Inhibitory Concentration Values Research Articles

A phase I clinical trial investigating the safety, tolerability, and pharmacokinetics of HX301 (narazaciclib), a novel multi-kinase inhibitor targeting CSF1R, CDK 4/6, and ARK5, in patients with advanced solid tumors.

e15106 Background: HX301 (narazaciclib) is a promising novel multi-kinase inhibitor with potent activity against Colony Stimulating Factor 1 Receptor (CSF1R), Cyclin-Dependent Kinase 4/6 (CDK4/6), and Aurora Kinase 5 (ARK5), with a half-maximal inhibitory concentration (IC50) values in 0.29-4.95 nM range. It is an oral bioavailable agent and has the ability to cross blood-brain barrier. Preclinical data have showed significant antitumor activities, warranting further clinical trials to evaluate the safety, and potential efficacy in human subjects. Methods: Utilizing the standard 3+3 design, the study aimed to evaluate the safety, tolerability and pharmacokinetics of ascending doses of HX301. Patients with heavily pretreated advanced solid tumors received HX301single agent via oral administration, with doses ranging from 40mg to 200mg once daily for the first 21 days of each 28-day cycle. Results: As of December 27, 2023, a total of 20 patients (5 males, 15 females) were enrolled in the study, with varying doses of HX301 administered: 40 mg (n=3), 80 mg (n=3), 120 mg (n=4), 160 mg (n=3), and 200 mg (n=7). The median age of the patients was 55 years, ranging from 30 to 71. Notably, 15 patients (75%) had metastatic breast cancers. Dose-limiting toxicities (DLTs) were observed in 2 patients in the 200 mg group. These included a Grade 4 increase in alanine aminotransferase (ALT) and a Grade 3 decrease in platelet counts with associated epistaxis, both of which resolved after discontinuation of treatment. The most common treatment-related adverse events (AEs) observed were elevated aspartate aminotransferase (AST) (65.0%), decreased white blood cell count (50%), decreased neutrophil count (50%), elevated ALT (45%), elevated creatine kinase (45%), and elevated creatinine (35%). Additionally, 4 patients experienced Grade 3 or higher treatment-related AEs, including 1 patient in the 160 mg group with Grade 3 elevated γ-glutamyl transferase and alkaline phosphatase, and 3 patients in the 200 mg group with Grade 4 elevated ALT and Grade 3 elevated AST and Dyspepsia, Grade 3 decreased neutrophil and platelet counts, and Grade 3 hyperglycemia. Notably, no AEs led to death. Among the 20 patients evaluable for tumor assessment using RECIST 1.1 by Investigators, 4 obtained stable disease, including 2 patients in the 200 mg group, 1 in the 120 mg group, and 1 in the 80 mg group. Furthermore, 1 patient with HR+ breast cancer in the 200 mg group received study drug for over a year and achieved prolonged stable disease for more than 12 months, highlighting a notable clinical outcome. Conclusions: HX301 at dose levels ranging from 40mg to 160mg was tolerable with a manageable toxicity profile. Further clinical studies are needed to explore the drug's anti-tumor activity, particularly in combination settings. Clinical trial information: NCT05731934 .

Exosome-Mediated Transfer of ALDH2 in Nasopharyngeal Carcinoma Cells Confers Increased Resistance to Paclitaxel Treatment.

Nasopharyngeal carcinoma (NPC) is an aggressive and highly metastatic malignant tumor. Despite recent therapeutic advances, resistance to Taxol (the generic name of paclitaxel) therapy remains a major challenge in clinical management. Therefore, it is imperative to explore the potential mechanisms of paclitaxel resistance in NPC. This study aimed to investigate the expression of aldehyde dehydrogenase 2 (ALDH2) in NPC cells and its critical role in paclitaxel resistance. Paclitaxel-resistant cell line CNE1/Taxol (CNE1-TR), a drug-resistant cell line, was established by exposing the CNE1 nasopharyngeal carcinoma cell line to progressively increasing concentrations of paclitaxel. Furthermore, we investigated the role of ALDH2 in paclitaxel resistance and the function of exosomes using cell culture, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), Cell Counting Kit-8 (CCK-8), and nanoparticle tracking analysis. The results showed that in the presence of paclitaxel, the CNE1-TR cells manifested higher survival rate and half-maximal inhibitory concentration (IC50) value compared to the parental cell line, indicating strong resistance to paclitaxel. CNE1-TR cells had significantly upregulated mRNA and protein levels of ALDH2. In addition, exosome analysis showed that CNE1-TR cells were able to deliver ALDH2 via exosomes, increasing paclitaxel resistance in the recipient cells. We observed that the ALDH2 expression levels and paclitaxel resistance in CNE1-TR cells were effectively reduced by blocking the release of exosomes. ALDH2 is not only a key molecular marker indicative of therapeutic efficacy, but also a potential therapeutic target for developing novel anticancer strategies. By blocking the exosomal transport of ALDH2 or directly inhibiting its activity, it may be possible to overcome paclitaxel resistance, thus improving the success rate of clinical treatment.

Pharmacological Properties of White Mulberry (Morus alba L.) Leaves: Suppressing Migratory and Invasive Activities Against A549 Lung Cancer Cells.

Morus alba known as a white mulberry is a medicinal plant that has been used in food ingredients and traditional medicine. M. alba leaves contain various bioactive phenolic compounds, in particular chlorogenic acid (CGA), which is a major bioactive ingredient. Their anticancer potency of M. alba leaf extracts derived from Soxhlet extraction was evaluated based on cytotoxicity and antimigratory and antiinvasive properties. The dichloromethane extract exhibited the highest nitric oxide radical scavenging activity with a half-maximal inhibitory concentration (IC50) value of 780μg/mL, promising cytotoxicity against HuCCA-1, MCF-7, and A-549 cells with IC50 values of 59.18, 62.20, and 103.25μg/mL, respectively. CGA selectively inhibited the growth of MCF-7 cells with an IC50 value of 26.75μg/mL and showed potent radical scavenging activity against DPPH radicals (IC50 = 18.85μg/mL). An ethanolic extract derived from the gradient Soxhlet extraction suppressed A549 lung cancer cell migration and invasion more effectively than CGA with no migratory inhibition effect on noncancerous HaCaT cells. Furthermore, the ethanolic extract and CGA accelerated HaCaT wound closure at 20µg/mL, which was the same as allantoin. Bioactive ingredients including triterpenes, steroids, phenolics, and flavonoids were mainly detected in all extracts. The highest content of CGA (52.23g/100g dry weight) was found in the ethanolic extract derived from the gradient Soxhlet extraction. These findings show the potency of the dichloromethane extract as a cytotoxic agent against various cancer types and the ethanolic extract as an antimetastatic agent by their antimigratory and antiinvasive activities.

The phenoxy-bearing naphthalimide substituted phthalocyanines: Photophysicochemical and biological properties

A new Si(IV) phthalocyanine (Pc) (1) derivative comprising axially phenoxy-bearing naphthalimide and peripherally t-butyl groups was synthesised and the photophysicochemical properties of this compound were investigated as an antioxidant and antimicrobial agent. Furthermore, the biological properties of the Si(IV) Pc compound (1) and its Zn(II) and Ga(III) Pc derivatives with a peripherally attached phenoxy-bearing naphthalimide group(2 and 3) were assessed in this study. While these compounds exhibited moderate antioxidant effects, their DNA nuclease activities were highly satisfactory. The compounds demonstrated effective antimicrobial activity, particularly following the photodynamic therapy. The most effective minimum inhibitory concentration value was obtained as 4 mg/L against E. faecalis and S. aureus. All compounds inhibited 100 % microbial cell viability at 125 mg/L. The biofilm formation ability of P. aeruginosa and S. aureus was significantly inhibited by all of the Pc compounds. Furthermore, experimental data were supported by TD-DFT calculations and NTO analyses, and the orbital densities of the compounds were shown.

P215 Effect of ivacaftor on the fractional inhibitory concentration values of antibiotic combinations used in the treatment of Pseudomonas aeruginosa in cystic fibrosis

P215 Effect of ivacaftor on the fractional inhibitory concentration values of antibiotic combinations used in the treatment of Pseudomonas aeruginosa in cystic fibrosis

New benzimidazole-oxadiazole derivatives as potent VEGFR-2 inhibitors: Synthesis, anticancer evaluation, and docking study.

We report herein, the design and synthesis of benzimidazole-oxadiazole derivatives as new inhibitors for vascular endothelial growth factor receptor-2(VEGFR-2). The designed members were assessed for their in vitro anticancer activity against three cancer cell lines and two normal cell lines; A549, MCF-7, PANC-1, hTERT-HPNE and CCD-19Lu. Compounds 4c and 4d were found to be the most effective compounds against three cancer cell lines. Compounds 4c and 4d were then tested for their in vitro VEGFR-2 inhibitory activity, safety profiles, and selectivity indices using the normal hTERT-HPNE and CCD-19Lu cell lines. It was determined that compound 4c was the most effective and safe member of the produced chemical family. Vascular endothelial growth factor A(VEGFA) immunolocalizations of compounds 4c and 4d were evaluated relative to control by VEGFA immunofluorescence staining. Compounds 4c and 4d inhibited VEGFR-2 enzyme with half-maximal inhibitory concentration values of 0.475 ± 0.021and 0.618 ± 0.028 µM, respectively. Molecular docking of the target compounds was carried out in the active site of VEGFR-2 (Protein Data Bank: 4ASD).

An anoikis-related gene signature predicts prognosis, drug sensitivity, and immune microenvironment in cholangiocarcinoma

BackgroundCholangiocarcinoma is a malignant invasive biliary tract carcinoma with a poor prognosis. Anoikis-related genes are prognostic features of a variety of cancers. However, the value of prognostication and therapeutic effect of anoikis-related genes in cholangiocarcinoma have not been reported. The aim of this research was developing an ARGs signature associated with cholangiocarcinoma patients. MethodsWe introduced transcriptome data to discover genes that were differentially expressed in cholangiocarcinoma. Subsequently, WGCNA was utilized to screen critical module genes in reference to anoikis. The univariate Cox, Lasso regression and Kaplan-Meier survival were executed to build a prognostic signature. We further performed gene functional enrichment, immune microenvironment and immunotherapy analysis between two risk subgroups. Finally, the pRRophetic algorithm was applied to compare the half inhibitory concentration value of several drugs. ResultsA grand total of 1844 genes with differential expression related to the cholangiocarcinoma patients were identified. Furthermore, we obtained 2678 key module genes related to anoikis. Then, a prognostic signature was developed using the 6 prognostic genes (FXYD2, PCBD1, C1RL, GMNN, LAMA4 and HACL1). Independent prognostic analysis showed that risk score and alcohol could function as separate prognostic variables. We found cetain distinction in the immune microenvironment between the two risk subgroups. Moreover, immunotherapy evaluation showed that the anoikis-related gene signature could be applied as a therapy predictor. Finally, Chemotherapeutic drug sensitivity results showed that the low-risk group responded better to bosutinib, gefitinib, gemcitabine, and paclitaxel, while the high-risk group responded better to axitinib, cisplatin, and imatinib. ConclusionThe prognostic signature comprised of FXYD2, PCBD1, C1RL, GMNN, LAMA4 and HACL1 based on anoikis-related genes was established, which provided theoretical basis and reference value for the research and treatment of cholangiocarcinoma.

Integrative multi-omics analysis reveals ortho-topolin riboside exhibits anticancer activity by regulating metabolic pathways in radio-resistant triple negative breast cancer cells

Radio-resistant triple negative breast cancer (TNBC) is resistant to conventional drugs and radiation therapy. ortho-topolin riboside (oTR) has been evaluated for its anticancer activity in several types of cancer cells. However, its anti-proliferative activity in radio-resistant TNBC cells has not yet been reported. Therefore, we investigated the anti-proliferative activity of oTR in radio-resistant TNBC cells, and performed metabolome, lipidome, transcriptome, and proteome profiling to reveal the mechanisms of the anticancer activity of oTR. oTR showed cytotoxicity against radio-resistant TNBC cells with an inhibitory concentration (IC50) value of 7.78 μM. Significantly decreased (p value < 0.05) basal and compensatory glycolysis were observed in the oTR-treated group than untreated group. Mitochondrial spare respiratory capacity, which is relevant to cell fitness and flexibility, was significantly decreased (p value < 0.05) in the oTR-treated group. The major metabolic pathways significantly altered by oTR according to metabolome, transcriptome, and proteome profiles were the glycerolipid/glycerophospholipid pathway (log2(FC) of MGLL = −0.13, log2(FC) of acylglycerol lipase = −1.35, log2(FC) of glycerol = −0.81), glycolysis (log2(FC) of EGLN1 = 0.16, log2(FC) of EGLN1 = 0.62, log2(FC) of glucose = −0.76, log2(FC) of lactate = −0.81), and kynurenine pathway (log2(FC) of KYNU = 0.29, log2(FC) of kynureninase = 0.55, log2(FC) of alanine = 0.72). Additionally, proline metabolism (log2(FC) of PYCR1 = −0.17, log2(FC) of proline = −0.73) was significantly altered in the metabolomic and transcriptomic profiles. The MAPK signaling pathway (log2(FC) of CCN1 = −0.15, log2(FC) of CCN family member 1 = −1.02) and Rap 1 signaling pathway (log2(FC) of PARD6B = −0.28, log2(FC) of PAR6B = −3.13) were also significantly altered in transcriptomic and proteomic profiles. The findings of this study revealed that oTR has anticancer activity in radio-resistant TNBC cells by affecting various metabolic pathways, suggesting the potential of oTR as a novel anticancer agent for radio-resistant TNBC patients.

A novel lactylation-related gene signature for effectively distinguishing and predicting the prognosis of ovarian cancer.

Lactylation has been found to regulate several types of biological processes in cancer. However, there is limited research on lactylation-related genes in predicting the prognosis of ovarian cancer (OC). This study aimed to explore the functional roles of lactylation-related genes in OC. Based on TCGA database, we obtained RNA sequencing data and clinical characteristics of patients with OC. Fourteen lactylation-related genes were screened for bioinformatic analysis in OC. Tumor classification of OC was constructed via a consistency cluster analysis. We examined the prognosis, immune-cell infiltration, and immunotherapy in relation to a lactylation-related model for OC. A total of 707 prognostic genes and 14 key lactylation-related genes (SNRPA1, MPHOSPH6, POLDIP3, RB1, AHNAK, MAGOHB, CALM1, EP300, HDAC1, HDAC2, HDAC3, SIRT1, SIRT2, and SIRT3) were identified in TCGA-OC patients. Based on 14 genes involved in lactylation, TCGA-OC patients were split into low-risk (G1) and high-risk (G2) groups. Downregulated differentially expressed genes (DEGs) in the low-risk G1 group were associated with thermogenesis, oxidative phosphorylation, neutrophil extracellular trap formation, and interleukin 17 (IL-17) signaling pathway, whereas upregulated DEGs were associated with proteoglycans in cancer, focal adhesion, Wnt signaling pathway, extracellular matrix (ECM)-receptor interaction, and the adherens junction. The immune activity of the low-risk G1 group was lower than that of the high-risk G2 group. Gemcitabine, bleomycin, and doxorubicin had lower half-maximal inhibitory concentration (IC50) values in the high-risk G2 patients with OC, while cisplatin and paclitaxel had higher IC50 values compared to the low-risk G1 patients. The prognosis of patients with OC was also predicted with the help of an eight-lactylation-related gene prognostic model, comprising SNRPA1, MPHOSPH6, POLDIP3, RB1, HDAC1, CALM1, HDAC2, and SIRT2. The lactylation-related genes are closely related to tumor classification and immunity in patients with OC. There was good prognostic predictive performance for OC based on a lactylation-related signature. Our findings may offer new insights into the diagnosis and treatment of OC.

Low Concentration of Wenyang Tonglin Decoction Promotes Conjugation and Transfer of Drug-Resistant Plasmids among Heterologous Strains.

To investigate the effect of low concentration of Wenyang Tonglin Decoction (WTD) on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism. Escherichia coli CP9 (R45) and Staphylococcus aureus RN450RF were cultured in medium containing WTD, and their minimum inhibitory concentration (MIC) values were obtained. Using promoter fusion technology, E. coli CP9 (R45) containing a promoter fusion was obtained. β-Galactosidase activity of TrfAp and TrbBp was tested, and the mRNA expression of regulatory factors (TrbA, KorA, and KorB) was detected by real-time fluorescent quantitative polymerase chain reaction. The MIC of E. coli CP9 (R45) was 400 g/L and that of S. aureus RN450RF was 200 g/L. When the drug concentration in the culture medium was 200 g/L, the highest number of conjugants was (3.47 ±0.20) × 107 CFU/mL At 90 h of conjugation, the maximum number of conjugants was (1.15 ±0.06) × 108 CFU/mL When the initial bacterial concentration was 108 CFU/mL, the maximum number of conjugants was (3.47 ± 0.20) × 107 CFU/mL. When the drug concentration was 200 g/L, the β-galactosidase activity of TrfAp and TrbBp significantly increased; the relative quantification of TrbA, KorA and KorB were significantly inhibited. Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.

Exploring Quinoxalinone Derivatives as Promising Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for Cancer Therapy

E GFR plays an extensive role in the signaling pathway such as proliferation, migration, invasion. However, the malfunctioning of the epidermal growth factor receptor (EGFR) is a crucial factor in cancer progression. The search for new kinase inhibitors is necessary due to the evolving nature of diseases and the emergence of resistant strains, prompting the need for novel compounds that can effectively target and inhibit specific kinases for therapeutic purposes. This study explores quinoxalinone derivatives, comprised of benzene and pyrazine aromatic rings, as novel potential EGFR kinase inhibitors for cancer therapy, fulfilling an essential need in targeted cancer treatments. We utilized molecular docking to examine 46 synthesized quinoxalinone derivatives for their interaction with the tyrosine kinase domain of EGFR. Fifteen compounds exhibited strong binding affinities. Notably, LS3c, MN333, and MN343 displayed significant inhibitory effects on A431 cells with half-maximum inhibitory concentration (IC50) values comparable to gefitinib, erlotinib, and afatinib in enzymatic kinase assays. Subsequent experiments revealed that LS3c and MN343 effectively inhibit EGFR-expressing cell lines with low hepatotoxicity. MN343, the most potent compound, was selected for molecular dynamic simulation to understand its interaction with the tyrosine kinase of EGFR. To investigate the interaction between MN343 and EGFR’s tyrosine kinase, MM-PBSA analysis identified key residues (L694, V702, L768, M769, and L820) crucial for interaction, highlighting the potential of MN343 as a clinical EGFR tyrosine kinase inhibitor. The need for discovering new kinase inhibitors arises from the dynamic nature of diseases and the appearance of resistant strains, emphasizing the requirement for innovative compounds capable of targeting and inhibiting specific kinases effectively for therapeutic applications.

Targeting canine mammary neoplastic epithelial cells with a reengineered anthrax toxin: first study.

Mammary tumors are the most frequent type of neoplasms in intact female dogs. New therapies that target neoplastic cells without affecting normal cells are highly sought. The Bacillus anthracis toxin has been reengineered to target tumor cells that express urokinase plasminogen activators and metalloproteinases. In previous studies carried out in our laboratory, the reengineered anthrax toxin had inhibitory effects on canine oral mucosal melanoma and canine osteosarcoma cells. In this study, five canine neoplastic epithelial cell lines (four adenocarcinomas and one adenoma) and one non-neoplastic canine mammary epithelial cell line were treated with different concentrations of reengineered anthrax toxin components. Cell viability was quantified using an MTT assay and half-maximal inhibitory concentration (IC50) values. Cell lines were considered sensitive when the IC50 was lower than 5000ng/ml. One canine mammary adenocarcinoma cell line and one mammary adenoma cell line showed significantly decreased viability after treatment, whereas the non-neoplastic cell line was resistant. We conclude that the reengineered anthrax toxin may be considered a targeted therapy for canine mammary neoplasms while preserving normal canine mammary epithelial cells.

Determination of antimicrobial and modulatory activity of bacterial resistance by nettle (Cnidoscolus urens) extracts in multiresistant bacteria isolated from bovine mastitis.

The present study aimed to evaluate the antimicrobial and modulating activity of the ethanol extract obtained from the leaves, stems, and roots of Cnidoscolus urens in multiresistant bacteria. The Minimum Inhibitory Concentration (MIC) values obtained for the extracts of leaves, stems, and roots were greater than 1024µg/mL for all isolates. In the antimicrobial resistance modulation test, the extract of the leaves of C. urens showed a better modulating effect than that of the stems and roots for gentamicin, highlighting the reduction of MIC for Escherichia coli, Lactococcus garvieae and Staphylococcus sciuri. For erythromycin, a reduction of MIC was observed in L. garvieae, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae. The extract from the leaves of C. urens has an important modulating effect on resistance in multiresistant bacteria, especially with gentamicin and erythromycin.

Therapeutic potential of multi-targeting phytochemicals derived from Apium graveolens ethanol extract in West Java, Indonesia against multidrug-resistant Pseudomonas aeruginosa

Abstract. Sufa HI, Kurniati I, Dermawan A, Abror YK, Indra AIN, Purkon DB. 2024. Therapeutic potential of multi-targeting phytochemicals derived from Apium graveolens ethanol extract in West Java, Indonesia against multidrug-resistant Pseudomonas aeruginosa. Biodiversitas 25: 2183-2190. This study aims to evaluate the antibacterial efficacy of Apium graveolens (AG) extract from West Java, Indonesia against MDR-P. aeruginosa species responsible for nosocomial infection. Several assessments of antibacterial activity in vitro were conducted, including the enumeration of bacterial colonies, the measurement of the inhibition zone by agar well diffusion, determination of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values, and the observation of cell damage using Scanning Electron Microscopy (SEM). The results have demonstrated that AG extract from West Java, Indonesia, possesses significant potential as an antimicrobial agent against MDR-P. aeruginosa. The Apium graveolens extract, at concentrations of 50, 100, and 200 mg/mL, reduced MDR-P. aeruginosa colonies by 59.3%, 65.7%, and 82%, respectively. The inhibition zone sizes ranged from 7 to 12 mm for 50 mg/mL, 8 to 16 mm for 100 mg/mL, and 16 to 17 mm for 200 mg/mL. The MIC values of 100 mg/mL for PA1 and PA3, 200 mg/mL for PA2, with an MBC value of 200 mg/mL for each test. Scanning electron microscope observation indicated that treatment with 100 mg/mL of AG extract caused significant damage to bacterial cells. In conclusion, A. graveolens extracts show promise as potential antibacterial agents against nosocomial infections caused by MDR-P. aeruginosa. Further research, including in vivo studies of the antibacterial mechanism of action, is warranted.

Extraction, Purification, and in vitro Antioxidant Activity Assessment of Total Flavonoids from the Aerial Parts of Tetrastigma hemsleyanum

Background The effective extractives of Tetrastigma hemsleyanum ( T. hemsleyanum) are useful, but this plant was not fully utilized in rural China. In this study, flavonoids from the aerial parts of T. hemsleyanum were extracted, and the purification method and the antioxidant capability were explored. Purpose This study is to explore the optimized purification method and the biological capability of the total flavonoids extracted from T. hemsleyanum. Materials and Methods The optimal extraction conditions were determined by single-factor and Box-Behnken design experiments. The antioxidant activities were assessed by analyzing their capability to scavenge 2,2-diphenyl-1-picrylhydrazyl and OH free radicals. Results and Discussion The optimal conditions for the extraction of the total flavonoids were as follows: ethanol volume fraction 60%, liquid-to-material ratios 35:1 mL/g, temperature 45℃, and time 85 min. The extraction rate of the total flavonoids was (3.59 ± 0.03)%. NKA-9 is an ideal macroporous resin for purification. The optimized purification process conditions of flavonoids were mass concentration of adsorption solution 1.50 mg/mL, pH value of adsorption solution 4.0, sample loading flow rate 2 BV/h, ethanol volume fraction in desorption process 60%, desorption flow rate 2 BV/h and elution volume 4 BV. After crude extracts were purified by NKA-9 macroporous resin, the content of the total flavonoids enhanced from (21.76 ± 0.18)% to (58.92 ± 0.22)%. The results of the experiments for antioxidant activity showed that the half maximal inhibitory concentration (IC50) values of the purified flavonoids extracted were 33.1and 42.7 µg/mL, respectively. Conclusion The results of this study indicated that the flavonoids in T. hemsleyanum have good antioxidant activity in vitro and deserve exploring in further pharmacological studies.

Secondary Metabolites from the Mangrove-derived Fungus Trichoderma sp.

Background:: Secondary metabolites from the mangrove-derived fungi have great potential to produce natural products with novel structures and significant biological activities. Objective:: The objective of this study was to isolate and identify the secondary metabolites from the mangrove-derived fungus Trichoderma sp. WHUF0342, and evaluate their antibacterial activities. Methods:: The compounds were isolated and purified by silica gel column chromatography, Sephadex LH-20 gel chromatography, and semi-preparative high-performance liquid chromatography (HPLC). Their structures were elucidated by comparing the NMR and MS spectroscopic data with those of literature. The antibacterial activity were evaluated by modified broth microdilution assay. Results:: Eight compounds were isolated from the fermented extracts of the fungus Trichoderma sp. WHUF0342 and identified as chaxine B (1), nafuredin (2), dichlorodiaportin (3), ferulaic acid (4), bis(2-ethylhexyl) benzene-1,2-dicarboxylate (5), methyl 4-hydroxyphenylacetate (6), 4- hydroxyphenyl acetate (7), and 4-hydroxyphenylethyl acetate (8). Chaxine B (1) showed antibacterial activity against the phytopathogenic bacterium Ralstonia solanacearum with a minimum inhibitory concentration (MIC) value of 16 μg/mL. The antibacterial activity against plant pathogen of compound 1 was reported for the first time in this study. Conclusion:: This study not only enriched the secondary metabolites of mangrove-derived fungi but also provided a valuable resource for the prevention of agricultural pathogen infections.

New Schiff bases and their vanadium complexes: Synthesis, characterization, and biological assessment for antibacterial and antiviral action

From the perspective of possible antiviral and antibacterial activity of vanadium‐based complexes, we report the synthesis of new Schiff base ligand (L4) and a new Schiff‐base‐vanadium complex (C2). Both the ligand and the complex were characterized by Fourier transform infrared spectroscopy and Nuclear magnetic resonance techniques. Single‐crystal X‐ray Diffraction analysis has been used to confirm the structure of ligand L4 and complex C2. In addition, L1–4 and C1–3 were tested for their antibacterial effects against Escherichia coli and Staphylococcus aureus. Among the compounds, L2 demonstrated the most potent inhibition of both bacteria, exhibiting the lowest values for minimum inhibitory concentration (CMI) and minimum bactericidal concentration (CMB) (CMI = 0.16, CMB = 0.31 against E. coli, and CMI = CMB = 0.16 against S. aureus). Additionally, L2 produced the largest inhibition zones with diameters of 15.5 ± 0.15 against E. coli and 14.5 ± 0.04 against S. aureus. Furthermore, the antiviral efficacy of L1, L2, L4, C1, C2, and C3 against RNA viruses was assessed. C2 and C3 exhibited the most potent antiviral activity among the tested compounds.

Antimicrobial mechanism of morusin against Bacillus cereus and its potential as an antimicrobial agent

Bacillus cereus, a food-borne pathogen, threatens human health and food safety. The quest for biologically active substances from natural sources acting as antimicrobial agents for the replacement of antibiotics and chemical additives has received increasing attention. In this study, the antimicrobial mechanism of morusin against B. cereus was outlined, as well as its function as a food supplement to extend the shelf-life of skimmed milk was assessed. Our findings demonstrated that the minimum inhibitory concentration (MIC) value of morusin against B. cereus was 2.25 μg/mL, inhibiting biofilm formation and reducing intracellular ATP and membrane depolarization by disturbing the permeability of the B. cereus cytoplasmic membrane. Damage or collapse of B. cereus cell membranes produced by morusin was identified using the field gun scanning electron microscope (FEG-SEM). Transcriptomic assessment indicated that the two-component system of B. cereus (narG, narH, narI, phoP, phoR, motA) responded positively to morusin within an adverse environment. Moreover, several genes associated with cell membrane and cell wall generation (murA, murB, ddlB) and amino acid metabolism (argF, argH, BCN_RS02850) were significantly downregulated, potentially accelerating the death of B. cereus. In addition, metabolomic investigation suggested that morusin restricted pyruvate metabolism, cysteine and methionine metabolic pathways, and disturbed the intracellular amino acid metabolism of B. cereus. Ultimately, 4.5 μg/mL of morusin was determined to significantly inhibit the growth of B. cereus within skimmed milk. Overall, morusin can be utilized as a natural antimicrobial agent for regulating B. cereus contamination in skimmed milk.

FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098-3.97 μM (0.066-2.68 μg mL-1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Molecular Markers and Antimicrobial Resistance Patterns of Extraintestinal Pathogenic Escherichia coli from Camel Calves Including Colistin-Resistant and Hypermucoviscuous Strains.

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are capable of causing various systemic infections in both humans and animals. In this study, we isolated and characterized 30 E. coli strains from the parenchymatic organs and brains of young (<3 months of age) camel calves which died in septicemia. Six of the strains showed hypermucoviscous phenotype. Based on minimum inhibitory concentration (MIC) values, seven of the strains were potentially multidrug resistant, with two additional showing colistin resistance. Four strains showed mixed pathotypes, as they carried characteristic virulence genes for intestinal pathotypes of E. coli: three strains carried cnf1, encoding cytotoxic necrotizing factor type 1, the key virulence gene of necrotoxigenic E. coli (NTEC), and one carried eae encoding intimin, the key virulence gene of enteropathogenic E. coli (EPEC). An investigation of the integration sites of pathogenicity islands (PAIs) and the presence of prophage-related sequences showed that the strains carry diverse arrays of mobile genetic elements, which may contribute to their antimicrobial resistance and virulence patterns. Our work is the first to describe ExPEC strains from camels, and points to their veterinary pathogenic as well as zoonotic potential in this important domestic animal.