Challenges in Metabolite Biomarkers as Avenues of Diagnosis and Prognosis of Cancer.

Given the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels.

Potentiation of Tumor Hallmarks by the Loss of GULO, a Vitamin C Biosynthesis Gene in Humans.

Vitamin C plays a significant role in various physiological functions. Humans depend on external sources of vitamin C due to the loss of the L-gulono-γ-lactone oxidase (GULO) gene that contributes to the synthesis of vitamin C. During the evolutionary loss of the GULO gene, physical, chemical, and biological factors were different from the present environmental settings.

Precision in Pulmonary Embolism Diagnosis: Leveraging D-dimer Levels With Computed Tomography Pulmonary Angiography (CTPA) Insights.

Introduction Pulmonary embolism (PE) remains a critical condition requiring timely diagnosis and treatment. The use of D-dimer, a fibrin degradation product, as a biomarker, combined with computed tomography pulmonary angiography (CTPA), is a common practice in diagnosing PE. Aim This study aims to increase diagnostic accuracy for PE by relating the D-dimer levels to the findings on CTPA.

Enantioselective organocatalyzed one-pot synthesis of -phenyl thioether-tethered tetrasubstituted dihydropyrrole-3-carbaldehydes.

An efficient method for the asymmetric one-pot synthesis of -phenyl thioether-tethered tetrasubstituted chiral 4,5-dihydropyrrole-3-carbaldehydes have been developed using readily available benzothiazolium salts and α,β-unsaturated aldehydes as starting materials in the presence of the chiral organocatalyst ()-diphenylprolinol trimethylsilyl ether. The protocol afforded various functionally enantioenriched chiral tetrasubstituted 4,5-dihydropyrrole-3-carbaldehydes in high yields, with excellent enantio- and diastereoselectivity (≤90% yield, ≤98% ee, and >20 : 1 d.r.

Unusual Developmental Vascular Anomalies: Insights From a Chest Physician's Perspective.

This case report discusses three developmental vascular anomalies (DVAs) observed in adults and highlights the challenges related to the diagnosis and management. Even though detected at early ages, diagnostic difficulties are observed in the adult age due to the scarcity and diverse clinical features. These cases illustrate the necessity of a multidisciplinary approach involving clinicians and radiologists for precise and prompt diagnosis in adults, where misdiagnosis and delays in intervention are frequent.

Organocatalyzed Enantio- and Diastereoselective Formal Domino 1,3-Dipolar Cycloaddition/Rearrangement: Synthesis of Chiral Pyrrolo-thiazine-2-carbaldehydes.

An efficient approach for the synthesis of chiral pyrrolo[1,2-][1,4]thiazine-2-carbaldehydes is achieved via formal 1,3-dipolar cycloaddition/rearrangement reactions of benzothiazolium salt and α,β-unsaturated aldehydes, utilizing an asymmetric organocatalyst. This process results in the formation of fluorescent, highly enantioenriched chiral molecules with three contiguous stereogenic centers, one of which is a chiral quaternary center, with excellent yields and enantio- and diastereoselectivity. A computational study demonstrated the understanding of the reaction mechanism.

Understanding Cancer's Defense against Topoisomerase-Active Drugs: A Comprehensive Review.

In recent years, the emergence of cancer drug resistance has been one of the crucial tumor hallmarks that are supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters, and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.

Chalcogen bonding catalysis.

Catalysts play a major role in chemical synthesis, and catalysis is considered to be a green and economic process. Catalysis is dominated by covalent interactions between the catalyst and substrate. The design of non-covalent catalysts came into limelight only recently.

Secretion of acetylated amino acids by drug-induced cancer cells: perspectives on metabolic-epigenetic alterations.

The emerging understanding of the super-complex and heterogeneous nature of tumor is well supported by metabolic reprogramming, leading survival advantages. Metabolic reprogramming contributes to tumor responsiveness and resistance to various antitumor drugs. Among the numerous adaptations made by cancer cells in response to drug-induced perturbations, key metabolic alterations involving amino acids and acetylated derivatives of amino acids have received special attention.

Effect of β-sitosterol on insulin resistance & protein expression of insulin signalling molecules in quadriceps muscle of high fat diet-induced type-2 diabetic rats.

Changes in life style, such as high-calorie diet intake and lack of exercise, have increased the global prevalence of obesity and diabetes. The major pathophysiological event contributing to the development of type 2 diabetes mellitus is the target tissues to insulin action. Currently available drugs are unsuccessful for the treatment of type 2 diabetes due to their unwanted side effects.

CRISPR-Cas9 gene editing and human diseases.

CRISPR/Cas-9 mediated genome editing has recently emerged as a potential and innovative technology in therapeutic development and biomedical research. Several recent studies have been performed to understand gene modification techniques in obtaining effective ex vivo results. Generally, the disease targets for gene correction will be in specific organs, so understanding the complete potential of genomic treatment methods is essential.

The Identification of Potential Drugs for Dengue Hemorrhagic Fever: Network-Based Drug Reprofiling Study.

Background: Dengue fever can progress to dengue hemorrhagic fever (DHF), a more serious and occasionally fatal form of the disease. Indicators of serious disease arise about the time the fever begins to reduce (typically 3 to 7 days following symptom onset). There are currently no effective antivirals available.

Chemo- and Enantioselective Reduction of α-Keto Amides to α-Hydroxy Amides using Reusable CuO-Nanoparticles as Catalyst.

An efficient, commercially available, and reusable copper-oxide nanoparticle (CuO-NPs) and ()-(-)-DTBM SEGPHOS catalyzed chemo- and enantioselective reduction of α-keto amides to α-hydroxy amides has been developed. The scope of the reaction has been studied with various α-keto amides containing electron-donating and electron-withdrawing groups affording the enantiomerically enriched α-hydroxy amides in good yields with excellent enantioselectivity. The CuO-NPs catalyst has been recovered and reused up to four catalytic cycles without any significant change in particle size, reactivity, and enantioselectivity.

Binaphthyl-Stabilized Palladium Nanoparticle-Catalyzed Stereoselective Synthesis of 3-Arylidene-2-oxindoles via One-Pot Heck-like Carbocyclization/Nucleophilic Addition.

Stereoselective, one-pot synthesis of 3-arylidene-2-oxindoles has been accomplished via Heck-like carbocyclization/nucleophilic addition of -(2-iodophenyl)--methyl-3-phenylpropiolamide, phenylacetylene, and secondary amine using binaphthyl stabilized palladium nanoparticles (Pd-BNP) as a reusable catalyst. Less reactive aryl bromides generally provided a similar yield of 3-arylidene-2-oxindoles compared with more reactive aryl iodides. The Pd-BNP nanocatalyst has been recovered and recycled for five catalytic cycles with only an insignificant reduction in particle size, reactivity, and reaction yield.

A Conserved Histidine Residue Drives Extein Dependence in an Enhanced Atypically Split Intein.

Split intein-mediated protein trans-splicing (PTS) is widely applied in chemical biology and biotechnology to carry out traceless and specific protein ligation. However, the external residues immediately flanking the intein (exteins) can reduce the splicing rate, thereby limiting certain applications of PTS. Splicing by a recently developed intein with atypical split architecture ("Cat") exhibits a stark dependence on the sequence of its N-terminal extein residues.

Small molecule SJ572946 activates BAK to initiate apoptosis.

Poration of the outer mitochondrial membrane by the effector BCL-2 proteins BAK and BAX initiates apoptosis. BH3-only initiators BID and BIM trigger conformational changes in BAK and BAX transforming them from globular dormant proteins to oligomers of the apoptotic pores. Small molecules that can directly activate effectors are being sought for applications in cancer treatment.

Cu-Catalyzed and iodine mediated synthesis of thioaurones C-S bond generation using xanthate as a sulfur surrogate.

An efficient method for synthesizing thioaurones has been developed using xanthate as an odorless sulfur surrogate. This reaction's key success lies in the use of iodine as a reagent, which promotes the α-iodination followed by cyclization of saturated ketones. This methodology has also been demonstrated with less reactive 2'-bromochalcones in good yield.

Halogen Bond-Activated Visible-Light-Mediated Regioselective C-H Arylation of 2-Phenylimidazo-[1,2-]pyridines.

An efficient method for transition metal-free halogen bond-assisted regioselective C-H arylation of 2-phenylimidazo-[1,2-]pyridines under visible-light condition has been developed. The halogen bond between an aryl halide and base KOBu initiates an electron transfer process and generates an aryl radical, which catalyzes its coupling with 2-phenylimidazo-[1,2-]pyridines to give arylated products in good yield. Several control experiments, density functional theory calculations, and ultraviolet-visible analysis indicate the presence of a halogen bond between an aryl halide and KOBu.

Transition Metal-Free Iodine-Catalyzed Denitrative C-S Cross-Coupling: An Atypical Route to Access Thiochromane Derivatives.

An iodine-catalyzed denitrative C-S cross-coupling reaction has been developed to attain thiochromanones from 2'-nitrochalcones and xanthate. The strategy was extended for a three-component synthesis of thiochromenes via intermolecular C-S cross-coupling followed by aldol reaction. The reaction proceeds via activation of the keto group of chalcone through a halogen bond complex with iodine/denitrative C-S bond formation with xanthate/sulfa-Michael addition to chalcones.

Segmentation of Optic Disc and Cup Using Modified Recurrent Neural Network.

Glaucoma is one of the leading factors of vision loss, where the people tends to lose their vision quickly. The examination of cup-to-disc ratio is considered essential in diagnosing glaucoma. It is hence regarded that the segmentation of optic disc and cup is useful in finding the ratio.

Protein-protein and protein-lipid interactions of pore-forming BCL-2 family proteins in apoptosis initiation.

Apoptosis is a common cell death program that is important in human health and disease. Signaling in apoptosis is largely driven through protein-protein interactions. The BCL-2 family proteins function in protein-protein interactions as key regulators of mitochondrial poration, the process that initiates apoptosis through the release of cytochrome c, which activates the apoptotic caspase cascade leading to cellular demolition.

Iodine-Promoted Controlled and Selective Oxidation of (Aryl)(Heteroaryl)Methanes.

The development of direct and controlled oxidation of C-H bonds is of great importance. Herein, an iodine-catalyzed controlled oxidation of (aryl)(heteroaryl)methanes to (aryl)(heteroaryl)methanols is disclosed under metal-free reaction conditions. A catalytic system comprised of iodine/silyl chloride with HI as an additive in the presence of dimethyl sulfoxide selectively oxidizes the C-H bonds without being overoxidized to corresponding ketones.

KOBu-Promoted Halogen-Bond-Assisted Intramolecular C-S Cross-Coupling of -Iodothioanilides for the Synthesis of 2-Substituted Benzothiazoles.

An efficacious and mild KOBu-promoted intramolecular C-S cross-coupling of -iodothioanilides in conjunction with a catalytic quantity of phenanthroline as an additive has been described for the convenient synthesis of 2-substituted benzothiazoles. The methodology is suitable for attaining a wide variety of 2-alkyl- and 2-aryl-substituted benzothiazoles. Single-crystal XRD, DFT calculations, NMR, and UV studies suggest that halogen bonds between the units of -iodothioanilides may assist in the electron transfer process.

Copper-catalyzed domino synthesis of multi-substituted benzo[b]thiophene through radical cyclization using xanthate as a sulfur surrogate.

The Cu-catalyzed domino synthesis of multi-substituted benzo[b]thiophene through radical cyclization of 2-iodophenyl ketones was developed using xanthate as a sulfur surrogate. This method was extended to obtain tetracyclic Lupinalbin analogues through double C-S/C-O bond formation by changing the substituents. The products were converted to a HTI photoswitch, benzothiophene-fused flavone.

Visible Light Mediated Photocatalyst Free C-S Cross Coupling: Domino Synthesis of Thiochromane Derivatives via Photoinduced Electron Transfer.

An efficient visible light mediated photocatalyst free C-S cross-coupling reaction has been developed for the synthesis of thiochromane derivatives through photoinduced electron transfer (PET). This methodology was further utilized for the synthesis of thiochroman-4-ol through intermolecular three-component cross-coupling reaction. The reaction proceeds via C-S bond formation through EDA complex/thioester cleavage/inter-or intramolecular -Michael addition followed by aldol reaction sequence.