The Cytokine Mediated Molecular Pathophysiology of Psoriasis and Its Clinical Implications

Psoriasis is the result of uncontrolled keratinocyte proliferation, and its pathogenesis involves the dysregulation of the immune system. The interplay among cytokines released by dendritic, Th1, Th2, and Th17 cells leads to the phenotypical manifestations seen in psoriasis. Biological therapies target the cytokine-mediated pathogenesis of psoriasis and have improved patient quality of life. This review will describe the underlying molecular pathophysiology and biologics used to treat psoriasis. A review of the literature was conducted using the PubMed and Google Scholar repositories to investigate the molecular pathogenesis, clinical presentation, and current therapeutics in psoriasis. Plaque psoriasis’, the most prevalent subtype of psoriasis, pathogenesis primarily involves cytokines TNF-α, IL-17, and IL-23. Pustular psoriasis’, an uncommon variant, pathogenesis involves a mutation in IL-36RN. Currently, biological therapeutics targeted at TNF-α, IL-12/IL-23, IL-17, and IL-23/IL-39 are approved for the treatment of moderate to severe psoriasis. More studies need to be performed to elucidate the precise molecular pathology and assess efficacy between biological therapies for psoriasis. Psoriasis is a heterogenous, chronic, systemic inflammatory disease that presents in the skin with multiple types. Recognizing and understanding the underlying molecular pathways and biological therapeutics to treat psoriasis is important in treating this common disease.

Cameroonian Spice Extracts Modulate Molecular Mechanisms Relevant to Cardiometabolic Diseases in SW 872 Human Liposarcoma Cells

The molecular pathophysiology of cardiometabolic diseases is known to be influenced by dysfunctional ectopic adipose tissue. In addition to lifestyle improvements, these conditions may be managed by novel nutraceutical products. This study evaluatedthe effects of 11 Cameroonian medicinal spice extracts on triglyceride accumulation, glucose uptake, reactive oxygen species (ROS) production and interleukin secretion in SW 872 human adipocytes after differentiation with 100 µM oleic acid. Triglyceride content was significantly reduced by all spice extracts. Glucose uptake was significantly increased by Tetrapleura tetraptera, Aframomum melegueta and Zanthoxylum leprieurii. Moreover, Xylopia parviflora, Echinops giganteus and Dichrostachys glomerata significantly reduced the production of ROS. Concerning pro-inflammatory cytokine secretion, we observed that Tetrapleura tetraptera, Echinops giganteus, Dichrostachys glomerata and Aframomum melegueta reduced IL-6 secretion. In addition, Xylopia parviflora, Monodora myristica, Zanthoxylum leprieurii, and Xylopia aethiopica reduced IL-8 secretion, while Dichrostachys glomerata and Aframomum citratum increased it. These findings highlight some interesting properties of these Cameroonian spice extracts in the modulation of cellular parameters relevant to cardiometabolic diseases, which may be further exploited, aiming to develop novel treatment options for these conditions based on nutraceutical products.

Anticoagulation Treatment in Venous Thromboembolism: Options and Optimal Duration

: Venous thromboembolism (VTE), clinically presenting as deep-vein thrombosis (DVT) or pulmonary embolism (PE), constitutes a major global healthcare concern with severe complications, long-term morbidity and mortality. Although several clinical, genetic and acquired risk factors for VTE have been identified, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. Anticoagulation has been the cornerstone of therapy for decades, but there still are uncertainties regarding primary and secondary VTE prevention, as well as optimal therapy duration. In this review we discuss the role of factor Xa in coagulation cascade and the different choices of anticoagulation therapy based on patients’ predisposing risk factors and risk of event recurrence. Further, we compare newer agents to traditional anticoagulation treatment, based on most recent studies and guidelines.

Reconstituting Immune Surveillance in Breast Cancer: Molecular Pathophysiology and Current Immunotherapy Strategies

Over the past 50 years, breast cancer immunotherapy has emerged as an active field of research, generating novel, targeted treatments for the disease. Immunotherapies carry enormous potential to improve survival in breast cancer, particularly for the subtypes carrying the poorest prognoses. Here, we review the mechanisms by which cancer evades immune destruction as well as the history of breast cancer immunotherapies and recent developments, including clinical trials that have shaped the treatment of the disease with a focus on cell therapies, vaccines, checkpoint inhibitors, and oncolytic viruses.

Brugada syndrome: update and future perspectives

Brugada syndrome (BrS) is an inherited cardiac disorder, characterised by a typical ECG pattern and an increased risk of arrhythmias and sudden cardiac death (SCD). BrS is a challenging entity, in regard to diagnosis as well as arrhythmia risk prediction and management. Nowadays, asymptomatic patients represent the majority of newly diagnosed patients with BrS, and its incidence is expected to rise due to (genetic) family screening. Progress in our understanding of the genetic and molecular pathophysiology is limited by the absence of a true gold standard, with consensus on its clinical definition changing over time. Nevertheless, novel insights continue to arise from detailed and in-depth studies, including the complex genetic and molecular basis. This includes the increasingly recognised relevance of an underlying structural substrate. Risk stratification in patients with BrS remains challenging, particularly in those who are asymptomatic, but recent studies have demonstrated the potential usefulness of risk scores to identify patients at high risk of arrhythmia and SCD. Development and validation of a model that incorporates clinical and genetic factors, comorbidities, age and gender, and environmental aspects may facilitate improved prediction of disease expressivity and arrhythmia/SCD risk, and potentially guide patient management and therapy. This review provides an update of the diagnosis, pathophysiology and management of BrS, and discusses its future perspectives.

The molecular pathophysiology of mood disorders: from the analysis of single molecular layers to multi-omic integration.

Next-generation sequencing now enables the rapid and affordable production of reliable biological data at multiple molecular levels, collectively referred to as “omics”. To maximize the potential for discovery, computational biologists have created and adapted integrative multiomic analytical methods. When applied to diseases with traceable pathophysiology such as cancer, these new algorithms and statistical approaches have enabled the discovery of clinically relevant molecular mechanisms and biomarkers. In contrast, these methods have been much less applied to the field of molecular psychiatry, although diagnostic and prognosticbiomarkers are similarly needed. In the present review, we first briefly summarize main findings from two decades of studies that investigated single molecular processes in relation to mood disorders. Then, we conduct a systematic review of multi-omic strategies that have been proposed and used more recently. We also list databases and types of data available to researchers for future work. Finally, we present the newest methodologies that have been employed for multi-omics integration in other medical fields, and discuss their potential for molecular psychiatry studies.

Histone Deacetylases and their Inhibitors in Colorectal Cancer Therapy: Current Evidence and Future Considerations

: Colorectal cancer (CRC) comprises a heterogeneous group of gastrointestinal tract tumors. It is a multifactorial disease, and a plethora of distinct factors are involved in its pathogenesis and pathophysiology. The development of CRC is not limited to genetic changes, but epigenetic and environmental factors are also involved. Among the epigenetic factors, histone deacetylases (HDACs), a group of epigenetic enzymes that regulate gene expression, have been reported to be over-expressed in CRC. HDACs and their inhibitors seem to play an important role in the molecular pathophysiology of CRC. The aim of this review was to define the role of HDAC inhibitors as potential anticancer agents against CRC.

Molecular Classification of Knee Osteoarthritis

Knee osteoarthritis (KOA) is the most common form of joint degeneration with increasing prevalence and incidence in recent decades. KOA is a molecular disorder characterized by the interplay of numerous molecules, a considerable number of which can be detected in body fluids, including synovial fluid, urine, and blood. However, the current diagnosis and treatment of KOA mainly rely on clinical and imaging manifestations, neglecting its molecular pathophysiology. The mismatch between participants’ molecular characteristics and drug therapeutic mechanisms might explain the failure of some disease-modifying drugs in clinical trials. Hence, according to the temporal alteration of representative molecules, we propose a novel molecular classification of KOA divided into pre-KOA, early KOA, progressive KOA, and end-stage KOA. Then, progressive KOA is furtherly divided into four subtypes as cartilage degradation-driven, bone remodeling-driven, inflammation-driven, and pain-driven subtype, based on the major pathophysiology in patient clusters. Multiple clinical findings of representatively investigated molecules in recent years will be reviewed and categorized. This molecular classification allows for the prediction of high-risk KOA individuals, the diagnosis of early KOA patients, the assessment of therapeutic efficacy, and in particular, the selection of homogenous patients who may benefit most from the appropriate therapeutic agents.

Molecular pathophysiology in infection by Helicobacter pylori

La infección por Helicobacter pylori es la infección bacteriana más común a nivel mundial, en 1994 la Agencia Internacional para la Investigación en Cáncer catalogó al Helicobacter Pylori como un carcinógeno tipo I. La infección por ésta bacteria incrementa el riesgo de padecer cáncer gástrico hasta 6 veces más que los individuos que no presentan la infección. Colombia tiene una prevalencia de infección por Helicobacter pylori del 86% en adultos mayores de 20 años y del 80% en niños mayores de 8 años. La infección persistente y recidivante de la mucosa gástrica puede generar una respuesta inflamatoria, o procesos silentes, que en el peor de los casos puede progresar a un adenocarcinoma gástrico tipo difuso o intestinal. Existen múltiples factores que influyen en las consecuencias clínicas de la infección por Helicobacter pylori, en mención: predisposición genética del huésped, inmunorregulación genética del paciente infectado, factores ambientales y heterogeneidad de los factores de virulencia de las diversas cepas. Por lo anterior se infiere que las patologías gástricas, en especial la gastritis y el adenocarcinoma, son padecimientos de etiología multifactorial que pueden originarse por diversas causas o condiciones. En la presente revisión se analizarán los principales aspectos relacionados con la fisiopatología molecular en la infección por Helicobacter pylori, en particular tópicos correspondientes a los factores de virulencia.