Metabolic Syndrome: Updates on Pathophysiology and Management in 2021

Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome

Triple Negative Breast Cancer: Updates on Classification and Treatment in 2021

Breast cancer (BC) is the most common malignancy affecting women. It is a highly heterogeneous disease broadly defined by the differential expression of cell surface receptors. In the United States, triple negative breast cancer (TNBC) represents 15 to 20% of all BC. When compared with other subtypes of BC, TNBC tends to present in younger women, and has a higher mortality rate of 40% in advanced stages within the first 5 years after diagnosis. TNBC has historically had limited treatment options when compared to other types of BC. The mainstay of treatment for TNBC remains cytotoxic chemotherapy despite the emergence of new biologic and targeted agents. Defining the specific tumor molecular profile including PDL-1 and androgen receptor testing is expanding treatment options in the clinical setting. Identifying more targetable, novel biomarkers that may better define therapeutic targets or prognostic markers is currently underway. TNBC nomenclature is expected to be updated in favor of other nomenclature which would help direct therapy, and further redefine TNBC’s heterogeneity. Given the continuous advances in the field of TNBC, this review assesses the latest developments in basic characterization, subtyping, and treatment of TNBC, including novel drug developments with antibody-drug conjugates, immune checkpoint inhibitors, PARP inhibitors and androgen receptor targeted agents. Future trials are necessary in the face of these innovations to further support the use of new therapies in TNBC and the detection of the appropriate biomarkers

Single Cell RNA Sequencing: A New Frontier in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma is a malignancy with a high mortality rate. It exhibits significant heterogeneity in metabolic pathways which are associated with its progression. In this review, we discuss the role of single cell RNA sequencing in unraveling the metabolic and clinical features of these highly malignant tumors

The Lung Microbiota and Lung Cancer: A Growing Relationship

The lung is home to a dynamic microbial population crucial to modulating immune balance. Interest in the role of the lung microbiota in disease pathogenesis and treatment has exponentially increased. In lung cancer, early studies suggested an important role of dysbiosis in tumor initiation and progression. These results have helped accelerate research into the lung microbiota as a potential diagnostic marker and therapeutic target. Microbiota signatures could represent diagnostic biomarkers of early-stage disease. Lung microbiota research is in its infancy with a limited number of studies and only single-center studies with a significant methodological variation. Large, multicenter longitudinal studies are needed to establish the clinical potential of this exciting field

Liquid biopsies and minimal residual disease in lymphoid malignancies

Minimal residual disease (MRD) assessment using peripheral blood instead of bone marrow aspirate/biopsy specimen or the biopsy of the cancerous infiltrated by lymphoid malignancies is an emerging technique with enormous interest of research and technological innovation at the current time. In some lymphoid malignancies (particularly ALL), Studies have shown that MRD monitoring of the peripheral blood may be an adequate alternative to frequent BM aspirations. However, additional studies investigating the biology of liquid biopsies in ALL and its potential as an MRD marker in larger patient cohorts in treatment protocols are warranted. Despite the promising data, there are still limitations in liquid biopsies in lymphoid malignancies, such as standardization of the sample collection and processing, determination of timing and duration for liquid biopsy analysis, and definition of the biological characteristics and specificity of the techniques evaluated such as flow cytometry, molecular techniques, and next generation sequencies. The use of liquid biopsy for detection of minimal residual disease in T-cell lymphoma is still experimental but it has made significant progress in multiple myeloma for example. Recent attempt to use artificial intelligence may help simplify the algorithm for testing and may help avoid inter-observer variation and operator dependency in these highly technically demanding testing process

Drug Repurposing in Non-Small Cell Lung Carcinoma: Old Solutions for New Problems

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in 2022. The majority (80%) of lung cancer cases belong to the non-small cell lung carcinoma (NSCLC) subtype. Despite the increased screening efforts, the median five-year survival of metastatic NSCLC remains low at approximately 3%. Common treatment approaches for NSCLC include surgery, multimodal chemotherapy, and concurrent radio and chemotherapy. NSCLC exhibits high rates of resistance to treatment, driven by its heterogeneity and the plasticity of cancer stem cells (CSCs). Drug repurposing offers a faster and cheaper way to develop new antineoplastic purposes for existing drugs, to help overcome therapy resistance. The decrease in time and funds needed stems from the availability of the pharmacokinetic and pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved drugs to be repurposed. This review provides a synopsis of the drug-repurposing approaches and mechanisms of action of potential candidate drugs used in treating NSCLC, including but not limited to antihypertensives, anti-hyperlipidemics, anti-inflammatory drugs, anti-diabetics, and anti-microbials

Efficient synthesis of branched poly(acrylic acid) derivatives via postpolymerization modification

The utility of pentafluorophenyl esters for the selective introduction of functional units and branch points in well-defined poly(acrylic acid) (PAA) derivatives is demonstrated using a combination of controlled radical polymerization and postpolymerization modification. Reversible addition-fragmentation chain transfer enables the synthesis of well-defined copolymers-poly(pentafluorophenyl acrylate-co-tert-butyl acrylate)-with the active ester repeat units serving as attachment points for reaction with primary amines, specifically tris(2-(t-butoxycarbonyl)ethyl)methyl amine (Behera's amine). Deprotection using trifluoroacetic acid removes both the backbone and side chaint-butyl esters to give a series of branched PAA derivatives containing novel tricarboxylic acid side chains that are well suited to complexation and multidentate interactions. Surprisingly, the active ester homopolymer is shown to have the highest reactivity with Behera's amine when compared to copolymers with lower incorporation of pentafluorophenyl esters, suggesting an intriguing interplay of neighboring group effects and steric interactions. The ability to tune the efficiency of postpolymerization modification gives a library of PAA derivatives

Low‐temperature, rapid copolymerization of acrylic acid and sodium acrylate in water

Regulating the aqueous polymerization of acrylic acid (AA) is a major opportunity for future materials design, requiring the development of scalable, industry‐oriented procedures that afford modest molar mass and dispersity control without long reaction times and environmentally demanding conditions. To address these challenges, this report presents the rapid copolymerization of aqueous mixtures of AA and sodium acrylate using an inexpensive and scalable protocol based on alkyl iodides/sodium iodide as mediators in water

Scalable synthesis of an architectural library of well-defined poly(acrylic acid) derivatives: role of structure on dispersant performance

The synthesis and systematic comparison of a comprehensive library of well-defined polymer architectures based on poly(acrylic acid) is reported. Through the development of new synthetic methodologies, linear, single branched, precision-branched comb, and star polymers were prepared and their performance as dispersants was evaluated. The ability to accurately control chain lengths and branch points allows the subtle interplay between structure and dispersant performance to be defined and affords critical insights into the design of improved polymeric additives for coating formulations. The general industrial relevance of ionic polymers and branched macromolecular architectures supports these design rules for a wide range of other applications and materials, including as additives for personal care products and in water treatment. (c) 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 716-72