Diketopiperazine/piperidine alkaloid as a potential broad-spectrum coronaviral entry inhibitor identified by supercomputer-based virtual screening from a large natural product-based library.

The COVID-19 pandemic has underscored the urgent need for antiviral agents capable of targeting a broad range of coronaviruses, including emerging variants of SARS-CoV-2. While vaccines have been pivotal, the search for drugs that can prevent viral entry into host cells remains crucial, especially against evolving viral forms and other coronaviruses. In this study, we investigated natural products as a source of antiviral agents, focusing on their potential to block the spike protein's receptor-binding domain (RBD).

The challenge of integrating a diagnosis of malnutrition in the practical application of nutrition care in the intensive care unit.

Evidence of poor nutrition status in a patient present on admission to the intensive care unit is associated with worse clinical outcomes than that for a well-nourished patient who becomes critically ill. Diagnosing malnutrition in this setting is fraught with difficulty, though, because elements of nutrition history are hard to obtain, the interpretation of anthropometric parameters is influenced by the disease process and interventions of critical care and the subjectivity of traditional assessment tools lacks precision. Determining the severity of disease drives the initial management and sets priorities in the derivation of the nutrition plan, focusing on strategies that promote survival.

Systemic biological mechanisms underpin poor post-discharge growth among severely wasted children with HIV.

In sub-Saharan Africa, children with severe malnutrition (SM) and HIV have substantially worse outcomes than children with SM alone, facing higher mortality risk and impaired nutritional recovery post-hospitalisation. Biological mechanisms underpinning this risk remain incompletely understood. This case-control study nested within the CHAIN cohort in Kenya, Uganda, Malawi, and Burkina Faso examined effect of HIV on six months post-discharge growth among children with SM and those at risk of malnutrition, assessed proteomic signatures associated with HIV in these children, and investigated how these systemic processes impact post-discharge growth in children with SM.

Deciphering the complexity of the chemicals in food packaging materials using molecular networks.

Chemicals from packaging materials might be transferred into food resulting in consumer exposure. Identifying these migrated chemicals is highly challenging and crucial to perform their safety assessment, usually starting by the understanding of the chemical composition of the packaging material itself. This study explores the use of the Molecular Networking (MN) approach to support identification of the extracted chemicals.

Jejunal Gastrointestinal Stromal Tumor Presenting as Hemorrhagic Shock.

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal (GI) tract. Intermittent GI bleeding is the most common manifestation. Massive GI bleeding leading to syncopal episodes and hemorrhagic shock is a rare presentation of these tumors.

Managing Micronutrient Deficiencies in High-Risk Patients: No Small Feat!

Purpose Of Review: Micronutrients are vital dietary components for growth and development. Adequate intake of vitamins and minerals through diet is crucial for proper biomolecular and cellular functioning. Many developed countries supplement foods and micronutrient deficiencies are less common.

Does Ileus Represent the Forgotten End Organ Failure in Critical Illness?

Purpose Of Review: This review evaluates the current literature on ileus, impaired gastrointestinal transit (IGT), and acute gastrointestinal injury (AGI) and its impact on multiple organ dysfunction syndrome.

Recent Findings: Ileus is often under recognized in critically ill patients and is associated with significant morbidity and is potentially a marker of disease severity as seen in other organs like kidneys (ATN).

Fat digestion and absorption: Normal physiology and pathophysiology of malabsorption, including diagnostic testing.

Fat digestion and absorption play crucial roles in maintaining energy homeostasis and supporting essential physiological functions. The initial stage of fat digestion occurs in the stomach, where gastric lipase begins the hydrolysis of triglycerides. However, most fat digestion takes place in the small intestine via pancreatic enzymes and bile salts.

Enhancing the notification system for surveillance of infectious diseases in Qatar during the FIFA World Cup 2022: project overview.

Background: In 2022, the Surveillance Department of the Ministry of Public Health in Qatar adopted an integrated project called the Notification Enhancement Project (NEP) to enhance the infectious disease notification system. Efficient surveillance and notification promote early alerts and allow immediate interference in reducing morbidity and mortality from outbreaks. The project was designed to improve the knowledge, attitudes, practices, and notification processes of healthcare workers in Qatar by increasing their reporting rates.

Distinct transcriptomic signatures define febrile malaria depending on initial infective states, asymptomatic or uninfected.

Background: Cumulative malaria parasite exposure in endemic regions often results in the acquisition of partial immunity and asymptomatic infections. There is limited information on how host-parasite interactions mediate the maintenance of chronic symptomless infections that sustain malaria transmission.

Methods: Here, we determined the gene expression profiles of the parasite population and the corresponding host peripheral blood mononuclear cells (PBMCs) from 21 children (< 15 years).

Identification of Antagonistic Action of Pyrrolizidine Alkaloids in Muscarinic Acetylcholine Receptor M1 by Computational Target Prediction Analysis.

Pyrrolizidine alkaloids (PAs) are one of the largest distributed classes of toxins in nature. They have a wide range of toxicity, such as hepatotoxicity, pulmonary toxicity, neuronal toxicity, and carcinogenesis. Yet, biological targets responsible for these effects are not well addressed.

Investigating the Cytotoxicity of Ru(II) Polypyridyl Complexes by Changing the Electronic Structure of Salicylaldehyde Ligands.

A novel class of Ru(II)-based polypyridyl complexes with an auxiliary salicylaldehyde ligand [Ru(phen)(X-Sal)]BF {X: H (), 5-Cl (), 5-Br (), 3,5-Cl (), 3,5-Br (), 3-Br,5-Cl (), 3,5-I (), 5-NO (), 5-Me (), 4-Me (), 4-OMe (), and 4-DEA (), has been synthesized and characterized by elemental analysis, FT-IR, and H/C NMR spectroscopy. The molecular structure of , , , , and was determined by single-crystal X-ray diffraction analysis which revealed structural similarities. DFT and TD-DFT calculations showed that they also possess similar electronic structures.

The importance of providing dietary fiber in medical and surgical critical care.

The early provision of soluble/insoluble fiber to the patient who is critically ill has been controversial in the past. Especially in the setting of hemodynamic instability, dysmotility, or impaired gastrointestinal transit, fear of inspissation of formula with precipitation of nonocclusive mesenteric ischemia (NOMI)/nonocclusive bowel necrosis (NOBN) limited its utilization by medical and surgical intensivists. The incidence of NOMI/NOBN has been estimated at 0.

The Effect of Plastic-Related Compounds on Transcriptome-Wide Gene Expression on CYP2C19-Overexpressing HepG2 Cells.

In recent years, plastic and especially microplastic in the oceans have caused huge problems to marine flora and fauna. Recently, such particles have also been detected in blood, breast milk, and placenta, underlining their ability to enter the human body, presumably via the food chain and other yet-unknown mechanisms. In addition, plastic contains plasticizers, antioxidants, or lubricants, whose impact on human health is also under investigation.

Modes of Action of a Novel c-MYC Inhibiting 1,2,4-Oxadiazole Derivative in Leukemia and Breast Cancer Cells.

The oncogene regulates multiple cellular activities and is a potent driver of many highly aggressive human cancers, such as leukemia and triple-negative breast cancer. The oxadiazole class of compounds has gained increasing interest for its anticancer activities. The aim of this study was to investigate the molecular modes of action of a 1,2,4-oxadiazole derivative (ZINC15675948) as a c-MYC inhibitor.

Two palladium (II) complexes derived from halogen-substituted Schiff bases and 2-picolylamine induce parthanatos-type cell death in sensitive and multi-drug resistant CCRF-CEM leukemia cells.

The use of cisplatin and its derivatives in cancer treatment triggered the interest in metal-containing complexes as potential novel anticancer agents. Palladium (II)-based complexes have been synthesized in recent years with promising antitumor activity. Previously, we described the synthesis and cytotoxicity of palladium (II) complexes containing halogen-substituted Schiff bases and 2-picolylamine.

In Silico and In Vitro Identification of P-Glycoprotein Inhibitors from a Library of 375 Phytochemicals.

Cancer therapy with clinically established anticancer drugs is frequently hampered by the development of drug resistance of tumors and severe side effects in normal organs and tissues. The demand for powerful, but less toxic, drugs is high. Phytochemicals represent an important reservoir for drug development and frequently exert less toxicity than synthetic drugs.

Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma.

The majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model.

Juice Shows Anti-Fungal Efficacy in Experimental Oral Candidiasis in Immunosuppressed Rats in Relation to Its Chemical Profile.

(Syn. ) () is used in the rural Egypt to treat oral ulcers in newborn children. The current study aimed to discover new natural products suitable for treating candidiasis disease with minimal side effects.

Synthesis and Bioactivity of Isoflavones from and Some Non-Natural Analogues.

Ficucaricone D () and its 4'-demethyl congener are isoflavones isolated from fruits of that share a 5,7-dimethoxy-6-prenyl-substituted A-ring. Both natural products were, for the first time, obtained by chemical synthesis in six steps, starting from 2,4,6-trihydroxyacetophenone. Key steps are a microwave-promoted tandem sequence of Claisen- and Cope-rearrangements to install the 6-prenyl substituent and a Suzuki-Miyaura cross coupling for installing the B-ring.