Epidermal growth factor receptor mutations in breast Cancer: Therapeutic challenges and way forward.

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that is upregulated in aggressive triple-negative breast cancer (TNBC). Ligands such as EGF, TGF-α, epigen, and amphiregulin activate the auto-phosphorylation activity of tyrosine residues on EGFR, which regulates the growth, proliferation, adhesion, migration, and survival of cancer cells. Our prior studies depicted that inhibition of EGFR modulates the chemosensitivity in breast cancer stem cells and, thus, serves as a potent therapeutic target in breast cancer.

BINAP-CuH-catalysed enantioselective allylation using alkoxyallenes to access 1,2-,-diols.

Herein, we present an economical method for highly enantioselective and diastereoselective Cu-BINAP-catalysed reductive coupling of alkoxyallenes with a range of electronically and structurally diverse ketones to afford 1,2-,-diols, using PMHS as the hydride source. This reductive coupling has also been efficiently employed in the enantioselective desymmetrization of prochiral cyclic ketones harboring quaternary centres, in high yields with exclusive diastereoselectivity. Density Functional Theory (DFT) calculations are used to elucidate that the reaction is facilitated by a kinetically favourable "open" -enolate copper-alkoxyallene conformer, occurring at a lower Gibbs free energy barrier (by 3.

Design and application of intramolecular arylogous nitroaldol condensation to access 2-aryl-benzofuran and -indole derivatives and formal synthesis of saprisartan.

This study presents the design and application of intramolecular arylogous nitroaldol (Henry) condensation. A transition metal-free, base-mediated reaction of -heteroatom-substituted aryl aldehydes/ketones and 2-nitrobenzyl (pseudo)halides has been developed to access a wide range of 2-(2-nitroaryl)benzofuran/2-(2-nitroaryl)indole derivatives in high yields. The reaction appears to proceed through -/-benzylation and intramolecular arylogous nitroaldol condensation.

Severity prediction markers in dengue: a prospective cohort study using machine learning approach.

Background: Dengue virus causes illnesses with or without warning indicators for severe complications. There are no clear prognostic signs linked to the disease outcomes.

Methods: Clinical and laboratory parameters among 102 adult including 17 severe dengue (SD), 33 with warning and 52 without warning signs during early and critical phases were analysed by statistical and machine learning (ML) models.

NHC-Catalyzed Umpolung Driven Intramolecular Cyclizations for the Generation of 3,4-Cycloheptanone Annulated Tetracyclic Indole Derivatives.

In this Letter, we disclose the development and exploitation of umpolung reactivity of N-heterocyclic carbene (NHC) organocatalysts in generating tetracyclic indole derivatives with the introduction of a cycloheptane ring forming event. The NHC-catalyzed intramolecular vinylogous Stetter, Stetter, benzoin, and formal cross-dehydrogenative coupling transformations have been executed, enabling the construction of 3,4-cycloheptannulated indole derivatives in good to excellent yields. The developed protocols utilize an inexpensive catalyst and feature operational simplicity, atom economy, gram-scale syntheses, and postsynthetic availability.

Virtual screening, molecular dynamics simulations, and in vitro validation of EGFR inhibitors as breast cancer therapeutics.

A high abundance of Epidermal Growth Factor Receptor (EGFR) in malignant cells makes them a prospective therapeutic target for basal breast tumors. Although EGFR inhibitors are in development as anticancer therapeutics, there exists limitations due to the dose-limiting cytotoxicity that limits their clinical utilization, thereby necessitating the advancement of effective inhibitors. In the present study, we have developed common pharmacophore hypotheses using 30 known EGFR inhibitors.

Total Synthesis of an Immunosuppressive C Macrocyclic Terpenoid Produced by Terpene Synthase (2).

Macrocyclic natural products, particularly those with no functionalities except unsaturation, are recognized for their therapeutic potential but are notoriously challenging to synthesize. In this study, we report the first total synthesis of an unconventional 18-membered, C macrocyclic terpenoid, which has demonstrated substantial immunosuppressive activity. This synthesis was achieved through strategic modifications and innovative reaction engineering, utilizing α-terpineol and geraniol as starting materials, highlighting a novel approach in macrocyclic terpenoid synthesis.

Visible-Light-Promoted Iron(II)/Lewis Base Catalysis for the Alkylation of Morita-Baylis-Hillman Acetates Using Carboxylic Acids.

A novel photoinduced Fe(OTf)/2,4,6-collidine-catalyzed alkylation of Morita-Baylis-Hillman (MBH) acetates using carboxylic acids in a regio- and stereoselective manner is reported. This method demonstrates a broad scope, encompassing various carboxylic acids and MBH acetates, including drugs and bioactive molecules, to synthesize densely functionalized cinnamates and acrylates. The reactions are performed in the green solvent dimethyl carbonate under oxidant-free conditions.

Acid-Mediated Intramolecular Cyclizations of (-Aryl)-acetylenic Sulfonamides: Synthesis of Fused and Spirocyclic Sultams.

Herein, we report acid-mediated divergent annulations of (-aryl)-alkynyl sulfonamides. The substituent at the position of the -aryl group determines two diverse reaction paths, leading to the selective assembly of benzo-fused sultams and spirocyclic sultams. This strategy provides a series of benzo/spiro-sultams with wide functional group compatibility and good to excellent yields under mild reaction conditions.

Ag(I)-catalyzed diastereoselective oxidative cyclopropanation of prochiral alkyne-tethered 1,3-dicarbonitriles.

Herein, we developed a highly diastereoselective silver-catalyzed intramolecular cyclopropanation of prochiral alkyne-tethered 1,3-dicarbonitriles using perchloric acid as an effective oxidizing agent. This method facilitates the construction of densely functionalized complex [6.6.

Increased shedding of PECAM-1 associated with elevated serum MMP-14 levels as new blood indicators of dengue disease manifestation.

Objectives: Host factors that regulate plasma leakage during severe dengue (SD) are under investigation. While PECAM-1 and MMP-14 have been reported to regulate vascular integrity, their role in dengue pathogenesis remains unexplored. This study aims to assess the association of soluble PECAM-1 and MMP-14 with dengue severity symptoms.

Cascade Oxypalladation/1,3-Palladium Shift to Access Cyclopentene-Fused Isocoumarins.

Fused isocoumarins are frequently found in several natural products and pharmaceuticals. Herein, a cascade annulation of 2-alkynylbenzoate-tethered cyclic 1,3-diones via sequential -oxypalladation, carbonyl insertion, 1,3-Pd shift, and β-hydride elimination is reported. This method provides efficient access to highly diastereoselective tetracyclic cyclopentene-fused isocoumarins containing two contiguous quaternary stereocenters.

3D Porous Polymer Scaffold-Conjugated KGF-Mimetic Peptide Promotes Functional Skin Regeneration in Chronic Diabetic Wounds.

The re-epithelialization process gets severely dysregulated in chronic nonhealing diabetic foot ulcers/wounds. Keratinocyte growth factor (KGF or FGF-7) is the major modulator of the re-epithelialization process, which regulates the physiological phenotypes of cutaneous keratinocytes. The existing therapeutic strategies of growth factor administration have several limitations.

Nickel-Catalyzed Alkene Isomerization to Access Bench-Stable Enamines and Their [3 + 2] Annulation.

Enamines are difficult to prepare on the bench due to their instability, which results in side reactions, decompositions, poor yields, etc. Herein, we developed a simple and effective method for making bench-stable enamines using a very low amount of nickel catalyst loading. The deuterium exchange, competitive reaction, and radical clock experiment have all been found to favor the ionic mechanism of this alkene isomerization.

Understanding COVID-19 outcome: Exploring the prognostic value of soluble biomarkers indicative of endothelial impairment.

Host proteins released by the activated endothelial cells during SARS-CoV-2 infection are implicated to be involved in coagulation and endothelial dysfunction. However, the underlying mechanism that governs the vascular dysfunction and disease severity in COVID-19 remains obscure. The study evaluated the serum levels of Bradykinin, Kallikrein, SERPIN A, and IL-18 in COVID-19 (N-42 with 20 moderate and 22 severe) patients compared to healthy controls (HC: N-10) using ELISA at the day of admission (DOA) and day 7 post-admission.

Glucosyltriazole amphiphile treatment attenuates breast cancer by modulating the AMPK signaling.

Breast cancer is the second most frequent cancer among women. Out of various subtypes, triple-negative breast cancers (TNBCs) account for 15% of breast cancers and exhibit more aggressive characteristics as well as a worse prognosis due to their proclivity for metastatic progression and limited therapeutic strategies. It has been demonstrated that AMP-activated protein kinase (AMPK) has context-specific protumorigenic implications in breast cancer cells.

Access to N-Fused Quinazolinones by Radical-Promoted Cascade Annulations of Alkenyl -Cyanamides with Aromatic Aldehydes.

A cascade radical cyclization of alkenyl -cyanamides with aromatic aldehydes has been achieved for an expeditious synthesis of keto-methylated dihydropyrrolo-quinazolinones. Benzoyl radicals, generated from aryl aldehydes in the presence of di--butyl peroxide (DTBP), promoted the domino annulations leading to distinctive functionalized quinazolinones in good yields. In addition, the robustness of the present protocol is validated by employing heterocyclic and natural product-based aldehydes.

Purification of Waste-Generated Biogas Mixtures Using Covalent Organic Framework's High CO Selectivity.

Development of crystalline porous materials for selective CO adsorption and storage is in high demand to boost the carbon capture and storage (CCS) technology. In this regard, we have developed a β-keto enamine-based covalent organic framework () via the Schiff base polycondensation technique. The as-synthesized exhibited excellent thermal and chemical stability along with a very high surface area (1258 m g) and a high CO adsorption capacity (3.

Deoxyfluorinated amidation and esterification of carboxylic acid by pyridinesulfonyl fluoride.

Amide bond synthesis is one of the most used reactions in medicinal chemistry. We report an amide bond formation reaction through deoxyfluorinated carboxylic acids under mild conditions using 2-pyridinesulfonyl fluoride. The reaction procedure has been used in a one-pot synthesis of amides and esters generation of acyl fluoride.

Bioengineered MSC transdifferentiated keratinocyte-like cell-derived organoid potentiates skin regeneration through ERK1/2 and STAT3 signaling in diabetic wound.

Skin regeneration is severely compromised in diabetic foot ulcers. Allogeneic mesenchymal stem cell (MSC) transplantation is limited due to the poor engraftment, mitogenic, and differentiation potential in the harsh wound microenvironment. Thus, to improve the efficacy of cell therapy, the chemokine receptor Cxcr2 was overexpressed in MSCs (MSC).

Epidermal growth factor receptor inhibition potentiates chemotherapeutics-mediated sensitization of metastatic breast cancer stem cells.

Background: Metastasis has been a cause of the poor prognosis and cancer relapse of triple-negative breast cancer (TNBC) patients. The metastatic nature of TNBC is contributed by the breast cancer stem cells (CSCs) which have been implicated in tumorigenesis. Higher expression of epidermal growth factor receptor (EGFR) in breast CSCs has been used as a molecular target for breast cancer therapeutics.

Organocatalytic enantioselective desymmetrization of enal-tethered cyclohexane-1,3-diones.

Organocatalytic asymmetric desymmetrization of prochiral cyclohexane-1,3-diones has been demonstrated through the merging of iminium and enamine activation. The tandem annulation reaction proceeds through a sequential oxa-Michael addition/intramolecular aldol reaction/[1,3]-amino oxetane rearrangement pathway. Mechanistic study using an O-water experiment suggests oxetane rearrangement instead of direct dehydration.

Modulating cultivation regimes of Messastrum gracile SVMIICT7 for biomass productivity integrated with resource recovery via hydrothermal liquefaction.

The present study was designed to assess Messastrum gracile SVMIICT7 potential in treating dairy wastewater (autoclaved (ADWW) and raw (DWW)) with relation to nutrient removal, in-vivo Chl-a-based biomass, and bio-oil synthesis. Chlorophyll a fluorescence kinetics revealed improved photochemical efficiency (0.639, Fv/Fm) in M.