Development and Discovery of a Selective Degrader of Casein Kinases 1 δ/ε.

Members of the casein kinase 1 (CK1) family have emerged as key regulators of cellular signaling and as potential drug targets. Functional annotation of the 7 human isoforms would benefit from isoform-selective inhibitors, allowing studies on the role of these enzymes in normal physiology and disease pathogenesis. However, due to significant sequence homology within the catalytic domain, isoform selectivity is difficult to achieve with conventional small molecules.

Enzymatic Interesterification of Cold-Pressed Maqui ( (Mol.) Stuntz) Seed Oil and Belly Oil from Rainbow Trout () Through Supercritical CO.

A new antioxidant lipid (AL) was synthesized from rainbow trout () belly oil and cold-pressed maqui (CPM) ( (Mol.) Stuntz) seed oil via enzymatic interesterification using in supercritical CO medium. A Box-Behnken design with 15 experiments was employed, with the independent variables being the following: belly oil/CPM oil ratio (10/90, 50/50, and 90/10, /), supercritical CO temperature (40.

Multiomics Analysis of Molecules Associated with Cancer in Mesenchymal-Stem-Cell-(MSC)-Derived Exosome-Treated Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer in humans, with an increasing incidence worldwide. The current study aimed to explore the molecular mechanisms that inhibit the proliferation of HepG2 cells, a hepatoblastoma-derived cell line. MSC-derived exosomes (UC-MSCs) were prepared with a median particle size (N50) of 135.

Etomoxir suppresses the expression of PPARgamma2 and inhibits the thermogenic gene induction of brown adipocytes through pathways other than β-oxidation inhibition.

Brown adipocytes are characterized by a high abundance of mitochondria, allowing them to consume fatty acids for heat production. Increasing the number of brown adipocytes is considered a promising strategy for combating obesity. However, the molecular mechanisms underlying their differentiation remain poorly understood.

Immune checkpoint inhibitor-associated diabetic ketoacidosis and insulin-dependent diabetes: a case report.

Background: Immunotherapy, including the use of immune checkpoint inhibitors such as nivolumab, is increasingly common in cancer treatment and can lead to various immune-related adverse effects, including rare cases of diabetic ketoacidosis. This case report highlights an unique instance of nivolumab-induced diabetic ketoacidosis in a patient without prior history of diabetes, emphasizing the importance of careful monitoring even in those without traditional risk factors.

Case Presentation: We report a case of a 70-year-old Caucasian male with metastatic esophageal adenocarcinoma who developed diabetic ketoacidosis 3 weeks after stopping nivolumab therapy.

Association between prenatal tobacco exposure and attention-deficit/hyperactivity disorder related characteristics at 6 and 8 years: a birth cohort in Japan.

Objectives: To examine the association between maternal plasma cotinine concentrations during pregnancy and attention-deficit/hyperactivity disorder (ADHD) related characteristics in children.

Design: Prospective birth cohort study from the Hokkaido Study on Environment and Children's Health.

Setting: Hokkaido, Japan.

The second phase of tumor invasion driven by immune cells: A study on doxorubicin-loaded PLG nanoparticles.

Poly(lactide-co-glycolide) (PLG) nanoparticles loaded with doxorubicin have reached phase-I clinical trials for treating advanced solid tumors. This study explores cell hitchhiking, where nanoparticles associate with blood cells and investigates the impact on pharmacokinetics and tumor migration. Previous findings highlighted the early post-injection phase dominated by nonspecific nanoparticle-cell interactions and burst release.

Phytochemical analysis of bioactive compounds in (Cooke & Massee) Priest mushrooms: potential applications in medicine and biotechnology.

Mushrooms have proven to be a valuable source of diverse bioactive compounds that can hold substantial potential for preventing and managing various diseases. This research focused on examining the numerous bioactive compounds found in () (Cooke & Massee) Priest mushrooms, particularly those obtained from ethyl acetate and dichloromethane extracts. Polyphenols, flavonoids, tannins, and alkaloids were also evaluated by chemical analysis.

TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent Antimalarial Activity and a High Barrier to Resistance.

Malaria continues to pose a significant burden on populations in endemic areas and requires innovative treatment options. Here, we report the synthesis and preclinical evaluation of the novel 3-hydroxypropanamidine (HPA) , which shows excellent antiplasmodial activity against drug-sensitive and -resistant strains. Moreover, in various human cell lines, the compound shows no cytotoxicity and excellent parasite selectivity.

Isolation, Structure Elucidation, and Bioactivity Evaluation of Two Alkaloids From H. Stem: A Traditional Medicinal Spice and Its Chemico-Pharmacological Aspects.

Bangladesh is endowed with an abundance of excellent medicinal plant resources. A well-known traditional medicinal plant H. from the Piperaceae family is rich in bioactive phytochemicals that have antidiarrheal, antimicrobial, analgesic, antioxidant, anticancer, and cytotoxic effects.

Navigating green synthesized metal-based nanoparticles as anti-inflammatory agent - Comprehensive review.

The biosynthesis of nanomaterials is a vast and expanding field of study due to their applications in a variety of fields, particularly the pharmaceutical and biomedical fields. Various synthetic routes, including physical and chemical methods, have been developed in order to generate metal nanoparticles (NPs) with definite shapes and sizes. In this review, focused on the recent advancements in the green synthetic methods for the generation of silver, zinc and copper NPs with simple and eco-friendly approaches and the potential of the biosynthesized metal and metal oxide NPs as alternative and therapeutic agent for the treatment of inflammatory diseases.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

New benzimidazole-indole-amide derivatives as potent α-glucosidase and acetylcholinesterase inhibitors.

New derivatives 6a-m with benzimidazole-indole-amide scaffold were developed, synthesized, and assessed for potential inhibitory effects on α-glucosidase and acetylcholinesterase (AChE). These compounds were synthesized by various amine derivatives. With the exception of two compounds, the α-glucosidase inhibitory activities of the title derivatives were more than that of the positive control acarbose.

Arketamine alleviates cognitive impairments and demyelination in mice with postoperative cognitive dysfunction via TGF-β1 activation.

Postoperative cognitive dysfunction (POCD) is characterized by a decline in cognitive functions, including memory, attention, and executive abilities, following surgery, with no effective therapeutic drugs currently available. Arketamine, the (R)-enantiomer of ketamine, has shown promise in mitigating cognitive deficits in animal models. In this study, we investigated whether arketamine could ameliorate cognitive deficits in a mouse model of POCD, with a focus on the role of transforming growth factor (TGF)-β1 in its effects.

Optimization of adsorption performance by mesoporous materials developed from local clays and zeolite. Application in the treatment of real pharmaceutical effluents.

The treatment of effluents from the pharmaceutical industry currently remains a major challenge due to their impact on the environment and public health along with the cost of treatments. Considering these issues, our work focused on the development of materials with effective adsorption properties to treat industrial effluents based on locally available and inexpensive clays and zeolite. Local Algerian kaolin (Djebel Debbagh), palygorskite (Ghoufi) and zeolite (Tinbdar) were treated thermally and chemically prior to synthesis into mesoporous materials of hexagonal structure using pluronic P123 as surfactant.

Cognitive-enhancing effect of fruit on scopolamine-induced cognitive impairment in rats: metabolite profiling, , and investigations.

Many plants are reported to enhance cognition in amnesic-animal models. The metabolite profile of fruit methanolic extract (CDFME) was characterized by LC-QTOF-MS/MS, and its total phenolics content (TPC) and total flavonoids content (TFC) were determined. In parallel, its cognitive-enhancing effect on scopolamine (SCOP)-induced AD in rats was evaluated.

Chemical composition, antimicrobial, and antioxidant properties of essential oils from asso. and caball. from Morocco: and evaluation.

Introduction: Morocco is home to a remarkable diversity of flora, including several species from the Artemisia genus. This study aims to thoroughly examine the chemical composition of essential oils derived from Artemisia species and assess their antibacterial and antioxidant properties through in vitro experiments and in silico simulations.

Methods: Samples of Artemisia herba-alba Asso.

Novel flame retardants (NFRs) in e-waste: Environmental burdens, health implications, and recommendations for safety assessment and sustainable management.

Novel flame retardants (NFRs) have emerged as chemicals of environmental health concern due to their widespread use as an alternative to polybrominated diphenyl ethers (PBDE) in electrical and electronic devices. Humans and ecosystems are under threat because of e-waste recycling procedures that may emit NFRs and other anthropogenic chemicals into the e-waste workplace and the surrounding environment. The individual toxicity of NFRs including novel brominated flame retardants (NBFRs), their combined effects and the underlying mechanisms of toxicity have remained poorly understood.

Design and Characterization of Novel Naphthalimide Fluorescent Probe for HS Detection in Human Serum.

In this work, a novel fluorescent probe (compound 2) based on the Intramolecular charge transfer (ICT) mechanism was designed and successfully applied to determine HS in human serum. Fluorophore 1,8-naphthalimide was chosen, while the azide group was the recognition group for HS determination. By introducing p-toluidine moiety on the imide part of the molecule, a donor-acceptor (D-A) conjugated system was formed.

Water-Induced Turn-on of Lanthanide Photoluminescence Emission and Application in Colorimetric Sensing of Trace Water.

To examine the water-induced photoluminescence turn-on and its potential application in trace water sensing, a new series of [Ln(dmba)(HO)]·2HO, where Ln = La (), Pr (), Nd (), Sm (), Eu (), Gd (), Tb (), Dy (), Ho (), and Er (), were synthesized using dimethoxybenzoic acid (Hdmba). Their single-crystal structures and thermal and chemical robustness were investigated, and the effects of lanthanide contraction and noncovalent interactions were discussed. The photoluminescence and colorimetric properties of - were investigated.

An Automated Low-Cost Solution for Creating a Multiple-Step Thermal Gradient to Record Daily Fish Thermoregulatory Behavior.

Photoperiod and temperature are two of the most powerful environmental cues that entrain circadian clocks. Being ectothermic, fish must keep their body temperature within a physiological range to optimize biological processes mainly applying behavioral strategies. Here, we developed a low-cost, automated system that allows to create a horizontal multiple-step thermal gradient and video record fish behavior for long-term periods.

An integrated computational and graphical approach for evaluating the geochemistry and health risks of nitrate-contaminated water for six age groups.

Nitrate contamination in drinking water poses significant health risks, particularly in rapidly urbanizing areas of developing countries. This study presents an integrated computational and graphical approach to evaluate the geochemistry and health risks of nitrate-contaminated water for six age groups in Southeast, Nigeria. The research employed a detailed methodology combining water nutrient pollution index (WNPI), nitrate pollution index (NPI), water pollution index (WPI), geochemical plotting techniques, stoichiometry, and health risk computations.

Discovery of xanthone-based nitric oxide donors targeting biofilm clearance.

Bacteria biofilm infection seriously challenges clinical drug therapy. Nitric oxide (NO) was reported to disperse biofilm, eliminate bacteria resistance and kill bacteria. In this study, on the basis of membrane targeting of α-mangostin (α-MG) and the dispersion effect of NO on bacteria biofilms, we designed and synthesized 30 NO donors that α-MG was conjugated with a nitrobenzene or a nitrate and other four representative reference derivatives.

HDAC3_VS_assistant: cheminformatics-driven discovery of histone deacetylase 3 inhibitors.

Histone deacetylase 3 (HDAC3) inhibitors keep significant therapeutic promise for treating oncological, neurodegenerative, and inflammatory diseases. In this work, we developed robust QSAR regression models for HDAC3 inhibitory activity and acute toxicity (LD, intravenous administration in mice). A total of 1751 compounds were curated for HDAC3 activity, and 15,068 for toxicity.