Vibrational spectroscopy coupled with machine learning sheds light on the cellular effects induced by rationally designed TLR4 agonists.

In this work, we present the potential of Fourier transform infrared (FTIR) microspectroscopy to compare on whole cells, in an unbiased and untargeted way, the capacity of bacterial lipopolysaccharide (LPS) and two rationally designed molecules (FP20 and FP20Rha) to activate molecular circuits of innate immunity. These compounds are important drug hits in the development of vaccine adjuvants and tumor immunotherapeutics. The biological assays indicated that FP20Rha was more potent than FP20 in inducing cytokine production in cells and in stimulating IgG antibody production post-vaccination in mice.

Novel TLR4-Activating Vaccine Adjuvant Enhances the Production of -binding Antibodies.

Vaccines are one of the greatest achievements of modern medicine. Due to their safer profile, the latest investigations usually focus on subunit vaccines. However, the active component often needs to be coupled with an adjuvant to be effective and properly trigger an immune response.

Current Approach to Dysphagia: A Review Focusing on Esophageal Motility Disorders and Their Treatment.

Background: Dysphagia is a prevalent condition which may severely impact the patient's quality of life. However, there are still lacking standardized therapeutic options for esophageal motility disorders.

Summary: Dysphagia is defined as a subjective sensation of difficulty swallowing which can result from oropharyngeal or esophageal etiologies.

Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

Background And Aims: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries.

Methods: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases.

Overcoming Challenges in Chemical Glycosylation to Achieve Innovative Vaccine Adjuvants Possessing Enhanced TLR4 Activity.

Lipopolysaccharide (LPS) mimicry leading to toll-like receptor 4 (TLR4) active compounds has been so far based mainly on reproducing the lipid A portion of LPS. Our work led to a series of structurally simplified synthetic TLR4 agonists in preclinical development as vaccine adjuvants called FPs. FPs bind MD2/TLR4 similarly to lipid A, inserting the lipid chains in the MD2 lipophilic cavity.

Use of Fluorescent Chemical Probes in the Study of Toll-like Receptors (TLRs) Trafficking.

Fluorescent chemical probes are used nowadays as a chemical resource to study the physiology and pharmacology of several important endogenous receptors. Different fluorescent groups have been coupled with known ligands of these receptors, allowing the visualization of their localization and trafficking. One of the most important molecular players of innate immunity and inflammation are the Toll-Like Receptors (TLRs).

Early intervention with biologic therapy in Crohn´s disease: how early is early?

Background: Early biologic therapy within the first 18-24 months after diagnosis is associated with improved clinical outcomes in Crohn's disease [CD]. However, the definition of the best time to initiate biologic therapy remains unclear. We aimed to assess if there is an optimal timing for early biologic therapy initiation.

New Glucosamine-Based TLR4 Agonists: Design, Synthesis, Mechanism of Action, and In Vivo Activity as Vaccine Adjuvants.

We disclose here a panel of small-molecule TLR4 agonists (the series) whose structure is derived from previously developed TLR4 ligands ( series). The new molecules have increased chemical stability and a shorter, more efficient, and scalable synthesis. The series showed selective activity as TLR4 agonists with a potency similar to .

Endoscopic Submucosal Dissection for Resections Larger than 10 cm: Outcomes from a Portuguese Center.

Background: Endoscopic submucosal dissection (ESD) is a minimally invasive technique for en bloc resection of superficial neoplastic lesions, independent of their size. However, for giant gastrointestinal superficial neoplasia, the risk of invasive cancer is higher, and ESD is typically challenging. Despite the increasing literature on giant resections, data on their efficacy and safety are still lacking.

A Global Picture of Molecular Changes Associated to LPS Treatment in THP-1 Derived Human Macrophages by Fourier Transform Infrared Microspectroscopy.

Macrophages are among the first immune cells involved in the initiation of the inflammatory response to protect the host from pathogens. THP-1 derived macrophages (TDM) are used as a model to study the pro-inflammatory effects of lipopolysaccharide (LPS) exposure. Intact TDM cells were analysed by Fourier transform infrared (FTIR) microspectroscopy, supported by multivariate analysis, to obtain a snapshot of the molecular events sparked by LPS stimulation in macrophage-like cells.

A "window" in the duodenal bulb: an atypical presentation of chronic cholecystitis.

A 74-year-old male presented with melena and fatigue, without fever or abdominal pain. Laboratory examination revealed anemia, leukocytosis, elevated C-reactive protein levels and conjugated hyperbilirubinemia with elevated liver enzymes. Upper endoscopy identified blood in the stomach and duodenum and a 6 mm hole in the anterosuperior surface of the duodenal bulb with spontaneous drainage of a bloody brownish content.

HSV-1 hepatitis in an immunocompetent patient - Act before you know.

Herpes simplex virus type 1 (HSV-1) hepatitis is an unusual complication of HSV infection, which frequently results in acute liver failure. Even though the most affected individuals are immunosuppressed patients, around 25 % patients who present with HSV hepatitis are immunocompetent. We report a case of an anicteric febrile hepatitis in a 46-year-old immunocompetent women in which the early suspicion of HSV hepatitis allowed empirical treatment and later diagnosis confirmation by liver biopsy.

Developing New Anti-Tuberculosis Vaccines: Focus on Adjuvants.

Tuberculosis (TB) is an infectious disease caused by (Mtb) that sits in the top 10 leading causes of death in the world today and is the current leading cause of death among infectious diseases. Although there is a licensed vaccine against TB, the bacilli Calmette-Guérin (BCG) vaccine, it has several limitations, namely its high variability of efficacy in the population and low protection against pulmonary tuberculosis. New vaccines for TB are needed.