Old Paradoxes and New Opportunities for Appetite Control in Obesity.

Human obesity is accompanied by alterations in the blood concentrations of multiple circulating appetite regulators. Paradoxically, most of the appetite-inhibitory hormones are elevated in nonsyndromic obesity, while most of the appetite stimulatory hormones are reduced, perhaps reflecting vain attempts of regulation by inefficient feedback circuitries. In this context, it is important to understand which appetite regulators exhibit a convergent rather than paradoxical behavior and hence are likely to contribute to the maintenance of the obese state.

SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation.

Introduction: The use of immune-checkpoint inhibitors has drastically improved the management of patients with non-small cell lung cancer (NSCLC), but innate and acquired resistances are hurdles needed to be solved. Immunomodulatory drugs that can reinvigorate the immune cytotoxic activity, in combination with antiprogrammed cell death 1 (PD-1) antibody, are a great promise to overcome resistance. We evaluated the impact of the SRC family kinases (SFKs) on NSCLC prognosis, and the immunomodulatory effect of the SFK inhibitor dasatinib, in combination with anti-PD-1, in clinically relevant mouse models of NSCLC.

A novel LysR-type regulator negatively affects biosynthesis of the immunosuppressant brasilicardin.

Brasilicardin A (BraA) is a promising immunosuppressive compound produced naturally by the pathogenic bacterium IFM 0406. Heterologous host expression of brasilicardin gene cluster showed to be efficient to bypass the safety issues, low production levels and lack of genetic tools related with the use of native producer. Further improvement of production yields requires better understanding of gene expression regulation within the BraA biosynthetic gene cluster (Bra-BGC); however, the only so far known regulator of this gene cluster is Bra12.

A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.

Background: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance.

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation.

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS).

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma.

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes.

Tumor-Infiltrating CD20 B Lymphocytes: Significance and Prognostic Implications in Oral Cancer Microenvironment.

Immunohistochemical analysis of stromal/tumoral CD20 B lymphocytes was performed in 125 OSCC patients. Correlations with immune profiles CD4, CD8, and FOXP3 tumor-infiltrating lymphocytes (TILs), tumoral PD-L1, and stem-related factors NANOG and SOX2 were assessed, and also associations with clinical data and patient survival. There was a strong positive correlation between the infiltration of CD20 B lymphocytes and other immune profiles (i.

Influence of Kv11.1 (hERG1) K channel expression on DNA damage induced by the genotoxic agent methyl methanesulfonate.

Besides their crucial role in cell electrogenesis and maintenance of basal membrane potential, the voltage-dependent K channel Kv11.1/hERG1 shows an essential impact in cell proliferation and other processes linked to the maintenance of tumour phenotype. To check the possible influence of channel expression on DNA damage responses, HEK293 cells, treated with the genotoxic agent methyl methanesulfonate (MMS), were compared with those of a HEK-derived cell line (H36), permanently transfected with the Kv11.

The presence of dysphagia in patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): a subjective and objective study.

Purpose: The aim of this study was to determine the prevalence of dysphagia in patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), characterizing this condition, both in its objective dimension and in terms of quality of life (QoL).

Methods: A cross-sectional study was developed in 11 patients diagnosed of CANVAS. In all patients, clinical records were reviewed and the Eating assessment tool 10 (EAT-10) was performed as screening of oropharyngeal dysphagia.

A capsaicinoid-based soft drug, AG1529, for attenuating TRPV1-mediated histaminergic and inflammatory sensory neuron excitability.

TRPV1, a member of the transient receptor potential (TRP) family, is a nonselective calcium permeable ion channel gated by physical and chemical stimuli. In the skin, TRPV1 plays an important role in neurogenic inflammation, pain and pruritus associated to many dermatological diseases. Consequently, TRPV1 modulators could represent pharmacological tools to respond to important patient needs that still represent an unmet medical demand.

Blockage of Squamous Cancer Cell Collective Invasion by FAK Inhibition Is Released by CAFs and MMP-2.

Metastasis remains a clinically unsolved issue in cancer that is initiated by the acquisition of collective migratory properties of cancer cells. Phenotypic and functional heterogeneity that arise among cancer cells within the same tumor increase cellular plasticity and promote metastasis, however, their impact on collective cell migration is incompletely understood. Here, we show that in vitro collective cancer cell migration depends on FAK and MMP-2 and on the presence of cancer-associated fibroblasts (CAFs).

Stathmin as a surrogate marker of phosphatidylinositol-3-kinase pathway activity: Towards precision medicine in HPV-negative head & neck squamous cell carcinoma.

In order to assess Stathmin as an immunohistochemical (IHC) indicator of phosphatidylinositol 3-kinase (PI3K) pathway activity in HPV-negative head & neck squamous cell carcinoma (HNSCC), we compared Stathmin IHC to expression of other pathway components. We also evaluated the relationship between Stathmin IHC and the mutational status of four key pathway genes. Finally, we ascertained whether Stathmin IHC correlates with tumor grade or primary site.

Lectin-Like Transcript 1 (LLT1) Checkpoint: A Novel Independent Prognostic Factor in HPV-Negative Oropharyngeal Squamous Cell Carcinoma.

Lectin-like transcript 1 (LLT1) expression by tumor cells contributes to immune evasion, thereby emerging as a natural killer (NK) cell-mediated immunotherapeutic target. This study is the first to investigate LLT1 expression (encoded by gene) in head and neck cancers to ascertain its impact on patient prognosis. LLT1 expression was analyzed by immunohistochemistry in a homogeneous cohort of human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinomas (OPSCC), and correlated with clinical data.

Cellular and molecular features of senescence in acute lung injury.

A wide range of insults can trigger acute injury in the lungs, which eventually may lead to respiratory failure and death of patients. Current treatment relies mainly on supportive measures and mechanical ventilation. Even so, survivors frequently develop important sequels that compromise quality of life.

Driver Mutations and Single Copy Number Abnormalities Identify Binet Stage A Patients with Chronic Lymphocytic Leukemia with Aggressive Progression.

The correlation between progression and the genetic characteristics of Binet stage A patients with chronic lymphocytic leukemia (CLL) detected by whole exome sequencing (WES) was analyzed in 55 patients. The median follow-up for the patients was 102 months. During the follow-up, 24 patients (43%) progressed.

Behaviour of citrus pectin and modified citrus pectin in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced rat colorectal carcinogenesis model.

Large intestine cancer is one of the most relevant chronic diseases taking place at present. Despite therapies have evolved very positively, this pathology is still under deep investigation. One of the recent approaches is the prevention by natural compounds such as pectin.

Prognostic role of intraparotid lymph node metastasis in primary parotid cancer: Systematic review.

Background: The prognostic importance of intraparotid lymph node metastasis (P+) in patients with primary parotid gland carcinoma is unclear.

Methods: Nineteen retrospective and noncomparative cohort studies, published between 1992 and 2020, met the inclusion criteria and included 2202 patients for this systematic review.

Results: The pooled prevalence of the P in adult patients in the unselected studies was 24.

Electronic Cigarettes and Head and Neck Cancer Risk-Current State of Art.

E-cigarettes have become increasingly popular in the last decade and are considered less harmful than traditional tobacco products due to the lower content of toxic and carcinogenic compounds. However, this is still a controversial issue. This paper contains a review of previous reports on the composition of e-cigarettes and their impact on the pathogenesis and risk of head and neck cancer (HNC).

A low pKa ligand inhibits cancer-associated pain in mice by activating peripheral mu-opioid receptors.

The newly designed fentanyl derivative [( ±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide] (NFEPP) was recently shown to produce analgesia selectively via peripheral mu-opioid receptors (MOR) at acidic pH in rat inflamed tissues. Here, we examined the pH-dependency of NFEPP binding to brain MOR and its effects on bone cancer-induced pain in mice. The IC of NFEPP to displace bound [H]-DAMGO was significantly higher compared to fentanyl at pH 7.

The Interferon-induced transmembrane protein 3 gene (IFITM3) rs12252 C variant is associated with COVID-19.

Background And Aims: The interferon-induced transmembrane proteins play an important antiviral role by preventing viruses from traversing the cellular lipid bilayer. IFITM3 gene variants have been associated with the clinical response to influenza and other viruses. Our aim was to determine whether the IFITM3 rs12252 polymorphism was associated with the risk of developing severe symptoms of COVID-19 in our population.

Repositioning microbial biotechnology against COVID-19: the case of microbial production of flavonoids.

Coronavirus-related disease 2019 (COVID-19) became a pandemic in February 2020, and worldwide researchers try to tackle the disease with approved drugs of all kinds, or to develop novel compounds inhibiting viral spreading. Flavonoids, already investigated as antivirals in general, also might bear activities specific for the viral agent causing COVID-19, SARS-CoV-2. Microbial biotechnology and especially synthetic biology may help to produce flavonoids, which are exclusive plant secondary metabolites, at a larger scale or indeed to find novel pharmaceutically active flavonoids.

Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma.

Objectives: The function of NOTCH signaling (oncogenic or oncosuppressive) remains controversial in head and neck squamous cell carcinomas (HNSCC). The purpose of this work is to investigate the role of NOTCH pathway in HNSCC prognosis.

Methods: Immunohistochemical NOTCH1 and HES1 expression was jointly evaluated and correlated with other NOTCH1 targets, p21 (WAF1/Cip1) and Cyclin D1, using an unbiased cohort of 372 surgically treated HPV-negative HNSCC patients.

Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome.

The Angiotensin system is implicated in the pathogenesis of COVID-19. First, ACE2 is the cellular receptor for SARS-CoV-2, and expression of the ACE2 gene could regulate the individuaĺs susceptibility to infection. In addition, the balance between ACE1 and ACE2 activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID-19.