Building Metabolically Stable and Potent Anti-HIV Thioether-Lipid Analogues of Tenofovir Exalidex: A thorough Pharmacological Analysis.

Inherently limited by poor bioavailability, antiviral agent tenofovir (TFV) is administered to people living with HIV in prodrug form. However, current prodrugs are prematurely metabolized, compromising access to HIV-infected cells and inducing toxicity. Inspired by lipid conjugate TFV exalidex (TXL), we recently disclosed TXL analogs with potent activity and robust hepatic stability in vitro, as well as attractive oral PK profiles in vivo.

Characterization of a CXCR4 antagonist TIQ-15 with dual tropic HIV entry inhibition properties.

The chemokine co-receptors CXCR4 and CCR5 mediate HIV entry and signal transduction necessary for viral infection. However, to date only the CCR5 antagonist maraviroc is approved for treating HIV-1 infection. Given that approximately 50% of late-stage HIV patients also develop CXCR4-tropic virus, clinical anti-HIV CXCR4 antagonists are needed.

Development of high-yielding white maize hybrids with better -making quality compared to traditionally used local landraces.

Introduction: The present research focuses on the chapatti making quality of high-yielding white maize hybrids compared to available low-yielding local yellow and white landraces in India.

Materials And Methods: In this study, the top nine superior hybrids were selected for testing the physical properties of the maize kernels, proximate composition of flours and , physical parameters of , textural properties, sensory evaluation of and pasting properties of maize flour.

Results And Discussion: The results revealed the superiority of white maize hybrids (WMH), , WHM 1, WHM 2, and WHM 8 over the local yellow and white landraces for most of the parameters studied.

Operational outcomes of propofol sedation versus fentanyl, midazolam and diphenhydramine sedation for endoscopies and colonoscopies at an academic medical center.

Background: On July 1st, 2021, the University of Colorado Hospital (UCH) implemented new sedation protocols in the luminal gastrointestinal (GI) suite. GI proceduralist supervised, Nurse Administered Sedation with fentanyl, midazolam, and diphenhydramine (NAS) sedation was transitioned to Monitored Anesthesia Care with propofol under physician anesthesiologist supervision (MAC).

Objective: To determine if there are statistically significant reductions in Sedation-Start to Scope-In time (SSSI) when using Monitored Anesthesia Care with propofol (MAC) versus Nurse Administered Sedation with fentanyl, midazolam, and diphenhydramine (NAS).

Development of a Dihydroquinoline-Pyrazoline GluN2C/2D-Selective Negative Allosteric Modulator of the -Methyl-d-aspartate Receptor.

Subunit-selective inhibition of -methyl-d-aspartate receptors (NMDARs) is a promising therapeutic strategy for several neurological disorders, including epilepsy, Alzheimer's and Parkinson's disease, depression, and acute brain injury. We previously described the dihydroquinoline-pyrazoline (DQP) analogue () as a potent NMDAR negative allosteric modulator with selectivity for GluN2C/D over GluN2A/B. However, moderate (<100-fold) subunit selectivity, inadequate cell-membrane permeability, and poor brain penetration complicated the use of as an probe.

Effect of extrusion processing on techno-functional properties, textural properties, antioxidant activities, in vitro nutrient digestibility and glycemic index of sorghum-chickpea-based extruded snacks.

Physico-chemical, textural, functional, and nutritional properties of the twin screw extruded whole sorghum-chickpea (8:2) snacks was investigated using in vitro procedures. The extruded snacks were analyzed for the effect of variations in extruded conditions on their properties: barrel BT (BT) (130-170°C) and feed moisture (FM) (14%-18%), keeping screw speed constant (400 rpm). The results revealed that specific mechanical energy (SME) decreased (74.

Discovery of 5'-Substituted 5-Fluoro-2'-deoxyuridine Monophosphate Analogs: A Novel Class of Thymidylate Synthase Inhibitors.

5-Fluorouracil and 5-fluorouracil-based prodrugs have been used clinically for decades to treat cancer. Their anticancer effects are most prominently ascribed to inhibition of thymidylate synthase (TS) by metabolite 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). However, 5-fluorouracil and FdUMP are subject to numerous unfavorable metabolic events that can drive undesired systemic toxicity.

Neurotherapeutic Potential of Water-Soluble pH-Responsive Prodrugs of EIDD-036 in Traumatic Brain Injury.

The C-20 oxime of progesterone, EIDD-036 (), demonstrates neuroprotection and improved outcomes in animal models of traumatic brain injury (TBI). However, suffers from poor solubility, which renders it unsuitable for rapid administration. Previous prodrugs of aimed at improving solubility by incorporating enzymatically labile amino acid and phosphate ester promoieties.

Expanding the toolbox of metabolically stable lipid prodrug strategies.

Nucleoside- and nucleotide-based therapeutics are indispensable treatment options for patients suffering from malignant and viral diseases. These agents are most commonly administered to patients as prodrugs to maximize bioavailability and efficacy. While the literature provides a practical prodrug playbook to facilitate the delivery of nucleoside and nucleotide therapeutics, small context-dependent amendments to these popular prodrug strategies can drive dramatic improvements in pharmacokinetic (PK) profiles.

Modulation in Techno-Functional, Textural Properties, In Vitro Starch Digestibility and Macromolecular-Structural Interactions of Pasta with Potato ( L.).

The replacement of semolina with potato flour (PF) and potato mash (PM) at different levels was assessed for its effects on pasta quality. The results showed that the addition of PF and PM increased the pasting viscosity of the blends; in addition, PF enhanced the functional properties, while PM reduced them. The minimum cooking time decreased with PF and PM, while the PF pasta exhibited a higher cooking loss (5.

Cereal bar functionalised with non-conventional alfalfa and dhaincha protein isolates: quality characteristics, nutritional composition and antioxidant activity.

The utilization of conventional protein sources like gluten, soy, dairy proteins, and nuts in the development of protein-enriched cereal bars presents a challenge for their consumption by the population suffering from celiac and other food protein allergies. In the present investigation, protein-rich cereal bars were developed using non-conventional protein isolates (alfalfa and dhiancha (API & DPI) and were evaluated for their quality attributes, nutritional composition, and bioactive potential. The incorporation of protein isolates increased the weight, density, and non-enzymatic browning and decreased the water activity in the bars.

Effect of extrusion processing on techno-functional, textural and bioactive properties of whole-grain corn flour-based breakfast cereals sweetened with honey.

The present study investigated the effect of honey and extrusion processing parameters on techno-functional and bioactive properties of whole-grain corn flour breakfast cereals. The central composite rotatable design (CCRD) was used to plan the experiments using feed moisture (FM), extrusion temperature (ET), and honey level as process variables and sectional expansion ratio (SER), bulk density (BD), water absorption index (WAI), water solubility index (WSI), and textural hardness as response variables. The feed containing honey and whole-grain corn flour was extruded through a twin-screw extruder according to CCRD.

The Toxoplasma glucan phosphatase TgLaforin utilizes a distinct functional mechanism that can be exploited by therapeutic inhibitors.

Toxoplasma gondii is an intracellular parasite that generates amylopectin granules (AGs), a polysaccharide associated with bradyzoites that define chronic T. gondii infection. AGs are postulated to act as an essential energy storage molecule that enable bradyzoite persistence, transmission, and reactivation.

Assessment of physicochemical, rheological, and thermal properties of Indian rice cultivars: Implications on the extrusion characteristics.

The implications of physicochemical, rheological, and thermal properties of seven eminent Indian rice cultivars (PR 114, 121, 122, 123, 124, 126, and 127) on the extrusion behavior and physico-functionalities of the extrudates were investigated. The amylose and amylopectin content of the cultivars ranged between 12.72 to 28.

Crystal structure and vibrational spectra of (2-isobutyrylamidophenyl)amine: a redox noninnocent ligand.

The molecular structure of (2-isobutyrylamidophenyl)amine (HL) has been determined from single-crystal X-ray diffraction data. The crystal packing of HL is governed by the N-H···O and C-H···O hydrogen-bonding and C-H···π stacking interactions between the vicinal molecules. The intermolecular interactions in the crystal structure of HL have been also examined via Hirshfeld surface analysis and fingerprint plots.

ω-Functionalized Lipid Prodrugs of HIV NtRTI Tenofovir with Enhanced Pharmacokinetic Properties.

Tenofovir (TFV) is the cornerstone nucleotide reverse transcriptase inhibitor (NtRTI) in many combination antiretroviral therapies prescribed to patients living with HIV/AIDS. Due to poor cell permeability and oral bioavailability, TFV is administered as one of two FDA-approved prodrugs, both of which metabolize prematurely in the liver and/or plasma. This premature prodrug processing depletes significant fractions of each oral dose and causes toxicity in kidney, bone, and liver with chronic administration.

Anti-nutrient & bioactive profile, in vitro nutrient digestibility, techno-functionality, molecular and structural interactions of foxtail millet (Setaria italica L.) as influenced by biological processing techniques.

The present investigation aimed at assessing the impact of biological processing techniques on bio-and techno-functional characteristics of foxtail millet (Setaria italica L.). Grains were exposed to soaking, germination, fermentation and combination of aforesaid treatments and significant variation (p < 0.

Cooperative Kinetics of the Glucan Phosphatase Starch Excess4.

Glucan phosphatases are members of a functionally diverse family of dual-specificity phosphatase (DSP) enzymes. The plant glucan phosphatase Starch Excess4 (SEX4) binds and dephosphorylates glucans, contributing to processive starch degradation in the chloroplast at night. Little is known about the complex kinetics of SEX4 when acting on its complex physiologically relevant glucan substrate.

Dynamics of Germination Behaviour, Protein Secondary Structure, Technofunctional Properties, Antinutrients, Antioxidant Capacity and Mineral Elements in Germinated Dhaincha.

Research Background: Dhaincha () is a forage legume primarily used for green manuring and animal feed. Good nutritional profile of dhaincha makes it a potential alternative legume in human nutrition. However, the presence of high amount of antinutrients poses a problem in its utilisation for food applications.

Generation and characterization of a laforin nanobody inhibitor.

Objectives: Mutations in the gene encoding the glycogen phosphatase laforin result in the fatal childhood dementia Lafora disease (LD). A cellular hallmark of LD is cytoplasmic, hyper-phosphorylated, glycogen-like aggregates called Lafora bodies (LBs) that form in nearly all tissues and drive disease progression. Additional tools are needed to define the cellular function of laforin, understand the pathological role of laforin in LD, and determine the role of glycogen phosphate in glycogen metabolism.

Enhancement of Digestibility of Nutrients (In vitro), Antioxidant Potential and Functional Attributes of Wheat Flour Through Grain Germination.

Wheat grains were germinated at different time (12, 24, 36, and 48 h) and temperature (25, 30, and 35°C) to enhance the functionality of resultant flour. Results revealed that an increase in germination time and temperature enhanced the in vitro digestibility of starch (10.35-42.

The association of circulating amylin with β-amyloid in familial Alzheimer's disease.

Introduction: This study assessed the hypothesis that circulating human amylin (amyloid-forming) cross-seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods: Evidence of amylin-AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non-APP/PS1 rats.

Ferric Heme Superoxide Reductive Transformations to Ferric Heme (Hydro)Peroxide Species: Spectroscopic Characterization and Thermodynamic Implications for H-Atom Transfer (HAT).

A new end-on low-spin ferric heme peroxide, [(P )Fe -(O )] (P -P), and subsequently formed hydroperoxide species, [(P )Fe -(OOH)] (P -HP) are generated utilizing the iron-porphyrinate P with its tethered axial base imidazolyl group. Measured thermodynamic parameters, the ferric heme superoxide [(P )Fe -(O )] (P -S) reduction potential (E°') and the P -HP pK value, lead to the finding of the OO-H bond-dissociation free energy (BDFE) of P -HP as 69.5 kcal mol using a thermodynamic square scheme and Bordwell relationship.