting from these aspects, the cell equipped with CdS@NGCNT/S//CB-PP exhibits a superior rate capacity of 1493.6 mAh/g at 0.2 C (1st), and maintains a capacity of 479.7 mAh/g after 1050 cycles with an ultralow capacity decay rate of 0.051% at 1.0 C. This work provides a useful strategy to solve issues of the current LSBs, which may practically be used in the high-energy density. [ABSTRACT FROM AUTHOR]

Shexiang Baoxin Pill (SBP) is an oral formulation of Chinese materia medica for the treatment of angina pectoris. It displays pleiotropic roles in protecting the cardiovascular system. However, the mode of action of SBP in promoting angiogenesis, and in particular the synergy between its constituents is currently not fully understood. The combination of ginsenosides Rb2 and Rg3 were studied in human umbilical vein endothelial cells (HUVECs) for their proangiogenic effects. To understand the mode of action of the combination in more mechanistic detail, RNA-Seq analysis was conducted, and differentially expressed genes (DEGs), pathway analysis and Weighted Gene Correlation Network Analysis (WGCNA) were applied to further identify important genes that a play pivotal role in the combination treatment. The effects of pathway-specific inhibitors were observed to provide further support for the hypothesized mode of action of the combination. Ginsenosides Rb2 and Rg3 synergistically promoted HUVEC proliferation and tube formation under defined culture conditions. Also, the combination of Rb2/Rg3 rescued cells from homocysteine-induced damage. mRNA expression of CXCL8, CYR61, FGF16 and FGFRL1 was significantly elevated by the Rb2/Rg3 treatment, and representative signaling pathways induced by these genes were found. The increase of protein levels of phosphorylated-Akt and ERK42/44 by the Rb2/Rg3 combination supports the notion that it promotes endothelial cell proliferation via the PI3K/Akt and MAPK/ERK signaling pathways. The present study provides the hypothesis that SBP, via ginsenosides Rb2 and Rg3, involves the CXCR1/2 CXCL8 (IL8)-mediated PI3K/Akt and MAPK/ERK signaling pathways in achieving its proangiogenic effects.

Background. The bio-preservation of food products using various natural ingredients and metabolites from various types of beneficial microorganisms released during targeted fermentation is a method that simultaneously has a preservative effect on the food product and provides a model of its composition in order to ensure its functional and health properties. This double effect can be achieved by incorporating ingredients with proven preservative and functional effects into the food product, such as essential oils from various plant species and probiotic bacteria. The aim of the present research was to study the synergistic effect of selected probiotic lactic acid bacteria (LAB) and essential oils with high antimicrobial activity against pathogenic and spoilage microorganisms for the bio-preservation of chocolate mousse food emulsion. Materials and methods. The susceptibility of the selected probiotic strain Lactobacillus plantarum D2 to different concentrations of the selected lemon or grapefruit essential oil was examined using the disc-diffusion method. Nine chocolate mousse variants were prepared with the inclusion of free or immobilized cells of the probiotic strain L. plantarum D2 and/or lemon or grapefruit zest essential oils. The chocolate mousse variants were stored for 20 days in refrigerated conditions, and changes in the concentration of viable lactobacilli cells, the pH and the microbiological purity were monitored in accordance with standard requirements by taking samples on the 0th, 5th, 10th, 15th, and 20th days of storage. An organoleptic evaluation of the chocolate variants was performed on the 0th day. Results. Concentrations of up to 1% lemon or grapefruit essential oil did not affect the growth of the probiotic strain L. plantarum D2, which revealed opportunities for their joint application for the bio-preservation of food emulsions. The obtained chocolate mousse variants were characterized by preserved organoleptic characteristics and microbiological safety. Free or immobilized probiotic L. plantarum D2 cells applied alone or in combination with lemon or grapefruit essential oils provided bio-preservation of the food emulsions, maintaining a high concentration of viable cells (106-107 cfu/g) during storage under refrigerated conditions for 20 days. Conclusion. The combined application of free or immobilized probiotic LAB and lemon or grapefruit essential oils resulted in better bio-preservation results than in the use of probiotic LAB or essential oils alone, thus suggesting a synergistic effect between the two bio-preservative agents. Moreover, the obtained chocolate mousse emulsions can be classified as functional foods and the chocolate mousse food matrix can successfully be used as a vehicle for delivery of probiotic LAB to a wide range of food consumers. The obtained results and the developed successful bio-preservation strategy for the production of chocolate mousse food emulsions would provide grounds for the future selection of other probiotic lactobacilli strains, essential oils and synergistic combinations of them for the development of successful bio-preservation strategies for other types of food and beverage products. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitors represent an encouraging class of antitumor drugs. HDAC inhibitors induce a series of molecular and biological responses and minimal toxicity to normal cells. Citarinostat (Acy-241) is a second generation, orally administered, HDAC6-selective inhibitor. Momelotinib (CYT387) is an orally administered inhibitor of Janus kinase/signal transducer of transcription-3 (JAK/STAT3) signaling. Momelotinib showed efficacy in patients with myelofibrosis. We hypothesized that both HDAC and JAK/STAT pathways were important in lymphoproliferative disorders, and that inhibiting JAK/STAT3 and HDAC simultaneously might enhance the efficacy of momelotinib and citarinostat without increasing toxicity. Accordingly, we tested the citarinostat + momelotinib combination in lymphoid cell lines. Citarinostat + momelotinib showed strong cytotoxicity; it significantly reduced mitochondrial membrane potential, down-regulated Bcl-2 and Bcl-xL, and activated caspases 9 and 3. Caspase-8 was upregulated in only two lymphoid cell lines, which indicated activation of the extrinsic apoptotic pathway. We identified a lymphoid cell line that was only slightly sensitive to the combination treatment. We knocked down thioredoxin expression by transfecting with small interfering RNA that targeted thioredoxin. This knockdown increased cell sensitivity to the combination-induced cell death. The combination treatment reduced Bcl-2 expression, activated caspase 3, and significantly inhibited cell viability and clonogenic survival. [ABSTRACT FROM AUTHOR]

The present paper continues a more complex research related to the increased synergism in terms of both anti-inflammatory and analgesic effect obtained by the addition of chlorpheniramine (CLF) to the common acetylsalicylic acid (ASA), acetaminophen (PAR), and caffeine (CAF) combination. This synergistic effect was previously highlighted both in vitro in rat models and in vivo in the treatment of migraine. The aim of the research was to further evaluate the analgesic effect of a synergistic low-dose ASA–PAR–CAF–CLF combination in the treatment of low back pain, in a parallel, multiple-dose, double-blind, active controlled clinical trial. A number of 89 patients with low back pain of at least moderate intensity were randomly assigned to receive Algopirin® (ALG), a combinational product containing 125 mg ASA, 75 mg PAR, 15 mg CAF, and 2 mg CLF, or PAR 500 mg, a drug recognized by American Pain Society as “safe and effective” in the treatment of low back pain. One tablet of the assigned product was administered three times a day for seven consecutive days. The patients evaluated their pain level using a Visual Analog Scale prior to administration, and at 1, 2, 4, and 6 h after the morning dose. Time course of effect was similar in structure and size for both treatments. Pain relief appeared rapidly and steadily increased over 4 h after drug administration. Differential pain curves of ALG and PAR were very similar and comparable with the previously determined ALG analgesia pattern in migraine. Differences between the daily mean pain scores were not statistically significant for the two treatments. Similar results were obtained for the Sum of Pain Intensity Differences (SPID) for 0–4 h and 0–6 h intervals as well as for the time course of the proportion of patients with at least 30% and at least 50% pain relief. In conclusion, in spite of very small doses of active components, ALG proved equally effective to the standard low back pain treatment and therefore a viable therapeutic alternative, mainly for patients with gastrointestinal and hepatic sensitivity.Trial Registration:www.ClinicalTrials.gov, identifier EudraCT No.: 2015–002314–74.

The ability of bacteria to form biofilms hinders any conventional treatment for chronic infections and has serious socio-economic implications. For this purpose, a nanocarrier capable of overcoming the barrier of the mucopolysaccharide matrix of the biofilm and releasing its loaded-antibiotic within this matrix would be desirable. Herein, we developed a new nanosystem based on levofloxacin (LEVO)-loaded mesoporous silica nanoparticles (MSN) decorated with the lectin concanavalin A (ConA). The presence of ConA promotes the internalization of this nanosystem into the biofilm matrix, which increases the antimicrobial efficacy of the antibiotic hosted within the mesopores. This nanodevice is envisioned as a promising alternative to conventional treatments for infection by improving the antimicrobial efficacy and reducing side effects. The present study is focused on finding an adequate therapeutic solution for the treatment of bone infection using nanocarriers that are capable of overcoming the biofilm barrier by increasing the therapeutic efficacy of the loaded antibiotic. For this purpose, we present a nanoantibiotic that increases the effectiveness of levofloxacin to destroy the biofilm formed by the model bacterium E. coli. This work opens new lines of research in the treatment of chronic infections based on nanomedicines. [ABSTRACT FROM AUTHOR]

The present paper continues a more complex research related to the increased synergism in terms of both anti-inflammatory and analgesic effect obtained by the addition of chlorpheniramine (CLF) to the common acetylsalicylic acid (ASA), acetaminophen (PAR), and caffeine (CAF) combination. This synergistic effect was previously highlighted both in vitro in rat models and in vivo in the treatment of migraine. The aim of the research was to further evaluate the analgesic effect of a synergistic low-dose ASA–PAR–CAF–CLF combination in the treatment of low back pain, in a parallel, multiple-dose, double-blind, active controlled clinical trial. A number of 89 patients with low back pain of at least moderate intensity were randomly assigned to receive Algopirin® (ALG), a combinational product containing 125 mg ASA, 75 mg PAR, 15 mg CAF, and 2 mg CLF, or PAR 500 mg, a drug recognized by American Pain Society as "safe and effective" in the treatment of low back pain. One tablet of the assigned product was administered three times a day for seven consecutive days. The patients evaluated their pain level using a Visual Analog Scale prior to administration, and at 1, 2, 4, and 6 h after the morning dose. Time course of effect was similar in structure and size for both treatments. Pain relief appeared rapidly and steadily increased over 4 h after drug administration. Differential pain curves of ALG and PAR were very similar and comparable with the previously determined ALG analgesia pattern in migraine. Differences between the daily mean pain scores were not statistically significant for the two treatments. Similar results were obtained for the Sum of Pain Intensity Differences (SPID) for 0–4 h and 0–6 h intervals as well as for the time course of the proportion of patients with at least 30% and at least 50% pain relief. In conclusion, in spite of very small doses of active components, ALG proved equally effective to the standard low back pain treatment and therefore a viable therapeutic alternative, mainly for patients with gastrointestinal and hepatic sensitivity. Trial Registration: www.ClinicalTrials.gov , identifier EudraCT No.: 2015–002314–74. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Ni-containing mixed oxide catalysts were employed for steam oxidative cracking. • Strong metal-support interactions increased Ni metallic and oxygen vacant sites. • Ni-containing catalysts preferred steam oxidative cracking route to steam reforming. • Steam oxidative cracking was enhanced by combination of hydrogenation and oxidation. • Enhancement of steam oxidative cracking resulted in high liquid yield in the process. Abstract Steam oxidative cracking route of 1-methyl naphthalene were investigated through the combination of oxidation and hydrogenation over nickel-containing mixed oxide catalysts. Depending on the used supports, several types of active sites for oxidation, hydrogenation, and steam decomposition were generated by various metal–support and support–support interactions. The steam reforming routes were dominant without nickel, resulting in high carbon selectivity of gas due to a full-cracking process. With nickel, steam oxidative cracking routes were strongly enhanced by a synergistic combination between hydrogenation occurring on the Ni metallic sites and oxidation over mobile lattice oxygens in a Ce x Zr 1-x O 2 solid solution, resulting to the higher carbon selectivity of liquid products than that of gas products. Among the prepared catalysts, optimal interaction between Ni and ceria-zirconia-alumina mixed oxide support caused not only an increase of oxygen vacancies in solid solutions, but also the formation of smaller Ni metallic nanoparticles, resulting in reinforcement of steam oxidative cracking of 1-methylnaphthanlene. [ABSTRACT FROM AUTHOR]

Recent development has enabled synergistic drugs in treating a wide range of cancers. Being highly context-dependent, however, identification of successful ones often requires screening of combinational dose on different testing platforms in order to gain the best anticancer effects. To facilitate the development of effective computational models, we reviewed the latest strategy in searching optimal dose combination from three perspectives: (1) mainly experimental-based approach; (2) Computational-guided experimental approach; and (3) mainly computational-based approach. In addition to the introduction of each strategy, critical discussion of their advantages and disadvantages were also included, with a strong focus on the current applications and future improvements.