New Drug Development

ABSTRACT: The current work presents a novel flexible multifunctional platform for biological interface applications. The use of titania nanotube arrays (TNAs) as a multifunctional material is explored for soft-tissue interface applications. In vitro biocompatibility of TNAs to brain-derived cells was first examined by culturing microglia cells-the resident immune cells of the central nervous system on the surface of TNAs. The release profile of an anti-inflammatory drug, dexamethasone from TNAs-on-polyimide substrates, was then evaluated under different bending modes...

Brain organoids provide a unique opportunity to model organ development in a system similar to human organogenesis in vivo. Brain organoids thus hold great promise for drug screening and disease modeling. Conventional approaches to organoid characterization predominantly rely on molecular analysis methods, which are expensive, time-consuming, labor-intensive, and involve the destruction of the valuable 3D architecture of the organoids. This reliance on end-point assays makes it challenging to assess cellular and subcellular events occurring during organoid development in their 3D context...

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD...

Interactions between biological systems and nanomaterials have become an important area of study due to the application of nanomaterials in medicine. In particular, the application of nanomaterials for cancer diagnosis or treatment presents a challenging opportunity due to the complex biology of this disease spanning multiple time and spatial scales. A system-level analysis would benefit from mathematical modeling and computational simulation to explore the interactions between anticancer drug-loaded nanoparticles (NPs), cells, and tissues, and the associated parameters driving this system and a patient's overall response...

Nerve agents are among the most deadly and lethal chemical warfare agents (CWAs). Rapid identification is crucial for specialized individuals to take action against dangerous drugs. This paper describes the synthesis and characterisation of a probe (MNFZ) based on the methoxy naphthalene-furoic hydrazide group. The probe rapidly (100 s) detects and quantifies the nerve-agent simulant diethyl chlorophosphate (DCP) in both solution and vapor phases. This sensor uses a new recognition center, furoic hydrazide, where the nitrogen atom of the imine group (CN) attacks the electrophilic core phosphorus atom of DCP, followed by the hydrolysis of the imine group in the acetonitrile (ACN) solution to produce the corresponding aldehyde MNPA...

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research...

Researchers in various fields continue to discover improved ways of local delivery of drugs to specific locations and try to increase the efficiency of these methods. Extensive research has been done on smart nano-biomaterials for drug delivery systems (DDS) in different dimensions. With the advancement of biomedical nanotechnology, conventional smart DDS with stimuli- responsive capability has been developed. Smart nano-biomaterials can respond to environmental changes caused by endogenous or exogenous elements: endogenous factors such as environmental pH, temperature gradient, enzymes, oxidation, and reduction potential...

Recently, we developed Research and Diagnostic Algorithm Rules (RADAR) to assess the clinical and pathway features of mood disorders. The aims of this paper are to review a) the methodology for developing continuous RADAR scores that describe the clinical and pathway features of schizophrenia, and b) a new method to visualize the clinical status of patients and the pathways implicated in RADAR graphs. We review how to interpret clinical RADAR scores, which serve as valuable tools for monitoring the staging of illness, lifetime suicidal behaviors, overall severity of illness, a general cognitive decline index, and a behavior-cognitive-psychosocial (BCPS) index that represents the "defect"; and b) pathway RADAR scores which reflect various protective (including the compensatory immune- inflammatory system) and adverse (including neuro-immune, neuro-oxidative, and neurotoxic biomarkers) outcome pathways...

BACKGROUND AND OBJECTIVE: Malignant ascites (MA) is common in patients with advanced cancer, and about 60% of patients with MA experience distressing symptoms. In addition, MA has been identified as a poor prognostic factor, therefore, making the management of MA an important issue. We aimed to review literature describing MA provide a narrative synthesis of relevant studies. METHODS: A literature search of articles published between 1971 and May 2023 was performed in PubMed, and Cochrane library using the words "ascites/malignant ascites" and the theme of each section...

In an acidic buffered solution, erythrosine B can react with amiodarone to form an association complex, which not only generates great enhancement in resonance Rayleigh scattering (RRS) spectrum of erythrosine B at 346.5 nm but also results in quenching of fluorescence spectra of erythrosine B at λemission  = 550.4 nm/λexcitation  = 528.5 nm. In addition, the formed erythrosine B-amiodarone complex produces a new absorbance peak at 555 nm. The spectral characteristics of the RRS, absorbance, and fluorescence spectra, as well as the optimum analytical conditions, were studied and investigated...

Ferroptosis is a type of regulated cell death hallmarked by iron-mediated excessive lipid oxidation. Over the past decade since the coining of the term ferroptosis, advances in research have led to the identification of intracellular processes that regulate ferroptosis such as GSH-GPX4 pathway and FSP1-coenzyme Q10 /vitamin K pathway. From a disease perspective, the involvement of ferroptosis in pathological conditions including kidney disease has attracted attention. In terms of renal pathophysiology, ferroptosis has been widely investigated for its involvement in ischemia-reperfusion injury, nephrotoxin-induced kidney damage and other renal diseases...

The delayed mucosal healing of tooth extraction sockets in diabetes has few known effective treatment strategies, and its underlying mechanism remains unknown. Senescent cells may play a pivotal role in this delay, given the well-established association between diabetes, senescent cells, and wound healing. Here, we demonstrated an increase in p21- or p16-positive senescent cells in the epithelial and connective tissues of extraction sockets in type 2 diabetic rats compared to those in control rats. Between 7 and 14 days after tooth extraction, a decrease in senescent cells and improvement in re-epithelialization failure were observed in the epithelium, while an increase in senescent cells and persistence of inflammation were observed in the connective tissue...

Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products...

Annual breast cancer (BCa) deaths have declined since its apex in 1989 concomitant with widespread adoption of hormone therapies that target estrogen receptor alpha (ERα), the prominent nuclear receptor expressed in ∼80% of BCa. However, up to ∼50% of ER + patients with high-risk disease experience post endocrine therapy relapse and metastasis to distant organs. The vast majority of BCa mortality occurs in this setting, highlighting the inadequacy of current therapies. Genomic abnormalities to ESR1, the gene encoding ERα, emerge under prolonged selective pressure to enable endocrine therapy resistance...

As there is lack of research on how drugs are presented in crime literature, we read nearly 25,000 pages of crime literature written between 1890 and 2023 to provide an overview on the pharmacological content in this genre. Correct presentation of pharmacological information decreased over time. Misconceptions about certain substances, especially narcotics and anesthetics appear in many of the analyzed examples. Also, in comparison with crime TV series, books are inferior in providing the reader with additional information and pharmacological plausibility...

Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (4a-d) and benzamides derivatives (5a-e) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and mass spectra; and various physicochemical properties were determined...

We introduce a new algorithm MaxCliqueWeight for identifying a maximum weight clique in a weighted graph, and its variant MaxCliqueDynWeight with dynamically varying bounds. This algorithm uses an efficient branch-and-bound approach with a new weighted graph coloring algorithm that efficiently determines upper weight bounds for a maximum weighted clique in a graph. We evaluate our algorithm on random weighted graphs with node counts up to 10,000 and on standard DIMACS benchmark graphs used in a variety of research areas...

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival...

Coumarins are heterocycles of great interest in the development of valuable active structures in chemistry and biological domains. The ability of coumarins to inhibit biofilm formation of Gram positive bacterium (Staphylococcus aureus), Gram negative bacterium (Escherichia coli) as well as the methicillin-resistant S. aureus (MRSA) has been previously described. In the present work, new hybrid coumarin-heterocycles have been synthesized via the reaction of coumarin-6-sulfonyl chloride and 6-aminocoumarin with different small heterocycle moieties...

High-fat diet (HFD) has long been recognized as risk factors for the development and progression of ulcerative colitis (UC), but the exact mechanism remained elusive. Here, HFD increased intestinal deoxycholic acid (DCA) levels, and DCA further exacerbated colonic inflammation. Transcriptome analysis revealed that DCA triggered ferroptosis pathway in colitis mice. Mechanistically, DCA upregulated hypoxia-inducible factor-2α (HIF-2α) and divalent metal transporter-1 (DMT1) expression, causing the ferrous iron ions accumulation and ferroptosis in intestinal epithelial cells, which was reversed by ferroptosis inhibitor ferrostatin-1...