Comment in Curr Med Chem. 2022 Mar 4;29(8):1314-1315.

BACKGROUND: Transient Receptor Potential (TRP) Channels constitute a large family of non-selective permeable ion channels involved in the perception of environmental stimuli with a central and continuously expanding role in oral tissue homeostasis. Recent studies indicate the regulatory role of TRPs in pulp physiology, oral mucosa sensation, dental pain nociception and salivary gland secretion. This review provides an update on the diverse functions of TRP channels in the physiology of the oral cavity, with emphasis on their cellular location, the underlying molecular mechanisms and clinical significance. METHODS: A structured search of bibliographic databases (PubMed and MEDLINE) was performed for peer-reviewed studies on the function of TRP channels on oral cavity physiology in the last ten years. A qualitative content analysis was performed of screened papers and a critical discussion on the main findings is provided. RESULTS: TRPs expression has been detected in major cell types of the oral cavity, including odontoblasts, periodontal ligament, oral epithelial, salivary gland cells, and chondrocytes of temporomandibular joints, where they mediate signal perception and transduction of mechanical, thermal, and osmotic stimuli. They contribute to pulp physiology through dentin formation, mineralization, and periodontal ligament formation, along with alveolar bone remodeling in the dental pulp and periodontal ligament cells. TRPs are also involved in oral mucosa sensation, dental pain nociception, saliva secretion, swallowing reflex and temporomandibular joints' development. CONCLUSION: Various TRP channels regulate oral cavity homeostasis, playing an important role in the transduction of external stimuli to intracellular signals in a cell typespecific manner and presenting promising drug targets for the development of pharmacological strategies to manage oral diseases.

Triple-negative breast cancer (TNBC) is a highly resistant, lethal, and metastatic sub-division of breast carcinoma, characterized by the deficiency of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In women, TNBC shows a higher aggressive behavior with poor patient prognosis and a higher recurrence rate during reproductive age. TNBC is defined by the presence of epithelial- to-mesenchymal-transition (EMT), which shows a significant role in cancer progression. At the epigenetic level, TNBC is characterized by epigenetic signatures, such as DNA methylation, histone remodeling, and a host of miRNA, MiR-193, LncRNA, HIF- 2α, eEF2K, LIN9/NEK2, IMP3, LISCH7/TGF-β1, GD3s, KLK12, mediated regulation. These modifications either are silenced or activate the necessary genes that are prevalent in TNBC. The review is based on epigenetic mediated mechanistic changes in TNBC. Furthermore, Thymoquinone (TQ), Regorafenib, Fangjihuangqi decoction, Saikosaponin A, and Huaier, etc., are potent antitumor natural compounds extensively reported in the literature. Further, the review emphasizes the role of these natural compounds in TNBC and their possible epigenetic targets, which can be utilized as a potential therapeutic strategy in the treatment of TNBC.

BACKGROUND: Curcuminoids, flavoring, and coloring agents in food have potent antioxidant, anti-tumor activity, and anti-inflammatory effects. However, they are rapidly metabolized to lesser active metabolites. Therefore, various studies have been conducted to synthesize new and stable curcumin analogues with enhanced therapeutic activity. METHODS: Fluorinated curcumin compounds (2a-2f) were synthesized by Knoevenagel condensation between fluorobenzaldehydes (1a-1f) with curcumin. Fluorinated demethoxycurcumin (3a) was synthesized by condensation between demethoxycurcumin and 3,4-difluorobenzaldehyde (1f). The structures of these compounds were confirmed by FTIR, 1H-NMR, 13C-NMR, 19FNMR, and mass spectroscopy. Antiproliferative activities of these synthetic compounds were evaluated against breast cancer cells (4T1), melanoma cancer cells (B16F10), and normal cell lines (NIH 3T3) using MTT assay. The interaction of curcumin, 2f and 3a with several proteins (1HCL, 2ZOQ, 3D94, 5EW3, 4WA9, 1XKK, 6CCY) was investigated. The structural preservation of the epidermal growth factor receptor (EGFR) was investigated by molecular dynamics simulation. RESULTS: The spectroscopic data obtained confirmed the proposed structure of fluorinated analogues. The results showed that compounds 2f and 3a inhibited cancer cells proliferation significantly more than other compounds. Compounds 2f and 3a showed the highest affinity and lowest binding energy with EGFR. The binding energies were -7.8, -10, and - 9.8 kcal/mol for curcumin, 2f and 3a with EGFR, respectively. The molecular docking results demonstrated that compounds 2f and 3a were firmly bound in a complex with EGFR via the formation of a hydrogen bond. CONCLUSION: In summary, we found that fluorinated demethoxycurcumin and fluorinated curcumin induces cancer cell death and binds to EGFR with high affinity.

BACKGROUND: Rapid advancement in computing technology and digital information leads to the possible use of machine learning on breast cancer. OBJECTIVE: This study aimed to evaluate the research output of the top 100 publications and further identify a research theme of breast cancer and machine-learning studies. METHODS: Databases of Scopus and Web of Science were used to extract the top 100 publications. These publications were filtered based on the total citation of each paper. Additionally, a bibliometric analysis was applied to the top 100 publications. RESULTS: The top 100 publications were published between 1993 and 2019. The most productive author was Giger ML, and the top two institutions were the University of Chicago and the National University of Singapore. The most active countries were the USA, Germany, and China. Ten clusters were identified as both basic and specialised themes of breast cancer and machine learning. CONCLUSION: Various countries demonstrated comparable interest in breast cancer and machine-learning research. A few Asian countries, such as China, India and Singapore, were listed in the top 10 countries based on the total citation. Additionally, the use of deep learning and breast imaging data was trending in the past 10 years in the field of breast cancer and machine-learning research.

Comment in Curr Med Chem. 2022 Mar 4;29(8):1314-1315.

Comment in Curr Med Chem. 2022 Mar 4;29(8):1314-1315.

Viruses are a continuing threat to global health. The lack or limited therapeutic armamentarium against some viral infections and increasing drug resistance issues make the search for new antiviral agents urgent. In recent years, a growing literature highlighted the use of triazolopyrimidine (TZP) heterocycles in the development of antiviral agents, with numerous compounds that showed potent antiviral activities against different RNA and DNA viruses. TZP core represents a privileged scaffold for achieving biologically active molecules, thanks to: i) the synthetic feasibility that allows to variously functionalize TZPs in the different positions of the nucleus, ii) the ability of TZP core to establish multiple interactions with the molecular target, and iii) its favorable pharmacokinetic properties. In the present review, after mentioning selected examples of TZP-based compounds with varied biological activities, we will focus on those antivirals that appeared in the literature in the last 10 years. Approaches used for their identification, the hit-to-lead studies, and the emerged structure-activity relationship will be described. A mention of the synthetic methodologies to prepare TZP nuclei will also be given. In addition, their mechanism of action, the binding mode within the biological target, and pharmacokinetic properties will be analyzed, highlighting the strengths and weaknesses of compounds based on the TZP scaffold, which is increasingly used in medicinal chemistry.

Ultrasound is not only the most widely used medical imaging mode for diagnostics owing to its real-time, non-radiation, portable and low-cost merits, but also a promising targeted drug/gene delivery technique by producing a series of powerful bioeffects. The development of micron-sized or nanometer-sized ultrasound agents or delivery carriers further makes ultrasound a distinctive modality in accurate diagnosis and effective treatment. In this review, we introduce one kind of unique biogenic gas-filled protein nanostructures called gas vesicles, which present some unique characteristics beyond the conventional microbubbles. Gas vesicles can not only serve as ultrasound contrast agent with innovative imaging methods such as cross-amplitude modulation harmonic imaging, but also can further be adjusted and optimized via genetic engineered techniques. Moreover, they could not only serve as acoustic gene reporters, acoustic biosensors to monitor the cell metabolism, but also serve as cavitation nuclei and drug carrier for therapeutic purpose. We focus on the latest development and applications in the area of ultrasound imaging and targeted therapeutics, and also give a brief introduction to the corresponding mechanisms. In summary, these biogenic gas vesicles show some advantages over conventional MBs that deserve making more efforts to promote their development.

Comment in Curr Med Chem. 2022 Mar 4;29(8):1314-1315.

Nanotechnology is the process of modulating shape and size at the nanoscale to design and manufacture structures, devices, and systems. Nanotechnology's prospective breakthroughs are incredible, and some cannot even be comprehended right now. The blood-brain barrier, which is a prominent physiological barrier in the brain, limits the adequate elimination of malignant cells by preventing the concentration of therapeutic drugs at the target tissue. Nanotechnology has sparked interest in recent years as a way to solve these issues and improve drug delivery. Inorganic and organic nanomaterials were found to be beneficial for bioimaging approaches and controlled drug delivery systems. Brain cancer (BC) and Alzheimer's disease (AD) are two of the prominent disorders of the brain. Even though the pathophysiology and pathways for both disorders are different, nanotechnology with common features can deliver drugs over the BBB, advancing the treatment of both disorders. This innovative technology could provide a foundation for combining diagnostics, treatments, and delivery of targeted drugs to the tumour site, with further supervising the response, by designing and delivering materials by employing atomic and molecular elements. There is currently limited treatment for Alzheimer's disease, and reversing further progression is difficult. Recently, various nanocarriers have been investigated to improve the bioavailability and efficacy of many AD treatment drugs. Nanotechnology-assisted drugs can penetrate the BBB and reach the target tissue. However, further research is required in this field, to ensure the safety and efficacy of drug-loaded nanoparticles. The application of nanotechnology in the diagnosis and treatment of brain tumours and Alzheimer's disease is briefly discussed in this review.

Adenosine triphosphate (ATP) is one of the most important molecules of life, present both, inside the cells and extracellularly. It is essential building block for nucleic acids biosynthesis and crucial intracellular energy storage. However, one of the most interesting functions of ATP is the role of a signaling molecule. Numerous studies indicate the involvement of ATP-dependent pathways in maintaining the proper functioning of individual tissues and organs. Herein, the latest data indicating the ATP function in the network of intra- and extracellular signaling pathways including purinergic signaling, MAP kinase pathway, mTOR and calcium signaling are collected. The main ATP-dependent processes maintaining the proper functioning of the nervous, cardiovascular and immune systems, as well as skin and bones are summarized. The disturbances in the ATP amount, its cellular localization, or interaction with target elements may induce pathological changes in signaling pathways leading to the development of serious diseases. The impact of an ATP imbalance on the development of dangerous health dysfunctions such as neurodegeneration diseases, the cardiovascular diseases (CVDs), diabetes mellitus, obesity, cancers and the immune pathogenesis are discussed here.

Development of novel treatment methods for cancer are needed given limitations of current treatment methods, including side effects and chemotherapeutic resistance, providing new hope for cancer patients. Cancer is the second leading cause of global mortality. Curcumin, the active ingredient of turmeric, has been used since ancient times for various therapeutic purposes. Several studies have identified its activity against cancer. Despite the established anticancer activity of curcumin, its low aqueous solubility and bioavailability are barriers to its effectiveness. In an attempt to solve this problem, many studies have formulated curcumin nanofiber preparations using a variety of methods. Electrospinning is a simple and affordable method in the production of nanofibers. Studies have shown increased curcumin bioavailability in nanofibers resulting from their high surface/ volume ratio and porosity. We have undertaken a detailed review of studies on the anticancer effects of curcumin nanofibers. Curcumin acts by inhibition of various biological cancer pathways, including NF-κB, mTOR, complex I, cytokines, expression of p-p65, Ki67, and angiogenesis-associated genes. It also induces apoptosis through activation of caspase pathways and ROS production in cancer cells. Curcumin-loaded PLA50/PVP50/Cur15 nanofibers were investigated in breast cancer, one of the most studied cancers, and was shown to have significant effects on the widely used HeLa-cell line. Most of the studies that were undertaken have been performed in cell lines in vitro, while relatively few animal studies have been reported. More preclinical and clinical studies are needed to evaluate the effectiveness of curcumin nanofiber anticancer activity. Amongst studies undertaken a variety of curcumin nanofibers of various formulations were shown to suppress a variety of cancer types. Overall, curcumin nanofibers were found to be more efficient than free curcumin. Therefore, curcumin nanofibers provide cancer treatment that offers great potential for effective cancer management. Further studies with curcumin nanofibers both in vitro and in vivo have the potential to benefit cancer management.