4-[(E)-2-(1-Pyrenyl)Vinyl]Pyridine Complexes: How to Modulate the Toxicity of Heavy Metal Ions to Target Microbial Infections.

Pyrene derivatives are regularly proposed for use in biochemistry as dyes due to their photochemical characteristics. Their antibacterial properties are, however, much less well understood. New complexes based on 4-[(E)-2-(1-pyrenyl)vinyl]pyridine (PyPe) have been synthesized with metal ions that are known to possess antimicrobial properties, such as zinc(II), cadmium(II), and mercury(II). The metal ion salts, free ligand, combinations thereof, and the coordination compounds themselves were tested for their antibacterial properties through microdilution assays. We found that the ligand is able to modulate the antibacterial properties of transition metal ions, depending on the complex stability, the distance between the ligand and the metal ions, and the metal ions themselves. The coordination by the ligand weakened the antibacterial properties of heavy metal ions (Cd(II), Hg(II), Bi(III)), allowing the bacteria to survive higher concentrations thereof. Mixing the ligand and the metal ion salts without forming the complex beforehand enhanced the antibacterial properties of the cations. Being non-cytotoxic itself, the ligand therefore balances the biological consequences of heavy metal ions between toxicity and therapeutic weapons, depending on its use as a coordinating ligand or simple adjuvant.

Co-treatment with the seed of Carthamus tinctorius L. and the aerial part of Taraxacum coreanum synergistically suppresses Aß25-35-induced neurotoxicity by altering APP processing.

Accumulation of ß-amyloid peptide (Aß) induces neurotoxicity, which is the primary risk factor in the pathogenesis of Alzheimer's disease (AD). The cleavage of amyloid precursor protein (APP) by the ß- (BACE) and γ- (PS1, PS2) secretases is a critical step in the amyloidogenic pathway. The induction of neuronal apoptosis by Aß involves increased expression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and decreased Bcl-2 expression. The seed of Carthamus tinctorius L. (CTS) and the aerial part of Taraxacum coreanum (TC) are traditional herbs used to treat several neurodegenerative diseases. In this study, the neuroprotective effects of co-treatment with CTS and TC on Aß-induced neurotoxicity in SH-SY5Y neuroblastoma cells and the underlying mechanisms were investigated. CTS, TC, and the co-treatment (CTS + TC) were added to Aß25-35-treated SH-SY5Y cells. CTS + TC synergistically increased cell viability and inhibited reactive oxygen species production. CTS + TC resulted in significant downregulation of BACE, PS1, PS2, and APP, as well as the 99-aa C-terminal domain of APP, compared with either CTS or TC alone. Compared with the single herbs, co-treatment with CTS and TC markedly decreased the expression of Bax and increased the expression of Bcl-2, consistent with its anti-apoptotic effects. These findings suggest that co-treatment with CTS and TC may be useful for AD prevention.

Ecosystem service tradeoff and synergistic relationship in the Yellow River Delta High-Efficiency Eco-Economic Zone.

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.

Ultrasonic-assisted extraction of grape seed procyanidins, preparation of liposomes, and evaluation of their antioxidant capacity.

The residue remaining after oil extraction from grape seed contain abundant procyanidins. An ultrasonic-assisted enzyme method was performed to achieve a high extraction efficiency of procyanidins when the optimal extraction conditions were 8 U/g of cellulase, ultrasound power of 200 W, ultrasonic temperature of 50 ℃, and ultrasonic reaction time of 40 min. The effects of free procyanidins on both radical scavenging activity and thermal stability at 40, 60, and 80 ℃ of the procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were discussed. The presence of procyanidins at concentrations ranging from 0.02 to 0.10 mg/mL was observed to be effective at inhibiting lipid oxidation by 15.15 % to 69.70 % in a linoleic acid model system during reaction for 168 h, as measured using the ferric thiocyanate method. The procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were characterized by measuring the mean particle size and encapsulation efficiency. Moreover, the holographic plots showed that the effect-response points of procyanidins combined with α-tocopherol in liposomes were lower than the addition line and 95 % confidence interval limits. At the same time, there were significant differences between the theoretical IC50add value and the experimental IC50mix value. The interaction index (γ) of all combinations was observed to be less than 1. These results indicated that there was a synergistic antioxidant effect between procyanidins combined with α-tocopherol, which will show promising prospects in practical applications. In addition, particle size differentiation and morphology agglomeration were observed at different time points of antioxidant activity determination (0, 48, 96 h).

Multifunctional dietary interventions, low-grade inflammation and cardiometabolic profile: a scoping review.

Background: Growing evidence highlights the significant impact of diet to modify low-grade inflammation closely linked to cardiometabolic profile. Multifunctionnal diets, combining several compounds have been shown to beneficially impact metabolic parameters. Objective: This study synthesizes the knowledge on the impact of RCTs combining dietary multifunctional compounds on low-grade inflammation in humans. We investigate whether the effects of dietary multifunctional interventions on inflammatory markers were parallel to alterations of cardiometabolic parameters. Methodology: We considered both the integrated dietary interventions (ID, i.e. global diets such as Mediterranean, Nordic…) and the dietary interventions based on selected bioactive mix (BM) compounds, in healthy individuals and those at cardiometabolic risk. Out of 221 screened publications, we selected 27 studies: 11 for BM (polyphenols and/or omega-3 fatty acids and/or antioxidants and/or dietary fiber) and 16 for ID (Mediterranean, paleo, Nordic, Dietary Approaches to Stop Hypertension (DASH) diet…). Results: ID studies reflected significant improvements in inflammatory markers (CRP, IL-6, IL-10, IL-1b), concomitantly with beneficial changes in metabolic parameters. In BM studies, pronounced effects on low-grade inflammatory markers were observed, while improvements in metabolic parameters were not consistent. Both types of studies suggested a favorable impact on oxidative stress, a factor closely linked to the inflammatory profile. Conclusion: Our findings showed that multifunctional RCT diets have differential role in managing low-grade inflammation and cardiometabolic health, with a large heterogeneity in explored inflammatory markers. Further research is imperative to elucidate the link between low-grade inflammation and other cardiometabolic risk factors, such as intestinal inflammation or postprandial inflammatory dynamics, aiming to attain a comprehensive understanding of the mechanisms involved in these processes. These future investigations not only have the potential to deepen our insights into the connections among these elements but also pave the way for significant advancements in the prevention and management of conditions related to the cardiovascular and metabolic systems.

The postbiotic sodium butyrate synergizes the antiproliferative effects of dexamethasone against the AGS gastric adenocarcinoma cells.

A growing body of literature underlines the fundamental role of gut microbiota in the occurrence, treatment, and prognosis of cancer. In particular, the activity of gut microbial metabolites (also known as postbiotics) against different cancer types has been recently reported in several studies. However, their in-depth molecular mechanisms of action and potential interactions with standard chemotherapeutic drugs remain to be fully understood. This research investigates the antiproliferative activities of postbiotics- short-chain fatty acid (SCFA) salts, specifically magnesium acetate (MgA), sodium propionate (NaP), and sodium butyrate (NaB), against the AGS gastric adenocarcinoma cells. Furthermore, the potential synergistic interactions between the most active SCFA salt-NaB and the standard drug dexamethasone (Dex) were explored using the combination index model. The molecular mechanisms of the synergy were investigated using reactive oxygen species (ROS), flow cytometry and biochemometric and liquid chromatography-mass spectrometry (LC-MS)-driven proteomics analyses. NaB exhibited the most significant inhibitory effect (p < 0.05) among the tested SCFA salts against the AGS gastric cancer cells. Additionally, Dex and NaB exhibited strong synergy at a 2:8 ratio (40 µg/mL Dex + 2,400 µg/mL NaB) with significantly greater inhibitory activity (p < 0.05) compared to the mono treatments against the AGS gastric cancer cells. MgA and NaP reduced ROS production, while NaB exhibited pro-oxidative properties. Dex displayed antioxidative effects, and the combination of Dex and NaB (2,8) demonstrated a unique pattern, potentially counteracting the pro-oxidative effects of NaB, highlighting an interaction. Dex and NaB individually and in combination (Dex:NaB 40:2400 µg/mL) induced significant changes in cell populations, suggesting a shift toward apoptosis (p < 0.0001). Analysis of dysregulated proteins in the AGS cells treated with the synergistic combination revealed notable downregulation of the oncogene TNS4, suggesting a potential mechanism for the observed antiproliferative effects. These findings propose the potential implementation of NaB as an adjuvant therapy with Dex. Further investigations into additional combination therapies, in-depth studies of the molecular mechanisms, and in vivo research will provide deeper insights into the use of these postbiotics in cancer, particularly in gastric malignancies.

High-dose ascorbate exerts anti-tumor activities and improves inhibitory effect of carboplatin through the pro-oxidant function pathway in uterine serous carcinoma cell lines.

OBJECTIVE: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. METHODS: Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. RESULTS: High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. CONCLUSIONS: Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.

Discovery of Gambogic acid as an antibacterial adjuvant against vancomycin-resistant enterococci in vitro and in vivo.

BACKGROUND: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity. PURPOSE: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin. METHODS: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determination, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored. RESULTS: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 µg/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity. CONCLUSIONS: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo. These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.

The Antimicrobial Potential of the Hop (Humulus lupulus L.) Extract against Staphylococcus aureus and Oral Streptococci.

Plant extracts are in the focus of the pharmaceutical industry as potential antimicrobials for oral care due to their high antimicrobial activity coupled with low production costs and safety for eukaryotic cells. Here, we show that the extract from Hop (Humulus lupulus L.) exhibits antimicrobial activity against Staphylococcus aureus and Streptococci in both planktonic and biofilm-embedded forms. An extract was prepared by acetone extraction from hop infructescences, followed by purification and solubilization of the remaining fraction in ethanol. The effect of the extract on S. aureus (MSSA and MRSA) was comparable with the reference antibiotics (amikacin, ciprofloxacin, and ceftriaxone) and did not depend on the bacterial resistance to methicillin. The extract also demonstrated synergy with amikacin on six S. aureus clinical isolates, on four of six isolates with ciprofloxacin, and on three of six isolates with ceftriaxone. On various Streptococci, while demonstrating lower antimicrobial activity, an extract exhibited a considerable synergistic effect in combination with two of three of these antibiotics, decreasing their MIC up to 512-fold. Moreover, the extract was able to penetrate S. aureus and S. mutans biofilms, leading to almost complete bacterial death within them. The thin-layer chromatography and LC-MS of the extract revealed the presence of prenylated flavonoids (2',4',6',4-tetrahydroxy-3'-geranylchalcone) and acylphloroglucides (cohumulone, colupulone, humulone, and lupulone), apparently responsible for the observed antimicrobial activity and ability to increase the efficiency of antibiotics. Taken together, these data suggest an extract from H. lupulus as a promising antimicrobial agent for use both as a solely antiseptic and to potentiate conventional antimicrobials.

Multi-ecosystem services differently affected by over-canopy and understory nitrogen additions in a typical subtropical forest.

Obtaining a holistic understanding of the impacts of atmospheric nitrogen deposition on multiple ecosystem services of forest is essential for developing comprehensive and sustainable strategies, particularly in heavy N deposition regions such as subtropical China. However, such impacts remain incompletely understood, with most previous studies focus on individual ecosystem function or service via understory N addition experiments. To address this knowledge gap, we quantified the effects of over-canopy and understory N additions on multiple ecosystem services based on a 7-year large-scale field experiment in a typical subtropical forest. Our results showed continued over-canopy N addition with 50 kg ha-1 year-1 over a period of 4-7 years significantly increased plant nutrient retention, but did not affect the services of soil nutrient accumulation, water yield, C sequestration (in plants and soil), or oxygen release. There were trade-offs between the soil and plant on providing the services of nutrient accumulation/retention and C sequestration under over-canopy N addition. However, without uptake and retention of tree canopy, the trade-off between soil and plant were more weaken under the understory N addition with 50 kg ha-1 year-1 , and their relationships were even synergetic under the understory N addition with 25 kg ha-1 year-1 . The results suggest that understory N addition cannot accurately simulate the effects of atmospheric N deposition on multiple services, along with mutual relationships. Interestingly, the services of plant N, P retention, and C sequestration exhibited a synergetic increase under the over-canopy N addition but a decrease under the understory N addition. Our results also found tree layer plays a primary role in providing plant nutrient retention service and is sensitive to atmospheric N deposition. Further studies are needed to investigate the generalized effects of forest canopy processes on alleviating the threaten of global change factors in different forest ecosystems.

Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model.

IMPORTANCE: Multidrug resistance is a rising problem among non-Candida albicans species, such as Candida auris. This therapeutic problem has been very important during the COVID-19 pandemic. The World Health Organization has included C. auris in its global priority list of health-threatening fungi, to study this emerging multidrug-resistant species and to develop effective alternative therapies. In the present study, the synergistic effect of the combination of amphotericin B and echinocandins has been demonstrated against blood isolates of C. auris. Different susceptibility responses were also observed between aggregative and non-aggregative phenotypes. The antifungal activity of these drug combinations against C. auris was also demonstrated in the Caenorhabditis elegans host model of candidiasis, confirming the suitability and usefulness of this model in the search for solutions to antimicrobial resistance.

Synergistic improvements in energy recovery and bio-oil quality through integrated thermochemical valorization of agro-industrial waste of varying moisture content.

Two thermochemical valorization schemes were investigated for co-upgrading dry and wet agricultural wastes through integrated hydrothermal carbonization (HTC) and pyrolysis. In the first pathway, dry and wet wastes were co-carbonized. The resulting hydrochar was pyrolyzed to yield an energy dense biochar (26-32 MJ/kg) high in fixed carbon (41-86 wt%) and low in volatile matter (6-12 wt%). The resulting bio-oil was lower in carboxylic acids and higher in phenols than predicted based on an additive scheme. In pathway two, wet waste (only) underwent HTC and the resulting hydrochar was mixed with dry waste and the mixture pyrolyzed. This pathway showed a lower biochar yield (32-67 wt%) and lower HHV values (24-31 MJ/kg) but higher fixed carbon content (65-84 wt%). The bio-oil contained more carboxylic acids than pathway 1 bio-oil. Pathway 1 biochars were more thermally reactive than pathway 2 biochars, reflecting a synergistic deoxygenation that occurs when incorporating dry waste in HTC prior to pyrolysis.

A novel off-line multi-dimensional high-speed countercurrent chromatography strategy for preparative separation of bioactive neolignan isomers from Piper betle. L.

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate-methanol-water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1'S)-1'-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1-6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products.

Bioremediation of hydrocarbon by co-culturing of biosurfactant-producing bacteria in microbial fuel cell with Fe2O3-modified anode.

The most common type of environmental contamination is petroleum hydrocarbons. Sustainable and environmentally friendly treatment strategies must be explored in light of the increasing challenges of toxic and critical wastewater contamination. This paper deals with the bacteria-producing biosurfactant and their employment in the bioremediation of hydrocarbon-containing waste through a microbial fuel cell (MFC) with Pseudomonas aeruginosa (exoelectrogen) as co-culture for simultaneous power generation. Staphylococcus aureus is isolated from hydrocarbon-contaminated soil and is effective in hydrocarbon degradation by utilizing hydrocarbon (engine oil) as the only carbon source. The biosurfactant was purified using silica-gel column chromatography and characterised through FTIR and GCMS, which showed its glycolipid nature. The isolated strains are later employed in the MFCs for the degradation of the hydrocarbon and power production simultaneously which has shown a power density of 6.4 W/m3 with a 93% engine oil degradation rate. A biogenic Fe2O3 nanoparticle (NP) was synthesized using Bambusa arundinacea shoot extract for anode modification. It increased the power output by 37% and gave the power density of 10.2 W/m3. Thus, simultaneous hydrocarbon bioremediation from oil-contamination and energy recovery can be achieved effectively in MFC with modified anode.

An Insight into Emerging Phytocompounds for Glioblastoma Multiforme Therapy.

Despite intense research in the field of glioblastoma multiforme (GBM) therapeutics, the resistance against approved therapy remains an issue of concern. The resistance against the therapy is widely reported due to factors like clonal selection, involvement of multiple developmental pathways, and majorly defective mismatch repair (MMR) mediated by O6- methylguanine DNA methyltransferase (MGMT). Phytotherapy is one of the most effective alternatives to overcome resistance. It involves plant-based compounds, divided into several classes: alkaloids; phenols; terpenes; organosulfur compounds. The phytocompounds comprised in these classes are extracted or processed from certain plant sources. They can target various proteins of molecular pathways associated with the progression and survival of GBM. Phytocompounds have also shown promise as immunomodulatory agents and are being explored for immune checkpoint inhibition. Therefore, research and innovations are required to understand the mechanism of action of such phytocompounds against GBM to develop efficacious treatments for the same. This review gives insight into the potential of phytochemical-based therapeutic options for GBM treatment.

Nutrient synergy: definition, evidence, and future directions.

Nutrient synergy refers to the concept that the combined effects of two or more nutrients working together have a greater physiological impact on the body than when each nutrient is consumed individually. While nutrition science traditionally focuses on isolating single nutrients to study their effects, it is recognized that nutrients interact in complex ways, and their combined consumption can lead to additive effects. Additionally, the Dietary Reference Intakes (DRIs) provide guidelines to prevent nutrient deficiencies and excessive intake but are not designed to assess the potential synergistic effects of consuming nutrients together. Even the term synergy is often applied in different manners depending on the scientific discipline. Considering these issues, the aim of this narrative review is to investigate the potential health benefits of consuming different nutrients and nutrient supplements in combination, a concept we define as nutrient synergy, which has gained considerable attention for its impact on overall well-being. We will examine how nutrient synergy affects major bodily systems, influencing systemic health. Additionally, we will address the challenges associated with promoting and conducting research on this topic, while proposing potential solutions to enhance the quality and quantity of scientific literature on nutrient synergy.

Three alginate lyases provide a new gut Bacteroides ovatus isolate with the ability to grow on alginate.

Humans consume alginate in the form of seaweed, food hydrocolloids, and encapsulations, making the digestion of this mannuronic acid (M) and guluronic acid (G) polymer of key interest for human health. To increase knowledge on alginate degradation in the gut, a gene catalog from human feces was mined for potential alginate lyases (ALs). The predicted ALs were present in nine species of the Bacteroidetes phylum, of which two required supplementation of an endo-acting AL, expected to mimic cross-feeding in the gut. However, only a new isolate grew on alginate. Whole-genome sequencing of this alginate-utilizing isolate suggested that it is a new Bacteroides ovatus strain harboring a polysaccharide utilization locus (PUL) containing three ALs of families: PL6, PL17, and PL38. The BoPL6 degraded polyG to oligosaccharides of DP 1-3, and BoPL17 released 4,5-unsaturated monouronate from polyM. BoPL38 degraded both alginates, polyM, polyG, and polyMG, in endo-mode; hence, it was assumed to deliver oligosaccharide substrates for BoPL6 and BoPL17, corresponding well with synergistic action on alginate. BoPL17 and BoPL38 crystal structures, determined at 1.61 and 2.11 Å, respectively, showed (α/α)6-barrel + anti-parallel ß-sheet and (α/α)7-barrel folds, distinctive for these PL families. BoPL17 had a more open active site than the two homologous structures. BoPL38 was very similar to the structure of an uncharacterized PL38, albeit with a different triad of residues possibly interacting with substrate in the presumed active site tunnel. Altogether, the study provides unique functional and structural insights into alginate-degrading lyases of a PUL in a human gut bacterium.IMPORTANCEHuman ingestion of sustainable biopolymers calls for insight into their utilization in our gut. Seaweed is one such resource with alginate, a major cell wall component, used as a food hydrocolloid and for encapsulation of pharmaceuticals and probiotics. Knowledge is sparse on the molecular basis for alginate utilization in the gut. We identified a new Bacteroides ovatus strain from human feces that grew on alginate and encoded three alginate lyases in a gene cluster. BoPL6 and BoPL17 show complementary specificity toward guluronate (G) and mannuronate (M) residues, releasing unsaturated oligosaccharides and monouronic acids. BoPL38 produces oligosaccharides degraded by BoPL6 and BoPL17 from both alginates, G-, M-, and MG-substrates. Enzymatic and structural characterization discloses the mode of action and synergistic degradation of alginate by these alginate lyases. Other bacteria were cross-feeding on alginate oligosaccharides produced by an endo-acting alginate lyase. Hence, there is an interdependent community in our guts that can utilize alginate.

Synergistic combination of Cinnamomum verum and Syzygium aromaticum treatment for cutaneous leishmaniasis and investigation of their molecular mechanism of action.

Combination therapy at appropriately suitable doses presents a promising alternative to monotherapeutic drugs. In this study, Cinnamomum verum and Syzygium aromaticum essential oils and their major compounds have exhibited substantial leishmaniacidal potential against both promastigote and amastigote forms of Leishmania (L.) major. However, they displayed high cytotoxicity against Raw264.7 macrophage cells. Interestingly, when combined with each other or with amphotericin B, they demonstrated a synergistic effect (FIC<0.5) with low cytotoxicity. These combinations are able to modulate the production of nitric oxide (NO) by macrophages. Notably, the combination of S. aromaticum Essential oil with amphotericin B stimulates macrophage cells by increasing NO production to eliminate leishmanial parasites. Furthermore, investigation of the molecular mechanism of action of these synergistic combinations reveals potent inhibition of the sterol pathway through the inhibition of the CYP51 gene expression. The findings suggest that combination therapy may offer significant therapeutic benefits in both food and pharmaceutical fields.

Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system.

Cancer is a malignant disease that has plagued human beings all the time, but the treatment effect of commonly used anticancer drugs in clinical practice is not ideal by reason of their drug tolerance and Strong adverse reactions to patients. Therefore, it is imperative to find effective and low-toxic anticancer drugs. Many research works have shown that natural products in Chinese herbal medicine have great anticancer potential, such as 6-shogaol, a monomer composition obtained from Chinese herbal ginger, which has been confirmed by numerous in vitro or vivo studies to be an excellent anti-cancer active substance. In addition, most notably, 6-shogaol has different selectivity for normal and cancer cells during treatment, which makes it valuable for further research and clinical development. Therefore, this review focus on the anti-cancer attributes, the mechanism and the regulation of related signaling pathways of 6-shogaol. In addition, its synergy with commonly used anticancer drugs, potential drug delivery systems and prospects for future research are discussed. This is the first review to comprehensively summarize the anti-cancer mechanism of 6-shogaol, hoping to provide a theoretical basis and guiding significance for future anti-cancer research and clinical development of 6-shogaol.

Advanced treatment and Resource recovery of brewery wastewater by Co-cultivation of filamentous microalga Tribonema aequale and autochthonous Bacteria.

To use unicellular microalgae to remove waste nutrients from brewery wastewater while converting them into algal biomass has been explored but high-cost treatment and low-value biomass associated with current technologies have prevented this concept from further attempts. In this study, a filamentous microalga Tribonema aequale was introduced and the alga can grow vigorously in brewery wastewater and algal biomass concentration could be as high as 6.45 g L-1 which can be harvested by a cost-effective filtration method. The alga together with autochthonous bacteria removed majority of waste nutrients from brewery wastewater. Specifically, 85.39% total organic carbon (TOC), 79.53% total dissolved nitrogen (TN), 93.38% ammonia nitrogen (NH3-N) and 71.33% total dissolved phosphorus (TP) in brewery wastewater were rapidly removed by co-cultivation of T. aequale and autochthonous bacteria. Treated wastewater met the national wastewater discharge quality, and resulting algal biomass contained large amounts of high-value products chrysolaminarin, palmitoleic acid (PLA) and eicosapentaenoic acid (EPA). It is anticipated that reduced cost of algal harvesting coupled with value-added biomass could make T. aequale as a promising candidate for brewery wastewater treatment and resource utilization.