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.

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.

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.

Simple and rapid detection of ractopamine in pork with comparison of LSPR and LFIA sensors.

This study developed a simple and rapid strategic technique to detect ractopamine (chemical growth-promoting agent) in pork. Two highly sensitive and specific gold nanoparticle-based portable sensors, i.e., localized surface plasmon resonance (LSPR) sensors, and lateral flow immunoassay (LFIA) strips were developed to detect veterinary drug residues in food products, that have detrimental effects on humans. Optimization studies were conducted on several sensor devices to improve sensitivity. Each sensor comprised functionalized gold nanoparticles conjugated with ractopamine antibodies. The LSPR sensor chip achieved excellent detection sensitivity = 1.19 fg/mL and was advantageous for quantitative analysis due to its wide dynamic range. On the other hand, LFIA strips provided visual test confirmation and achieved 2.27 ng/mL detection sensitivity, significantly less sensitive than LSPR. The complementary sensors help overcome each other's shortcomings with both the techniques offering ease of use, affordability and rapid diagnosis. Thus, these sensors can be applied on-site for routine screening of harmful drug residues in pork meat. They also provide useful direction for advanced technologies to enhance assay performance for detecting various other food drug contaminants.

Targeting Key Transcription Factors in Hepatocellular Carcinoma.

Liver cancer is classified amongst the foremost causes of tumor-associated deaths around the world. The liver cancer death is more common in men compared to females with overall death rate being doubled from 1980-2017. A primary pathological category of liver cancer is the hepatocellular carcinoma (HCC), which accounts for nearly 80% of all liver cancers. Since HCC is mainly diagnosed at advanced stages, making the surgical and locoregional treatments extremely difficult. Dysregulation of transcription factors, the central modulators of normal and transformed tumorous cellular processes such as STAT-1, STAT-3, NF-κB, Ap1, and HIF-1α are known to be activated in HCC invasion, progression, and metastasis are highlighted in this review. The recently approved drugs, such as sorafenib regorafenib, lenvatinib, and cabozantinib, are tyrosine kinase inhibitors (TKIs), which completely reduce HCC progression by targeting transcription factors are discussed.

Antioxidant and anti-aging potential of a peptide formulation (Gal2-Pep) conjugated with gallic acid.

Skin is highly vulnerable to premature aging due to external stress, therefore, in this study, a peptide formulation, (galloyl)2-KTPPTTP (Gal2-Pep) was synthesized by combining TPPTTP peptide, and gallic acid (GA). All peptides were synthesized on 2-chlorotrityl chloride resin using solid-phase peptide synthesis (SPPS), and analyzed on an electrospray ionization (ESI)/quadrupole-time-of-flight (Q-TOF) tandem mass spectroscopy (MS) system. Initially, Gal2-Pep showed no toxicity below the concentration 100 µM with cell survival rate of 88% for keratinocytes and fibroblasts. The reactive oxygen species (ROS) scavenging activity of Gal2-Pep was more stable compared to GA alone; and after four weeks at room temperature, its ROS scavenging activity remained higher than 50%. Moreover, the peptide formulation, Gal2-Pep also exhibited elastase inhibitory effect in CCD-1064Sk fibroblast cells. Based on the results of RT-qPCR, it was proved in this study that Gal2-Pep increased the expression of PGC-1α to prevent oxidative stress, and validated its potential as an anti-aging agent through increasing the expression of type I collagen and by decreasing the expression of matrix metalloproteinase-1 (MMP1). The findings obtained reinforce the suggestion that the peptide formulation synthesized in this study could be used as a natural antioxidant and anti-aging agent for its cosmetic applications.

Resveratrol binds and activates RKIP protein in colorectal cancer.

Raf-1 kinase inhibitory protein (RKIP) acts as a tumor cell metastasis suppressor and prognostic indicator for survival in various cancers. Its use is predicted to improve therapy for various malignancies, including colorectal cancer (CRC). RKIP, frequently denoted as phosphatidylethanolamine-binding protein 1, is expressed in all normal mammalian tissues. RKIP functions as an inhibitor of the Raf-1, PI-3K, and MAP kinase (MAPK) pathways. In this study, we found that resveratrol induced the expression of RKIP at protein levels. To elucidate the structural basis of the interaction between resveratrol and RKIP, we performed computational studies that explore the binding affinity and ligand efficacy of resveratrol against RKIP. This study reveals the prognostic significance of RKIP metastasis suppressor activity against CRC and its structural arrangements during drug-target interactions.

Resveratrol binds and inhibits transcription factor HIF-1α in pancreatic cancer.

Hypoxia-inducible factor-1 alpha (HIF-1α) has been recognized as one of the essential regulators that is expressed in greater levels in pancreatic cancer (PC) and is connected with poor prognosis. Resveratrol was identified as a natural compound with many biological functions, with anti-inflammatory, antioxidant, and anticancer effects that inhibit the proliferation and progression of PC cells caused by HIF-1α. The current investigation explored the binding affinity and ligand efficacy of resveratrol against HIF-1α using an in silico approach, and the execution of molecular dynamics simulation (MDS) increased the prediction precision of these outcomes. This is the first study that provides an in silico characterization of the interaction between resveratrol and HIF-1α and its spatial structural arrangements in pancreatic cancer therapy, providing an in-depth analysis of their drug target interactions.

Colorectal Cancer Biology, Diagnosis, and Therapeutic Approaches.

Colorectal cancer (CRC) is the second most diagnosed disease worldwide. It is the fourth leading cause of cancer related mortalities. Higher probability for the occurrence of CRC is due to western lifestyle, age, and personal history of chronic diseases. The development of CRC is a multistep process that includes a sequence of genetic, histological, and morphological alterations that accumulate over time. Furthermore, depending on the origin of mutations, CRC can be classified as familial, sporadic, and inherited, based on which a therapeutic plan is created for a CRC patient. These mutations cause chromosomal alterations and translocations in genes that lead to microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN). The mutations affect dysregulation of various pathways that are responsible for cancer progression. They include the PI3K/Akt, Wnt, TP53, and MAPK pathways. Mutated genes, such as KRAS, PTEN, SMAD4, BRAF, and PTEN, are employed as predictive biomarkers for early diagnosis. The conventional therapies of CRC start with surgical resection followed by adjuvant therapies, such as radiotherapy and chemotherapy. Researchers are now developing therapies that combine triplet drugs to overcome the hurdle of multidrug resistance (MDR). The combination of chemotherapy with immunotherapy to target the dysregulated proteins, such as EGFR and VEGFR is found efficient for advanced mCRC therapy. Researchers are now developing personalized medicines by detecting and validating key biomarkers to understand the mechanism of MDR and toxicity. In this review, we address genetic alterations, current data on biomarkers, and novel therapeutic approaches for the treatment of CRC.

The role of adiponectin in obesity-associated female-specific carcinogenesis.

Adipose tissue is a highly vascularized endocrine organ, and its secretion profiles may vary with obesity. Adiponectin is secreted by adipocytes that make up adipose tissue. Worldwide, obesity has been designated a serious health problem among women and is associated with a variety of metabolic disorders and an increased risk of developing cancer of the cervix, ovaries, uterus (uterine/endometrial), and breast. In this review, the potential link between obesity and female-specific malignancies is comprehensively presented by discussing significant features of the intriguing and complex molecule, adiponectin, with a focus on recent findings highlighting its molecular mechanism of action in female-specific carcinogenesis.

MicroRNAs as biomarkers and prospective therapeutic targets in colon and pancreatic cancers.

Colon and pancreatic cancers have high mortality rates due to early metastasis prior to the onset of symptoms. Screening tests for colorectal cancer are invasive and expensive. No effective screening is available for pancreatic cancer. Identification of biomarkers for early detection in both of these cancers is being extensively researched. MicroRNAs (miRNA) are small non-coding molecule biomarkers that regulate cancers. Measurement of miRNAs in pancreatic fluid or blood could be a preferred non-invasive screening method. The regulation of colon and pancreatic cancers by miRNA is complex. miRNA play a central role in inflammation, invasiveness, and tumor progression in these two cancers, as well as regulation of the NF-κB pathway. miRNA's evolving role in screening is also reviewed.

Role of adiponectin in obesity related gastrointestinal carcinogenesis.

Adiponectin is produced in the white adipose tissue and is known to have anti-metabolic and anti-inflammatory properties. Serum/plasma adiponectin levels depend on diet, physical activity, and inheritance. Epidemiologic observations suggest a potential link between obesity and gastrointestinal malignancies. Low levels of adiponectin, which are known to occur in obesity, may contribute to the high incidence of cancer in this population. This review discusses the biochemical and molecular evidence regarding the relationship between adiponectin and gastrointestinal carcinogenesis and provides several future perspectives on the role of adiponectin as a target for prevention and therapy.

The impact of curcumin on breast cancer.

Curcumin, the active ingredient of turmeric (curry spice), is believed to be associated with reducing the incidence of breast cancers in Asian countries. Anti-cancer efficacy of curcumin and analogs has been tested in pre-clinical studies in some cancer models including breast cancer. These studies reported promising results in inhibiting human cancer cell proliferation and tumorigenesis in animal models. Both in vitro and in vivo studies have shown that curcumin and its analogs target critical genes associated with angiogenesis, apoptosis, cell cycle, and metastasis. The inhibition of human breast cancer cell growth by curcumin is mediated via certain signaling cascades including the modulation of the NF-κB signaling pathway. Epidemiological and experimental data also demonstrated the efficacy of curcumin in chemoprevention and reversing chemo-resistance of tumors of certain cancers. This review summarizes the studies revealing the preventive and therapeutic effects of curcumin and its analogs with an emphasis on multi-targeted biological and molecular effects in a breast cancer model.