The potential role of formononetin in cancer treatment: An updated review.

Currently, cancer is one of the main research topics, due to its high incidence and drug resistance to existing anti-cancer drugs. Formononetin, a natural product with phytoestrogenic properties and diverse biological functions, has attracted the attention of researchers working on anticancer drugs. Formononetin emerges as an intriguing bioactive substance compared to other isoflavones as it exhibits potent chemotherapeutic activity with less toxicity. Formononetin effectively plays a significant role in inhibiting cell proliferation, invasion, and metastatic abilities of cancer cells by targeting major signaling pathways at the junction of interconnected pathways. It also induces apoptosis and cell cycle arrest by modulating mediator proteins. It causes upregulation of key factors such as p-AKT, p38, p21, and p53 and downregulation of NF-κB. Furthermore, formononetin regulates the neoplastic microenvironment by inactivating the ERK1/2 pathway and lamin A/C signaling and has been reported to inactivate JAK/STAT, PKB or AKT, and mitogen-activated protein kinase pathways and to suppress cell migration, invasion, and angiogenesis in human cancer cells. To assist researchers in further exploring formononetin as a potential anticancer therapeutic candidate, this review focuses on both in vitro and in vivo proof of concept studies, patents, and clinical trials pertinent to formononetin's anticancer properties. Overall, this review discusses formononetin from a comprehensive perspective to highlight its potential benefits as an anticancer agent.

Antioxidant and antiproliferative activity of Basella alba against colorectal cancer.

Basella alba, a green leafy vegetable with remarkable nutraceutical potential is widely used since ancient times to maintain a healthy colon. This plant has been investigated for its medicinal potential due to the increase in young adult cases of colorectal cancer each year. This study was accomplished to investigate Basella alba methanolic extract (BaME) antioxidant and anticancer properties. BaME consisted of a substantial amount of both phenolic and flavonoid compounds which exhibited significant antioxidant reactivity. Both colon cancer cell lines experienced a cell cycle arrest at the G0/G1 phase after receiving treatment with BaME, which inhibited pRb and cyclin D1 and raised p21 expression levels. This was associated with the survival pathway molecule inhibition and downregulation of E2F-1. The results of the current investigation confirm that BaME inhibits CRC cell survival and expansion. To conclude, the bioactive principles in the extract act as potential antioxidants and antiproliferative agents against colorectal cancer.

A highly sensitive lateral flow immunoassay for the rapid and on-site detection of enrofloxacin in milk.

Enrofloxacin (ENR) is a veterinary antibiotic used to treat bacterial infections in livestock. It chiefly persists in foods and dairy products, which in turn pose severe risks to human health. Hence it is very important to detect the ENR in foods and dairy products to safeguard human health. Herein, we attempted to develop a single-step detection lateral flow immunochromatographic assay (LFIA) using gold nanoparticles (AuNPs) for the rapid and on-site detection of ENR in milk samples. An anti-enrofloxacin monoclonal antibody (ENR-Ab) was conjugated with AuNPs for the specific detection of ENR in milk samples. For sensitivity improvement, many optimization steps were conducted on LFIA test strips. The visual limit of detection (vLOD) was found to be 20 ng/ml with a cut-off value of 50 ng/ml in the milk samples. The obtained LOD and cut-off value were within the safety limit guidelines of the Ministry of food and drug safety, South Korea. The test strip showed negligible cross-reactivity with ENR analogs, and other components of antibiotics, this indicates the high specificity of the LFIA test strip towards ENR. The designed test strip showed good reliability. The visual test results can be seen within 10 min without the need for special equipment. Therefore, the test strip can be employed as a potential detection strategy for the qualitative on-site detection of enrofloxacin in milk samples.

Highly Specific Peptide-Mediated Cuvette-Form Localized Surface Plasmon Resonance (LSPR)-Based Fipronil Detection in Egg.

Herein, we have developed peptide-coated gold nanoparticles (AuNPs) based on localized surface plasmon resonance (LSPR) sensor chips that can detect fipronil with high sensitivity and selectivity. The phage display technique has been exploited for the screening of highly specific fipronil-binding peptides for the selective detection of the molecule. LSPR sensor chips are fabricated initially by attaching uniformly synthesized AuNPs on the glass substrate, followed by the addition of screened peptides. The parameters, such as the peptide concentration of 20 µg mL-1 and the reaction time of 30 min, are further optimized to maximize the efficacy of the fabricated LSPR sensor chips. The sensing analysis is performed systematically under standard fipronil solutions and spike samples from eggs. The developed sensor has shown excellent sensitivity towards both standard solutions and spike samples with limit of detection (LOD) values of 0.01 ppb, respectively. Significantly, the developed LSPR sensor chips offer distinct features, such as a facile fabrication approach, on-site sensing, rapid analysis, cost-effectiveness, and the possibility of mass production, in which the chips can be effectively used as a promising and potential on-site detection tool for the estimation of fipronil.

Novel organisation and regulation of the pic promoter from enteroaggregative and uropathogenic Escherichia coli.

The serine protease autotransporters of the Enterobacteriaceae (SPATEs) are a large family of virulence factors commonly found in enteric bacteria. These secreted virulence factors have diverse functions during bacterial infection, including adhesion, aggregation and cell toxicity. One such SPATE, the Pic mucinase (protein involved in colonisation) cleaves mucin, allowing enteric bacterial cells to utilise mucin as a carbon source and to penetrate the gut mucus lining, thereby increasing mucosal colonisation. The pic gene is widely distributed within the Enterobacteriaceae, being found in human pathogens, such as enteroaggregative Escherichia coli (EAEC), uropathogenic E. coli (UPEC) and Shigella flexneri 2a. As the pic promoter regions from EAEC strain 042 and UPEC strain CFT073 differ, we have investigated the regulation of each promoter. Here, using in vivo and in vitro techniques, we show that both promoters are activated by the global transcription factor, CRP (cyclic AMP receptor protein), but the architectures of the EAEC and the UPEC pic promoter differ. Expression from both pic promoters is repressed by the nucleoid-associated factor, Fis, and maximal promoter activity occurs when cells are grown in minimal medium. As CRP activates transcription in conditions of nutrient depletion, whilst Fis levels are maximal in nutrient-rich environments, the regulation of the EAEC and UPEC pic promoters is consistent with Pic's nutritional role in scavenging mucin as a suitable carbon source during colonisation and infection.

An Overview on Single-Cell Technology for Hepatocellular Carcinoma Diagnosis.

Hepatocellular carcinoma is a primary liver cancer caused by the accumulation of genetic mutation patterns associated with epidemiological conditions. This lethal malignancy exhibits tumor heterogeneity, which is considered as one of the main reasons for drug resistance development and failure of clinical trials. Recently, single-cell technology (SCT), a new advanced sequencing technique that analyzes every single cell in a tumor tissue specimen, aids complete insight into the genetic heterogeneity of cancer. This helps in identifying and assessing rare cell populations by analyzing the difference in gene expression pattern between individual cells of single biopsy tissue which normally cannot be identified from pooled cell gene expression pattern (traditional sequencing technique). Thus, SCT improves the clinical diagnosis, treatment, and prognosis of hepatocellular carcinoma as the limitations of other techniques impede this cancer research progression. Application of SCT at the genomic, transcriptomic, and epigenomic levels to promote individualized hepatocellular carcinoma diagnosis and therapy. The current review has been divided into ten sections. Herein we deliberated on the SCT, hepatocellular carcinoma diagnosis, tumor microenvironment analysis, single-cell genomic sequencing, single-cell transcriptomics, single-cell omics sequencing for biomarker development, identification of hepatocellular carcinoma origination and evolution, limitations, challenges, conclusions, and future perspectives.

Antimicrobial Resistance and Comparative Genome Analysis of Klebsiella pneumoniae Strains Isolated in Egypt.

Klebsiella pneumoniae is an important human pathogen in both developing and industrialised countries that can causes a variety of human infections, such as pneumonia, urinary tract infections and bacteremia. Like many Gram-negative bacteria, it is becoming resistant to many frontline antibiotics, such as carbapenem and cephalosporin antibiotics. In Egypt, K. pneumoniae is increasingly recognised as an emerging pathogen, with high levels of antibiotic resistance. However, few Egyptian K. pneumoniae strains have been sequenced and characterised. Hence, here, we present the genome sequence of a multidrug resistant K. pneumoniae strain, KPE16, which was isolated from a child in Assiut, Egypt. We report that it carries multiple antimicrobial resistance genes, including a blaNDM-1 carbapenemase and extended spectrum ß-lactamase genes (i.e., blaSHV-40, blaTEM-1B, blaOXA-9 and blaCTX-M-15). By comparing this strain with other Egyptian isolates, we identified common plasmids, resistance genes and virulence determinants. Our analysis suggests that some of the resistance plasmids that we have identified are circulating in K. pneumoniae strains in Egypt, and are likely a source of antibiotic resistance throughout the world.

The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids.

Whooping cough, or pertussis, is resurgent in numerous countries worldwide. This has renewed interest in Bordetella pertussis biology and vaccinology. The in vitro growth of B. pertussis has been a source of difficulty, both for the study of the organism and the production of pertussis vaccines. It is inhibited by fatty acids and other hydrophobic molecules. The AcrAB efflux system is present in many different bacteria and in combination with an outer membrane factor exports acriflavine and other small hydrophobic molecules from the cell. Here, we identify that the speciation of B. pertussis has selected for an Acr system that is naturally mutated and displays reduced activity compared to B. bronchiseptica, in which the system appears intact. Replacement of the B. pertussis locus with that of B. bronchiseptica conferred higher levels of resistance to growth inhibition by acriflavine and fatty acids. In addition, we identified that the transcription of the locus is repressed by a LysR-type transcriptional regulator. Palmitate de-represses the expression of the acr locus, dependent on the LysR regulator, strongly suggesting that it is a transcriptional repressor that is regulated by palmitate. It is intriguing that the speciation of B. pertussis has selected for a reduction in activity of the Acr efflux system that typically is regarded as protective to bacteria.