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Head and neck squamous cell carcinoma (HNSCC) encompass a group of complex entities of tumours affecting the aerodigestive upper tract. The main risk factors are strongly related to tobacco and alcohol consumption, but also HPV infection is often associated. Surgery, radiotherapy and/or chemotherapy are the standard treatments, though the 5-year overall survival is less than 50%. The advances in genomics, molecular medicine, immunology, and nanotechnology have shed a light on tumour biology which helps clinical researchers to obtain more efficacious and less toxic therapies. Head and neck tumours possess different immune escape mechanisms including diminishing the immune response through modulating immune checkpoints, in addition to the recruitment and differentiation of suppressive immune cells. The insights into the HNSCC biology and its strong interaction with the tumour microenvironment highlights the role of immunomodulating agents. Recently, the knowledge of the immunological features of these tumours has paved the way for the discovery of effective biomarkers that allow a better selection of patients with odds of improving overall survival through immunotherapy. Specially biomarkers regarding immune checkpoint inhibitors antibodies, such as anti-PD-1/PD-L1 and anti-CTLA-4 in combination with standard therapy or as monotherapy. New immunotherapies to treat head and neck cancer carcinomas, such as CAR T cells and nanoparticles have been the center of attention and in this review, we discuss the necessity of finding targets for the T cell in the cancer cells to generate CAR T cells, but also the relevance of evaluating specificity and safety of those therapies. [ABSTRACT FROM AUTHOR]

In this paper, a localized surface plasmon resonance (LSPR)‐based biosensor, computationally guided to detect selectively the four Dengue virus (DENVx) serotypes in seropositive patients, is presented. The behavior of gold nanoparticles in the shape of nanorods is theoretically and numerically studied as a function of induced structural variations, which are experimentally evidenced due to the bio‐interaction between the target analytes and its surface during the detection process. Additionally, with the implementation of the largest Lyapunov exponent, it is possible to calculate the notion of predictability for the experimental results, observing chaotic systems with a very low probability of repetition. Due to the above, when analyzing the recurrence map associated with the obtained resonance curve generated by the LSPR system, the genetic similarity of DENV3/DENV2 and DENV4/DENV1 is evidenced. Finally, the biosensors are validated by analyzing samples of seronegative patients for DENVx and seropositive ones for other Flaviviruses such as Zika virus, Yellow Fever virus, and Saint Louis Encephalitis virus. [ABSTRACT FROM AUTHOR]

By analysing the evolution of the COVID‐19 epidemic in the state of Minas Gerais, Brazil, we showed the importance of considering the sub‐notification not only of deaths but also of infected cases. It was shown that the largely used criteria of a historical all‐deaths baseline are not approachable in this case, where most of the deaths are associated with causes that should decrease due to social distancing and reduction of economic activities. A quite simple and intuitive model based on the Gompertz function was applied to estimate excess deaths and excess of infected cases. It fits well the data and predicts the evolution of the epidemic adequately. Based on these analyses, an excess of 21.638 deaths and 557.216 infected cases is predicted until the end of 2020, with an upper bound of the case fatality rate of around 2.4% and a prevalence of 2.6%. The geographical distribution of cases and deaths and its ethnic correlation are also presented. This study points out the necessity of governmental and private organizations working together to improve public awareness and stimulate social distancing to curb the viral infection, especially in critical places with high poverty. [ABSTRACT FROM AUTHOR]

Flow cytometry is a universally applied technique in many biological and clinical assays to evaluate cells, bacteria, parasites, and particles at a micrometre scale. More advanced flow cytometers can detect small molecules down to the nanometre scale that may identify intracellular nanostructures. Advancements in the field of nanobiotechnology have led to techniques that allow the study of cellular behaviour after exposure to nanomaterials, particularly, metal nanoparticles. The optical properties of gold nanoparticles regarding surface plasmon resonance (SPR) are established to increase the fluorescence quantum yields of several dyes working as optical antennas, enabling the enhancement of light emission in fluorescent emitters. In this work we constructed a nanoprobe using gold nanoparticles coated with primary antibody Cetuximab. Then, we investigated whether this nanoprobe labelled with secondary fluorescent antibody Alexa Fluor 488, at low concentrations, could promote fluorescent signal enhancement, associated with SPR, and detected by the flow cytometry technique. Our results showed an enhanced fluorescent signal likely due to the proximity between the extinction coefficient of gold nanoparticles and the emission peak of Alexa Fluor 488, at exceptionally low concentrations, occurring within a high level of specificity. Moreover, the nanoprobe did not alter the cellular viability suggesting gold nanoparticles as a feasible approach for cell labelling using low concentrations of secondary antibodies for routine flow cytometry applications. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) is an essential signal transduction element involved in the regulation of several cellular activities and it is required at various key stages of the cell cycle. Intracellular Ca2+ is crucial for the orderly cell cycle progression and plays a vital role in the regulation of cell proliferation. Recently, it was demonstrated by in vitro and in vivo studies that nucleoplasmic Ca2+ regulates cell growth. Even though the mechanism by which nuclear Ca2+ regulates cell proliferation is not completely understood, there are reports demonstrating that activation of tyrosine kinase receptors (RTKs) leads to translocation of RTKs to the nucleus to generate localized nuclear Ca2+ signaling which are believed to modulate cell proliferation. Moreover, nuclear Ca2+ regulates the expression of genes involved in cell growth. This review will describe the nuclear Ca2+ signaling machinery and its role in cell proliferation. Additionally, the potential role of nuclear Ca2+ as a target in cancer therapy will be discussed. [ABSTRACT FROM AUTHOR]

Background: Adenosine triphosphate (ATP) is secreted from hepatocytes under physiological conditions and plays an important role in liver biology through the activation of P2 receptors. Conversely, higher extracellular ATP concentrations, as observed during necrosis, trigger inflammatory responses that contribute to the progression of liver injury. Impaired calcium (Ca2+) homeostasis is a hallmark of acetaminophen (APAP)-induced hepatotoxicity, and since ATP induces mobilization of the intracellular Ca2+ stocks, we evaluated if the release of ATP during APAP-induced necrosis could directly contribute to hepatocyte death. Results: APAP overdose resulted in liver necrosis, massive neutrophil infiltration and large non-perfused areas, as well as remote lung inflammation. In the liver, these effects were significantly abrogated after ATP metabolism by apyrase or P2X receptors blockage, but none of the treatments prevented remote lung inflammation, suggesting a confined local contribution of purinergic signaling into liver environment. In vitro, APAP administration to primary mouse hepatocytes and also HepG2 cells caused cell death in a dose-dependent manner. Interestingly, exposure of HepG2 cells to APAP elicited significant release of ATP to the supernatant in levels that were high enough to promote direct cytotoxicity to healthy primary hepatocytes or HepG2 cells. In agreement to our in vivo results, apyrase treatment or blockage of P2 receptors reduced APAP cytotoxicity. Likewise, ATP exposure caused significant higher intracellular Ca2+ signal in APAP-treated primary hepatocytes, which was reproduced in HepG2 cells. Quantitative real time PCR showed that APAP-challenged HepG2 cells expressed higher levels of several purinergic receptors, which may explain the hypersensitivity to extracellular ATP. This phenotype was confirmed in humans analyzing liver biopsies from patients diagnosed with acute hepatic failure. Conclusion: We suggest that under pathological conditions, ATP may act not only an immune system activator, but also as a paracrine direct cytotoxic DAMP through the dysregulation of Ca2+ homeostasis. [ABSTRACT FROM AUTHOR]