Concentration-dependent Way Research Articles

Inhibition of Candida albicans virulence by moscatin from Dendrobium nobile lindl.

Candida albicans infection poses a significant global health threat. It is imperative to exploit new antifungal agents against C. albicans infections without leading to drug resistance, so that these potential agents can complement or combine with current medications to effectively treat diseases caused by C. albicans. We screened moscatin, and assessed the inhibitory effectiveness against C. albicans SC5314 on hyphae production and biofilm formation. It was revealed that moscatin exhibited significant effects on morphological transition and biofilm formation in C. albicans SC5314. It also lowered the pathogenicity of C. albicans SC5314 in a concentration-dependent way in both A549 cells and mice fungal infection models, but had no cytotoxicity to A549 cells. In addition, moscatin attenuated the virulence of clinical fluconazole-resistant C. albicans and exhibited synergistic activity with fluconazole. It could also restore the composition and richness of the intestinal microbiota in mice infected by C. albicans. These findings indicate that these moscatin has great potential to be developed as a new therapeutic drug against C. albicans infection.

Quercetin has a protective impact on human umbilical vein endothelial cells against tungsten carbide cobalt nanoparticle-induced cytotoxicity, oxidative stress, apoptosis

Oxidative stress is a pivotal factor in the pathogenesis of various cancer diseases. In fact, oxidative DNA damage is described as the type of damage probably to occur in cancer cells. This study examined the protective impact of the polyphenolic compound quercetin on human umbilical vein endothelial (HUVEC) cells against tungsten carbide cobalt nanoparticles (WC-Co NPs)-induced oxidative stress, cytotoxicity, and apoptosis. One of the most often used models for studying endothelial cells in vitro is the human umbilical vein epithelial cell. Scanning electron microscope (SEM) and transmission electron microscopy (TEM) were used to measure the size of the NPs prior to WC-Co NPs treatment. WC-Co NPs had a polygonal form and measured 45.26 ± 1 nm in size. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),neutral red uptake(NRU) and lactate dehydrogenase (LDH) assays, the cytotoxicity of WC-Co NPs on HUVECs cells was assessed. The cytotoxicity of NPs increased in a concentration-dependent way. The MTT result was used to calculate the median inhibitory concentration (IC50) for HUVEC cells at 24 h, which came out to be 23.14 μg/ml. Intracellular reactive oxygen species(ROS) and lipid peroxidation(LPO) levels were elevated at 17 g/ml WC-Co NPs and then reduced in HUVECs cells upon immediate exposure to 150 µM quercetin (QR). Using JC-1 staining, the loss of mitochondrial membrane potential(MMP) in control, WC-Co NPs alone and WC-Co NPs plus QR exposed cell were evaluated. In HUVECs cells, maximum apoptotic cells were seen at increasing NPs concentrations. Based on the impacts of NPs on HUVECs cells, the data suggests that QR may work on the process of scavenging ROS, which is responsible for DNA repair. Consequently, the above findings highlight the significance of these QR as defenses against DNA damage brought on by oxidative stress, which frequently happens in a number of cancer disorders.

Ethanolic Extract of Salvia officinalis Leaves Affects Viability, Survival, Migration, and the Formation and Growth of 3D Cultures of the Tumourigenic Murine HPV-16+-Related Cancer Cell Line.

Salvia officinalis (SO) is one of the most widely used plants in traditional medicine worldwide. In the present study, the effect of an ethanolic extract of S. officinalis leaves on hallmarks of cancer of HPV-16-positive cancer tumorigenic cells, TC-1, was analyzed in vitro. Phytochemical and spectroscopic analysis were performed. Additionally, the extract's flavonoid content, reducing iron, and antioxidant capacity were determined. In regard to the in vitro tests, the cytotoxic activity and its effect on the replicative capacity and on the cell migration of TC-1 cells were analyzed by viability and clonogenic, survival, and wound healing assays. The effect of a pre-treatment or treatment on 3D culture formation, growth, and reversion capacity was also examined. The results of the phytochemical analysis allowed the detection of tannins, saponins, steroids, and flavonoids. The flavonoids content was found to be 153.40 ± 10.68 µg/mg of extract. Additionally, the extract exhibited an antioxidant capacity and a ferric-reducing capacity of around 40% compared to the ascorbic acid. Thin layer chromatographic (TLC) analysis and spectroscopic tests showed the presence of compounds similar to quercetin and catechin flavonoids in the extract. In the in vitro assays, the SO extract induced in a concentration-dependent way changes in cell morphology, the decrease of cell viability, survival, and migration. At a concentration of 125 µg/mL, the extract inhibited spheroid formation, reduced their growth, and affected their reversion to 2D. Ethanolic extract of S. officinalis leaves had inhibitory effects on hallmarks of the cancer line HPV-16+. This suggests that the phytochemicals present in it may be a source of chemotherapeutics against cervical cancer.

Curcumin Inhibits the Development of Pancreatic Cancer by Targeting the circ_0079440/miR-522-3p/EIF4A1 Pathway.

Pancreatic cancer (PC) is a common gastrointestinal cancer with high invasiveness and high mortality. Curcumin is a natural polyphenol with anti-tumor activity against different cancers, including PC. Curcumin has been verified to mediate the expression of circular RNAs (circRNAs) to inhibit tumor development. This study aimed to explore the function and regulatory mechanism of curcumin on circ_0079440 in PC. PC cells were treated with different concentrations of curcumin (0, 5, 10 or 15 μM) for 24 h. Gene expression in PC cells and tissues was detected using RT-qPCR. Cell malignant phenotypes were determined by functional assays. The levels of EMT-related proteins were tested using western blot. RNA interaction was determined using RNA pulldown assay, luciferase reporter assay and RIP assay. The results showed that curcumin suppressed cell proliferative, migratory, and invasive capabilities, and weakened epithelial-mesenchymal transition (EMT) in a concentration-dependent way. Circ_0079440 was expressed at a high level in PC and its level was reduced via curcumin administration in PC cells. Rescue assays showed that circ_0079440 overexpression reversed the suppressive effects of curcumin on PC cell malignant phenotypes. Furthermore, in the xenograft mouse models, curcumin treatment inhibited tumor growth and metastasis, and circ_0079440 upregulation reversed the function of curcumin. Additionally, circ_0079440 was revealed to bind to miR-522-3p to upregulate eukaryotic initiation factor 4A1 (EIF4A1) expression in PC cells. EIF4A1 expression was also downregulated by curcumin, and EIF4A1 overexpression abolished the suppressive functions of curcumin. Moreover, EIF4A overexpression or miR-522-3p inhibition counteracted the anti-tumor effects of circ_0079440 depletion on PC development. To sum up, curcumin suppresses PC development by targeting the circ_0079440/miR-522-3p/EIF4A1 pathway, which might provide novel therapeutic targets for treatment of PC.

Cinnamaldehyde potentiates cytotoxic and apoptogenic effects of doxorubicin in prostate cancer cell line.

Nowadays, herbal medicine has been utilized to treat various diseases such as cancer, which showed successful therapeutic efficacy in previous studies. This study for the first time evaluated the cytotoxic potential of cinnamaldehyde (CIN) alone and in combination with doxorubicin (DOX), a well-known potent anti-tumor agent, on the proliferation of prostatic cancer cell line (PC3). The cytotoxicity and apoptotic activities of CIN and DOX, either separately or together, were determined on PC3 cells by the MTT test and Annexin V/PI assay, respectively. To further investigate which apoptotic pathway participated in cell death a collection of prominent markers of apoptosis induction including caspase-3/7 activations, mitochondrial membrane potential (MMP), and phosphatidyl serine translocation were detected. The different concentrations of CIN and DOX significantly inhibited the proliferation of PC3 cells in a concentration-dependent way within a 24-h treatment. In addition, the induction of apoptosis by CIN was accompanied by an increase in the activation of caspase-3/7 in PC3 cells with IC50 concentrations of 12.5 and 10 μg/mL for CIN and DOX, respectively. Moreover, the morphological observations obtained from flow cytometry MMP and caspase-3/7 activity assays, altogether, revealed the potential effect of CIN on apoptosis induced in PC3 cells by DOX. Taken together, the current study concluded that the combination of CIN and DOX could lead to the production of a potential therapeutic agent for prostate cancer. However, further in vivo and clinical studies are still needed to validate this combination in prostate cancer therapy.

A Promising Therapeutic Scaffold Fusing Chalcone/Coumarin Targeting Colorectal Cancer: Design, Synthesis, Biological and ADME‐tox Modelling

AbstractEight novel compounds incorporating chalcone and coumarin features, namely chalcone‐coumarin‐ hybrid molecules, were designed, synthetized, and evaluated for their activity against human colorectal carcinoma SW480 cell line. According to the results observed, the hybrid with a 2,3‐dimetoxysubstitution pattern displayed the highest activity at the conditions evaluated, with an IC50 value of 25.18±1.12 μM, being even more active than the reference drug (5‐fluorouracil) and the parental compound (7‐methylcoumarin). In addition, this hybrid compound exhibited significant antiproliferative activity in a time‐ and concentration dependent way, suggesting rather a cytostatic or cytotoxic effect. Moreover, a theoretical drug‐like/pharmacokinetics/toxicological study suggested that the most promising hybrid would have a great chance to advance to further preclinical studies as anti‐cancer therapeutic candidate for oral oncological management. Our study evidently identified the potency of chalcone‐coumarin conjugates, particularly the 2,3‐dimetoxysubstituited molecule to be a prototype drug for further investigations toward novel therapeutics treatments of colorectal cancer.

Molecular Interactions Between Egg White Peptides and Giant Unilamellar Vesicle Membranes: Effect of Peptide Localization on Membrane Fluidity.

Bioactive peptides have been shown to affect cell membrane fluidity, which is an important indicator of the cell membrane structure and function. However, the underlying mechanism of egg white-derived bioactive peptide regulation of cell membrane fluidity has not been elucidated yet. The cell membrane fluidity was investigated by giant unilamellar vesicles in the present study. The results showed that peptides TCNW, ADWAK, ESIINF, VPIEGII, LVEEY, and WKLC connect to membranes through intermolecular interactions, such as hydrogen bonding and regulated membrane fluidity, in a concentration-dependent way. In addition, peptides prefer to localize in the hydrophobic core of the bilayers. This study provides a theoretical basis for analyzing the localization of egg white bioactive peptides in specific cell membrane regions and their influence on the cell membrane fluidity.

Fraxetin pretreatment alleviates cisplatin-induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation.

Cisplatin-induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti-inflammatory, and anti-fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin-induced kidney injury in a time- and concentration-dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin-induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin-treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT-repeats binding site on mTORC1 protein. In summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

Toxicological insight of magnetite nanogel: neuro-ethological, hepato-renal, antioxidant, and histopathological traits in Clarias gariepinus

Assessment of acute toxicity of magnetic nanogel (MNG) is crucial to conclude the safe applicable dose and to warrant its application in aquaculture. Therefore, the current study is a novel step to assess behavior, neuro-stress response, hepato-renal, oxidative, and histopathological variations produced by MNG’ acute toxicity in Clarias gariepinus. Two experiments were conducted: the first was a determination of the 96-h lethal concentration 50 (LC50) of MNG in C. gariepinus. Meanwhile, the second was an assessment of the toxicological impacts of three different concentrations of MNG in C. gariepinus following a 10-day exposure period and a subsequent 10-day depuration trial. One hundred and eighty fish were allotted to four groups exposed to 0, 1/10, 1/8, or 1/5 96-h LC50 of MNG. The outcomes exhibited that 96-h LC50 of MNG for C. gariepinus was 44 mg/L. The subjected group to MNG induced a concentration-dependent elevation in the serum values of cortisol, alanine transaminase, aspartate transaminase, urea, and creatinine following MNG exposure. Marked elevation in the oxidative stress indicators (catalase (CAT), glutathione S-transferase activity (GST), and superoxide dismutase (SOD)) was also evident. Meanwhile, the value of the neurological biomarker, acetylcholinesterase (AChE), was markedly reduced in a concentration-dependent way. These biochemical changes were complemented by pathological alterations in the hepato-renal architecture. Interestingly, in response to the 10-day depuration period, most of the tested parameters were eliminated in C. gariepinus exposed to 1/10 of LC50. Conclusively, MNG can induce numerous adverse effects only at higher doses (1/5 and 1/8 of LC50). Meanwhile, the lowest tested concentration of MNG (1/10 of LC50) was safe for application in aquaculture practices with only mild disruptions in the bio-indices. In addition, a retrieval period of 10 days was sufficient to renovate these alterations only in fish exposed to the same concentration.

Anticancer Action of Silver Nanoparticles in SKBR3 Breast Cancer Cells through Promotion of Oxidative Stress and Apoptosis.

Silver nanoparticles (AgNPs) are known as one of the highly utilized NPs owing to their unique characteristics in the field of cancer research. The goal of this research was to explore the oxidative stress, apoptosis, and angiogenesis in SKBR3 breast cancer cells after exposure to AgNPs. The survival rate of SKBR3 cancer cells and MCF-10A normal breast cells was assessed under the effects of different concentrations (0, 32, 64, 128, and 250 μg/ml) by MTT method. The oxidative condition was assessed by measuring reactive oxygen species (ROS) production, total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), and antioxidant enzyme activity (CAT, GPx, and CAT) using colorimetric-based kits. Flow cytometry and Hoechst 33258 staining were performed to investigate the induction of apoptosis. Furthermore, the expression of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and caspase 3 and 7 activity was measured. The cell migration and vascular endothelial growth factor-A (VEGF-A) gene expression, protein kinase B (AKT), phosphatidylinositol 3-kinase (PI3K) were also studied. The MTT results indicated that AgNPs inhibit the SKBR3 cells' viability in a concentration-dependent way. Besides, AgNPs markedly induced oxidative stress via increasing TOS content, MDA production, reduction of TAC, and regulation of antioxidant enzyme level. Additionally, AgNPs promoted apoptosis as revealed by an enhancement in Bax/Bcl-2 expression ratio. Findings also indicated that AgNPs suppress the expression of genes (VEGF-A, AKT, and PI3K) involved in angiogenesis. Altogether, our data revealed that AgNPs initiate oxidative stress and apoptosis in SKBR3 breast cancer cells, dose dependently.

Fast multispectral imaging analysis as phenotyping platform: Effect of titanium dioxide nanoparticles on microalgae physiology

Several types of nanoparticles have been developed and explored in agricultural applications and their environmental impact evaluated. However, no such study was carried out using fully dispersible ultrasmall titanium dioxide nanoparticles (us-TiO2). Therefore, we investigate the effects of fully dispersible 2.5 nm large us-TiO2 nanoparticles on the cellular metabolism of the microalgae Chlamydomonas reinhardtii using multispectral imaging analysis as a platform for the evaluation of their physiological responses. Our results indicate that us-TiO2 modulates the microalgae cell growth in a concentration-dependent manner. X-ray fluorescence analysis showed that the us-TiO2 strongly interacts with the cells in relatively low and constant amounts in the range of 0.05 g·L−1 to 1.5 g·L−1. Most nanoparticles were found on the cell surface, surrounding the microalgae cells dispersed in TAP medium, indicating a low trend of internalization. We further applied multispectral imaging analyses toward fast phenotyping of the alterations in the cell's physiology. Furthermore, higher concentrations of us-TiO2 (~1 g·L−1) positively affect the microalgae photosynthetic activity and growth. Thus, our results indicated the capacity to detect variations in cell physiology and indicated a possible role of us-TiO2 in modulating positively microalgae photosynthesis and growth in a concentration-dependent way. The mechanisms controlling such responses must be further investigated.

Suppressing Endoplasmic Reticulum Stress Alleviates LPS-Induced Acute Lung Injury via Inhibiting Inflammation and Ferroptosis.

Acute lung injury (ALI) is a life-threatening clinical disorder with high mortality rate. Ferroptosis is a new type of programmed cell death with lipid peroxidation and iron ion overloading as the main characteristics. Endoplasmic reticulum (ER) stress and ferroptosis play pivotal roles in the pathogenesis of ALI. The study aimed to investigate the underlying relationship between ER stress and ferroptosis in ALI. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated LPS-induced inflammation, and decreased IL-1β, IL-6, and TNF-α levels in BALF and lungs. The increased MDA and decreased GSH induced by LPS were partially reversed by 4-PBA, which also inhibited the expressions of ferroptosis-related protein ACSL4, COX-2, and FTH1. TEM further confirmed the ferroptosis within airway epithelia cells was ameliorated by 4-PBA. Moreover, 4-PBA reduced the production of ROS and lipid ROS in LPS-exposed BEAS-2B cells in a concentration-dependent way. Meanwhile, 4-PBA mitigated LPS-induced cell apoptosis in vivo and in vitro. Mechanistically, the MAPK signaling pathway activated by LPS was downregulated by 4-PBA. Collectively, these findings suggested that 4-PBA protected against ALI by inhibiting inflammation and ferroptosis through downregulating ER stress, thus providing a potential intervention for ALI and revealing the possible interaction between ER stress and ferroptosis in ALI.

Assessing viral freshwater hazard using a toxicokinetic model and Dreissena polymorpha

The detection all pathogenic enteric viruses in water is expensive, time-consuming, and limited by numerous technical difficulties. Consequently, using reliable indicators such as F-specific RNA phages (FRNAPH) can be well adapted to assess the risk of viral contamination of fecal origin in surface waters. However, the variability of results inherent to the water matrix makes it difficult to use them routinely and to interpret viral risk. Spatial and temporal variability of surface waters can lead to underestimate this risk, in particular in the case of low loading. The use of bivalve mollusks as accumulating systems appears as a promising alternative, as recently highlighted with the freshwater mussel Dreissena polymorpha, but its capacity to accumulate and depurate FRNAPH needs to be better understood and described. The purpose of this study is to characterise the kinetics of accumulation and elimination of infectious FRNAPH by D. polymorpha in laboratory conditions, formalised by a toxico-kinetic (TK) mechanistic model. Accumulation and depuration experiments were performed at a laboratory scale to determine the relationship between the concentration of infectious FRNAPH in water and the concentration accumulated by D. polymorpha. The mussels accumulated infectious FRNAPH (3–5.4 × 104 PFU/g) in a fast and concentration-dependent way in only 48 h, as already recently demonstrated. The second exposure demonstrated that the kinetics of infectious FRNAPH depuration by D. polymorpha was independent to the exposure dose, with a T90 (time required to depurate 90 % of the accumulated concentration) of approximately 6 days. These results highlight the capacities of D. polymorpha to detect and reflect the viral pollution in an integrative way and over time, which is not possible with point water sampling. Different TK models were fitted based on the concentrations measured in the digestive tissues (DT) of D. polymorpha. The model has been developed to formalise the kinetics of phage accumulation in mussels tissues through the simultaneous estimation of accumulation and depuration rates. This model showed that accumulation depended on the exposure concentration, while depuration did not. Standardized D. polymorpha could be easily transplanted to the environment to predict viral concentrations using the TK model defined in the present study to predict the level of contamination of bodies of water on the basis of the level of phages accumulated by the organisms. It will be also provide a better understanding of the dynamics of the virus in continental waters at different time and spatial scales, and thereby contribute to the protection of freshwater resources.

Baicalin Promotes Apoptosis of Human Medullary Breast Cancer via the ERK/p38 MAPK Pathway

Objectives The present study aims to examine the effects of baicalin on the human medullary breast carcinoma (MBC) cell line Bcap-37 and to determine whether baicalin regulates Bcap-37 cell apoptosis through the ERK/p38 mitogen-activated protein kinase (MAPK) signaling pathway. Materials and Methods 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Transwell assay were utilized to measure the effects of baicalin on the proliferation and migration ability of Bcap-37 cells, respectively. Flow cytometer analysis was implied to detect the effects of baicalin on Bcap-37 cell apoptosis. Real-time quantitative polymerase chain reaction (RT-PCR) was conducted to observe the influence of baicalin on mRNA expressions of apoptosis-related genes. Western blot was executed to further explore the action of baicalin on apoptosis-related proteins. PD98059 (a specific inhibitor of ERK) and SB203580 (a specific inhibitor of p38 MAPK) were used to further clarify the intrinsic mechanism of baicalin regulating apoptosis in Bcap-37 cells. Results Compared with the control group, baicalin significantly inhibits the proliferation activity of Bcap-37 cells in a concentration- and time-dependent manner, with a p-value < 0.05. The transwell assay indicated that the migration viability of cells decreased further, followed by the increased concentration of baicalin, and the p-value had a statistical difference. Besides, flow cytometry was conducted to assess the effects of baicalin on the early and late apoptosis rates of Bcap-37 cells, and results showed that baicalin highly promoted the apoptosis level both at the early and late stages with a statistical difference in a concentration-dependent manner ( p < 0.05). Results of RT-PCR presented that, compared with the control group, baicalin significantly activated the mRNA expression of Bax, p38, and p-ERK1 and abolished the mRNA expression of Bcl-2 in every dosing group in a concentration-dependent way ( p < 0.05). Western blot exhibited that, compared with the control group, baicalin promoted the protein expression of caspase-3, caspase-9, Bax, p38, P-ERK, and p53 while playing an opposite function to Bcl-2 in each dosing group ( p values have statistical differences). At last, PD98059 and SB203580 were applied to explore the potential mechanism of baicalin in apoptosis promotion. And results revealed that, compared with the group treated with baicalin alone, protein expression of Bax, p38, p-ERK, caspase-3, and caspase-9 was downregulated obviously in the group treated with both baicalin and PD98059 or SB203580 ( p < 0.05). The p53 expression inhibition showed a difference only when compared to the group adding PD98059. Compared with the blank group, a statistical difference was only observed in Bcl-2 expression in the group treated with baicalin in combination with PD98059 or SB203580 ( p < 0.05). Interestingly, a p53 expression difference was only displayed between the blank group and the group treated with baicalin and SB203580 ( p < 0.05). Conclusion Our study observed that baicalin inhibits the proliferation and migration ability of Bcap-37 cells. In addition, baicalin induces cell apoptosis via the ERK/p38 MAPK signal pathway.

Footprint analysis of CO2 in microbial community succession of raw milk and assessment of its quality.

With the growing production of raw milk, interest has been increasing in its quality control. CO2, as a cold processing additive, has been studied to extend the cold storage period and improve the quality of raw milk. However, it is yet uncertain how representative microbial species and biomarkers can succeed one another at distinct critical periods during refrigeration. Therefore, the effects of CO2 treatment on the succession footprint of the microbial community and changes in quality during the period of raw milk chilling were examined by 16S rRNA analysis combined with electronic nose, and electronic tongue techniques. The results indicated that, the refrigeration time was shown to be prolonged by CO2 in a concentration-dependent way. And CO2 treatment was linked to substantial variations in beta and alpha diversity as well as the relative abundances of various microbial taxa (p < 0.01). The dominant bacterial phylum Proteobacteria was replaced with Firmicutes, while the major bacterial genera Acinetobacter and Pseudomonas were replaced with lactic acid bacteria (LAB), including Leuconostoc, Lactococcus, and Lactobacillus. From the perspective of biomarkers enriched in CO2-treated sample, almost all of them belong to LAB, no introduction of harmful toxins has been found. The assessment of the quality of raw milk revealed that CO2 improved the quality of raw milk by lowering the acidity and the rate of protein and fat breakdown, and improved the flavor by reducing the generation of volatiles, and increasing umami, richness, milk flavor and sweetness, but reducing sourness. These findings offer a new theoretical foundation for the industrial use of CO2 in raw milk.

Characterization and Toxic Potency of Airborne Particles Formed upon Waste from Electrical and Electronic Equipment Waste Recycling: A Case Study.

Manual dismantling, shredding, and mechanical grinding of waste from electrical and electronic equipment (WEEE) at recycling facilities inevitably lead to the accidental formation and release of both coarse and fine particle aerosols, primarily into the ambient air. Since diffuse emissions to air of such WEEE particles are not regulated, their dispersion from the recycling plants into the adjacent environment is possible. The aim of this interdisciplinary project was to collect and characterize airborne WEEE particles smaller than 1 μm generated at a Nordic open waste recycling facility from a particle concentration, shape, and bulk and surface composition perspective. Since dispersed airborne particles eventually may reach rivers, lakes, and possibly oceans, the aim was also to assess whether such particles may pose any adverse effects on aquatic organisms. The results show that WEEE particles only exerted a weak tendency toward cytotoxic effects on fish gill cell lines, although the exposure resulted in ROS formation that may induce adverse effects. On the contrary, the WEEE particles were toxic toward the crustacean zooplankter Daphnia magna, showing strong effects on survival of the animals in a concentration-dependent way.

Human Complement Inhibits Myophages against Pseudomonas aeruginosa.

Therapeutic bacteriophages (phages) are primarily chosen based on their in vitro bacteriolytic activity. Although anti-phage antibodies are known to inhibit phage infection, the influence of other immune system components is less well known. An important anti-bacterial and anti-viral innate immune system that may interact with phages is the complement system, a cascade of proteases that recognizes and targets invading microorganisms. In this research, we aimed to study the effects of serum components such as complement on the infectivity of different phages targeting Pseudomonas aeruginosa. We used a fluorescence-based assay to monitor the killing of P. aeruginosa by phages of different morphotypes in the presence of human serum. Our results reveal that several myophages are inhibited by serum in a concentration-dependent way, while the activity of four podophages and one siphophage tested in this study is not affected by serum. By using specific nanobodies blocking different components of the complement cascade, we showed that activation of the classical complement pathway is a driver of phage inhibition. To determine the mechanism of inhibition, we produced bioorthogonally labeled fluorescent phages to study their binding by means of microscopy and flow cytometry. We show that phage adsorption is hampered in the presence of active complement. Our results indicate that interactions with complement may affect the in vivo activity of therapeutically administered phages. A better understanding of this phenomenon is essential to optimize the design and application of therapeutic phage cocktails.

Deciphering the antifungal mechanism and functional components of cinnamomum cassia essential oil against Candida albicans through integration of network-based metabolomics and pharmacology, the greedy algorithm, and molecular docking

Ethnopharmacological relevanceFungal pathogens can cause deadly invasive infections and have become a major global public health challenge. There is an urgent need to find new treatment options beyond established antifungal agents, as well as new drug targets that can be used to develop novel antifungal agents. Cinnamomum cassia is a tropical aromatic plant that has a wide range of applications in traditional Chinese medicine, especially in the treatment of bacterial and fungal infections. Aim of the studyThe present study aimed to explore the mechanism of action and functional components of Cinnamomum cassia essential oil (CEO) against Candida albicans using an integrated strategy combining network-based metabolomics and pharmacology, the greedy algorithm and molecular docking. Materials and methodsCEO was extracted using hydrodistillation and its chemical composition was identified by GC-MS. Cluster analysis was performed on the compositions of 19 other CEOs from the published literature, as well as the sample obtained in this study. The damages of C. albicans cells upon treatment with CEO was observed using a scanning electron microscope. The mechanisms of its antifungal effect at a subinhibitory concentration of 0.1 × MIC were determined using microbial metabolomics and network analysis. The functional components were studied using the greedy algorithm and molecular docking. ResultsA total of 69 compounds were identified in the chemical analysis of CEO, which accounted for 90% of the sample. The major compounds were terpenoids (34.04%), aromatic compounds (4.52%), aliphatic compounds (0.9%), and others. Hierarchical cluster analysis of the compositions of 20 essential oils extracted from Cinnamomum cassia grown in different geographical locations showed a wide diversity of chemical composition with four major chemotypes. CEO showed strong antifungal activity and caused destruction of cell membranes in a concentration-dependent way. Metabolic fingerprint analysis identified 29 metabolites associated with lipid metabolism, which were mapped to 23 core targets mainly involved in fatty acid biosynthesis and metabolism. Six antifungal functional components of CEO were identified through network construction, greedy algorithm and molecular docking, including trans-cinnamaldehyde, δ-cadinol, ethylcinnamate, safrole, trans-anethole, and trans-cinnamyl acetate, which showed excellent binding with specific targets of AKR1B1, PPARG, BCHE, CYP19A1, CYP2C19, QPCT, and CYP51A1. ConclusionsThis study provides a systematic understanding of the antifungal activity of CEO and offers an integrated strategy for deciphering the potential metabolism and material foundation of complex component drugs.

Comparison of the potential of extracts from the flower, fruit pulp, and seed of Cassia fistula L. on MCF-7 breast cancer cell growth and cell migration

This study aimed to determine the anticancer effects of extracts prepared from various parts of Cassia fistula L. (CF), i.e., flower extract (FE), fruit pulp extract (FPE) and seed extract (SE), on MCF-7 breast cancer cells. The anticancer effects of the extracts were assessed for cell toxicity, cell proliferation, cell migration, cell apoptosis, and production of reactive oxygen species (ROS). Effective cancer treatments have focused on inhibiting epidermal growth factor receptor (EGFR) signalling. Thus, the expression of EGFR protein after extract-treated cells was also determined. Following a 72 incubation, high potential cytotoxicity on MCF-7 cells was observed after SE treatment, followed by FE and FPE treatment. FE, FPE, and SE significantly inhibited cell growth at concentrations of 500, 1,000, and 250 µg/mL, respectively. Also, FE, FPE, and SE markedly suppressed migration of MCF-7 cells at concentrations of 500, 500, and 100 µg/mL, respectively. These results can be concluded that SE had the highest potential anticancer effect on MCF-7 cells when compared with FE and FPE. Thus, SE might be a potential source of preventative and therapeutic agents against breast cancer. Since most anticancer drugs cause ROS production in cancer cells and it is known that ROS induce cell death; therefore, cell apoptosis and ROS formation induced by SE were further studied. The results showed SE induced MCF-7 cell apoptosis in a concentration-dependent way. SE caused a significant increase in ROS formation when compared with the control group. Western blot analysis showed low levels of EGFR protein expression after SE-treated cells at 1,000 mg/mL. Therefore, besides ROS formation, it may be concluded that the downregulation of EGFR protein expression is potentially one of the fundamental mechanisms driving the anticancer effects of SE.

Major phenolic compounds, antioxidant, antimicrobial, and cytotoxic activities of Selinum carvifolia (L.) collected from different altitudes in India.

Antibiotic resistance poses a serious threat to public health, raising the number of diseases in the community. Recent research has shown that plant-derived phenolic compounds have strong antimicrobial, antifungal, and cytotoxic properties against a variety of microorganisms and work as great antioxidants in such treatments. The goal of the current work is to evaluate the anticancerous, antibacterial, antifungal, antioxidant, and cytotoxicity activities in the extracts of the different plant parts (leaves, stems, and roots) of S. carvifolia (L.) L. This is a medicinally important plant and has been used for different kinds of diseases and ailments such as hysteria and seizures. The phenolic compounds from the different plant parts were analyzed using HPLC and the following were found to be present: chlorogenic acid, gallic acid, rutin, syringic acid, vanillic acid, cinnamic acid, caffeic acid, and protocatechuic acid. Gallic acid was found to have the highest concentration (13.93 mg/g), while chlorogenic acid (0.25 mg/g) had the lowest. The maximum TPC value, which ranged from 33.79 to 57.95 mg GAE/g dry extract weight, was found in the stem. Root extract with 9.4 mg RE/g had the greatest TFC level. In the leaf and stem extracts, the RSC ranged from 0.747 mg/mL to 0.734 mg/1 mL GE/g dry extract weight, respectively. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to measure in vitro antioxidant activity. In a concentration-dependent way, promising antioxidant activity was reported. Moreover, 3,5-dinitrosalicylic acid (DNSA) and the Folin-Ciocalteu phenol reagent technique were used to determine reducing sugar content and total phenolic content, respectively. Antibacterial activity against eight strains (MIC: 250-1,000 μg/mL) was analyzed, and the stem extract exhibited maximum activity. Antifungal activity was also assessed, and potent activity was reported especially in the extract obtained from the stem. Cytotoxicity was evaluated using an MTT assay in the A549 cell line, where different doses (0.0625, 0.125, 0.25, 0.5, and 1 mg/mL) of leaf, root, and stem extracts were used. Treatment with these extracts reduced the cell viability, indicating that S. carvifolia may possess anticancer potential, which can be of great therapeutic value.