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Topic Review
Alzheimer′s Disease Really Start
While Alzheimer’s disease (AD) classical diagnostic criteria rely on clinical data from a stablished symptomatic disease, newer criteria aim to identify the disease in its earlier stages. For that, they incorporated the use of AD’s specific biomarkers to reach a diagnosis, including the identification of Aβ and tau depositions, glucose hypometabolism, and cerebral atrophy. These biomarkers created a new concept of the disease, in which AD’s main pathological processes have already taken place decades before we can clinically diagnose the first symptoms. Therefore, AD is now considered a dynamic disease with a gradual progression, and dementia is its final stage. With that in mind, new models were proposed, considering the orderly increment of biomarkers and the disease as a continuum, or the variable time needed for the disease’s progression. In 2011, the National Institute on Aging and the Alzheimer’s Association (NIA-AA) created separate diagnostic recommendations for each stage of the disease continuum—preclinical, mild cognitive impairment, and dementia. However, new scientific advances have led them to create a unifying research framework in 2018 that, although not intended for clinical use as of yet, is a step toward shifting the focus from the clinical symptoms to the biological alterations and toward changing the future diagnostic and treatment possibilities. 
  • 1.4K
  • 30 Oct 2020
Topic Review
SARS-CoV-2 Infection
The SARS-CoV-2 pandemic represents the focus of the biomedical research worldwide. The identification of the molecular events related to the SARS-CoV-2 infection, as well as the characterization of its clinical features, could put an end to this dramatic health emergency. In this scenario, the interpretation of histopathological data in light of the clinical imaging characteristics of SARS-CoV-2 infection can provide the scientific rationale to develop diagnostic and therapeutic protocols that are capable of improving the management of infected patients. Specifically, morphological and molecular analysis of SARS-CoV-2 infected tissues could highlight new useful prognostic and predictive biomarkers for in vivo investigations.
  • 1.4K
  • 06 Nov 2020
Topic Review
Predicting Response to Immune-Checkpoint Inhibition
The therapeutic concept of unleashing a pre-existing immune response against the tumor by the application of immune-checkpoint inhibitors (ICI) has resulted in long-term survival in advanced cancer patient subgroups. Established biomarkers such as programmed death ligand 1 (PD-L1) and tumor mutational burden (TMB) help to select patients who will most likely benefit from ICI, however, biomarker negativity does not exclude responses. Investigating alterations in the antigen presenting pathway as well as radiomics have the potential to determine tumor immunogenicity and response to ICI. A plethora of steps is crucial for proper tumor neoantigen presentation and T cell recognition. Alterations in the antigen presenting pathway give rise to resistance mechanisms that in turn abolish the effect of ICI. Tumor neoantigen prediction models have been shown to identify cancer patients who benefit most from immune-checkpoint blockade, however, a high false positive rate is a drawback of these models. The predictive value of already established biomarkers is considerably heterogeneous across various malignancies and intratumoral and intrapatient heterogeneity complicate tumor tissue-based biomarker assessment. Radiomics offers the opportunity to evaluate biomarkers based on imaging studies without the necessity to perform tumor tissue biopsies. Several radiomics studies have shown to predict clinical outcome with ICI. Radiomics might also help to identify patients who are at risk for hyperprogressive disease upon initiation of anti-PD-1/anti-PD-L1 therapy and patients who are at risk for high grade immune-related adverse events.
  • 1.4K
  • 29 Oct 2020
Topic Review
Reactive Oxygen Species and Oxidative Stress in Stroke
Stroke is one of the leading causes of morbidity and mortality worldwide. A main cause of brain damage by stroke is ischemia-reperfusion (IR) injury due to the increased production of reactive oxygen species (ROS) and energy failure caused by changes in mitochondrial metabolism. Reverse electron transfer (RET) has been implicated in excessive ROS production during IR injury in stroke and new insights into the mechanism of RET gained from various systems in recent studies will help understand stroke pathophysiology and inform therapy.
  • 1.4K
  • 18 Apr 2023
Topic Review
Pruritus Pathogenesis in Psoriasis
Psoriasis is a chronic, systemic inflammatory disease with a genetic background that involves almost 3% of the general population worldwide. About 70-80% of psoriatic patients suffer from pruritus. Despite its high prevalence in psoriasis, its pathogenesis still remains unclear. 
  • 1.4K
  • 22 Sep 2021
Topic Review
Autophagy-ER Stress Axis in High Fat/Carbohydrate Diet-Induced Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease that can progress from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), and even further to liver cirrhosis or liver cancer. Overconsumption of high fat and/or carbohydrate are among the most common lifestyle factors that drive the development and progression of NAFLD. This review evaluates recent reports on the involvement of autophagy and endoplasmic reticulum (ER) stress in the pathogenesis of NAFLD. Here, we reveal a mechanism of an intrinsically linked axis of impaired autophagy and unresolved ER stress that mediates the development and progression of NAFLD resulting from the overconsumption of high fat and/or carbohydrate.
  • 1.4K
  • 05 Nov 2020
Topic Review
Nipah Virus Disease
Nipah virus (NiV) infection is a viral disease caused by a Henipavirus, belonging to the Paramyxoviridae family, responsible for a zoonosis. The course of the disease can be very serious and lead to death. NiV natural hosts are fruit bats (also known as megabats) belonging to the Pteropodidae family, especially those of the Pteropus genus. Natural infection in domestic animals has been described in farming pigs, horses, domestic and feral dogs and cats. Natural NiV transmission is possible intra-species (pig-to-pig, human-to-human) and inter-species (flying bat-to-human, pig-to-human, horse-to-human).
  • 1.4K
  • 11 Jan 2023
Topic Review
Latin-American Genes in Rheumatoid Arthritis
The successful implementation of personalized medicine will rely on the integration of information obtained at the level of populations with the specific biological, genetic, and clinical characteristics of an individual. However, because genome-wide association studies tend to focus on populations of European descent, there is a wide gap to bridge between Caucasian and non-Caucasian populations before personalized medicine can be fully implemented, and rheumatoid arthritis (RA) is not an exception. In this review, we discuss advances in our understanding of genetic determinants of RA risk among global populations, with a focus on the Latin American population. Geographically restricted genetic diversity may have important implications for health and disease that will remain unknown until genetic association studies have been extended to include Latin American and other currently under-represented ancestries. The next few years will witness many breakthroughs in personalized medicine, including applications for common diseases and risk stratification instruments for targeted prevention/intervention strategies. Not all of these applications may be extrapolated from the Caucasian experience to Latin American or other under-represented populations.
  • 1.4K
  • 04 Nov 2020
Topic Review
Tunneling Nanotubes
Tunneling nanotubes (TNTs) are recognized long membrane nanotubes connecting distance cells. In the last decade, growing evidence has shown that these subcellular structures mediate the specific transfer of cellular materials, pathogens, and electrical signals between cells. As intercellular bridges, they play a unique role in embryonic development, collective cell migration, injured cell recovery, cancer treatment resistance, and pathogen propagation. Although TNTs have been considered as potential drug targets for treatment, there is still a long way to go to translate the research findings into clinical practice.
  • 1.4K
  • 10 Mar 2021
Topic Review
Human Paraoxonase-2
PON1, PON2, and PON3 belong to a family of lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) involved in bacterial quorum-sensing signaling.
  • 1.4K
  • 28 Sep 2021
Topic Review
COVID-19 Serological Tests Performance
In only a few months after initial discovery in Wuhan, China, SARS-CoV-2 and the associated coronavirus disease 2019 (COVID-19) have become a global pandemic causing significant mortality and morbidity and implementation of strict isolation measures. In the absence of vaccines and effective therapeutics, reliable serological testing must be a key element of public health policy to control further spread of the disease and gradually remove quarantine measures. Serological diagnostic tests are being increasingly used to provide a broader understanding of COVID-19 incidence and to assess immunity status in the population. However, there are discrepancies between claimed and actual performance data for serological diagnostic tests on the market. In this study, we conducted a review of independent studies evaluating the performance of SARS-CoV-2 serological tests. We found significant variability in the accuracy of marketed tests and highlight several lab-based and point-of-care rapid serological tests with high levels of performance. The findings of this review highlight the need for ongoing independent evaluations of commercialized COVID-19 diagnostic tests.
  • 1.4K
  • 19 Feb 2021
Topic Review
Zinc Dyshomeostasis and Parkinson’s Disease
Zinc and other heavy metals have received considerable attention in neurodegenerative diseases because of their cytotoxicity. The role of zinc in the pathogenesis of PD is not straightforward because of its numerous and complex function. Both deficiency and excess of zinc have been incriminated in the development of the disease, though overwhelming evidence favor the later mechanism.
  • 1.4K
  • 20 May 2021
Topic Review
Cerebellar Ataxias
The terminology of cerebellar ataxias (CAs) embraces a ubiquitous deficit in 3 elemental domains: (a) limbs’ motor symptoms, (b) oculomotor symptoms, and (c) cognitive/emotional symptoms occurring in patients showing cerebellar dysfunction. Patients with CAs develop inaccuracy and clumsiness limb movements, characterized by dysmetria, tremor and adiadochokinesis. Posture is irregular and gait is unstable. Ocular movements lack accuracy. Cerebellar patients also show similar deficits in executive functions, linguistic processing, spatial cognition and affect regulation. Recent physiological studies have clarified that cerebellar outputs are modified by the release or facilitation of Purkinje cell-mediated inhibition on the cerebellar nucleus neurons. Thus, impairments in the formation of output signals elicit asthenia and adventitious movements, described by Holmes. These output signals are formed under controls of the internal forward model, embedded in the cerebellum. The deficits in the predictive computation for voluntary movements explains a range of characteristics accompanied by dysmetria. We argue that the impairments in the cerebellar outputs signals and the dysfunction in the internal forward model are fundamental mechanisms explaining the deficits in the 3 domains.
  • 1.4K
  • 02 Jul 2021
Topic Review
Hypophosphatasia: a Rare Bone Disease
Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5′-phosphate (PLP).
  • 1.4K
  • 10 May 2021
Topic Review
Vulvovaginal Candidosis
Vulvovaginal candidosis (VVC) is a frequently occurring infection of the lower female genital tract, mostly affecting immuno-competent women at childbearing age. Candida albicans is the most prevalent pathogenic yeast—apart from other non-albicans species—related to this fungal infection. Different virulence factors of C. albicans have been identified, which increase the risk of developing VVC. To initiate treatment and positively influence the disease course, fast and reliable diagnosis is crucial. In this narrative review, we cover the existing state of understanding of the epidemiology, pathogenesis and diagnosis of VVC. However, treatment recommendations should follow current guidelines.
  • 1.4K
  • 20 Nov 2020
Topic Review
CAR-T Cell
Adoptive cellular approaches utilizing chimeric antigen receptor T cells (CAR-T) targeting cancer-specific antigens would be a solution for circumventing the immune tolerance mechanisms. The immunotherapeutic regimen of CAR-T cell therapy has shown potential in the eradication of hematologic malignancies, and current clinical objectives maintain the equivalent efficacy in the treatment of solid tumors, including PCa. 
  • 1.4K
  • 20 Feb 2021
Topic Review
Duchenne Muscular Dystrophy
In Duchenne muscular dystrophy (DMD), the activation of proinflammatory and metabolic cellular pathways in skeletal muscle cells is an inherent characteristic. Synthetic glucocorticoid intake counteracts the majority of these mechanisms. However, glucocorticoids induce burdensome secondary effects, including hypertension, arrhythmias, hyperglycemia, osteoporosis, weight gain, growth delay, skin thinning, cushingoid appearance, and tissue-specific glucocorticoid resistance. Hence, lowering the glucocorticoid dosage could be beneficial for DMD patients. A more profound insight into the major cellular pathways that are stabilized after synthetic glucocorticoid administration in DMD is needed when searching for the molecules able to achieve similar pathway stabilization. This review provides a concise overview of the major anti-inflammatory pathways, as well as the metabolic effects of glucocorticoids in the skeletal muscle affected in DMD. The known drugs able to stabilize these pathways, and which could potentially be combined with glucocorticoid therapy as steroid-sparing agents, are described. This could create new opportunities for testing in DMD animal models and/or clinical trials, possibly leading to smaller glucocorticoids dosage regimens for DMD patients.
  • 1.4K
  • 10 Nov 2020
Topic Review
IFN-γ and Intracellular Protozoan Parasites
IFN-γ is an important cytokine in both innate and adaptive immune responses during intracellular parasite infections. Elevated levels of IFN-γ is detected in both experimental animals and human patients following intracellular protozoal infections. An extensive number of studies support a protective role for IFN-γ against the infection of intracellular protozoan parasites, including Plasmodium, Toxoplasma, Cryptosporidium, Trypanosoma, Leishmania, while a few studies also indicated that IFN-γ contributes to the pathogenesis of parasite infection.
  • 1.4K
  • 24 Feb 2023
Topic Review
SMARCB1 in the Pathobiology of Epithelioid Sarcoma
SMARCB1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1) is a key component of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes. Functional inactivation of SMARCB1 is the only recurrent genetic alteration reported in so far in Epithelioid Sarcoma (ES), a very rare and aggressive mesenchymal tumor of unclear origin and uncertain lineage characterized by a prevalent epithelioid morphology.
  • 1.4K
  • 13 Sep 2022
Topic Review
CDKs in Sarcoma
Sarcomas represent one of the most challenging tumor types to treat due to their diverse nature and our incomplete understanding of their underlying biology. Recent work suggests cyclin-dependent kinase (CDK) pathway activation is a powerful driver of sarcomagenesis. CDK proteins participate in numerous cellular processes required for normal cell function, but their dysregulation is a hallmark of many pathologies including cancer. The contributions and significance of aberrant CDK activity to sarcoma development, however, is only partly understood. Here, we describe what is known about CDK-related alterations in the most common subtypes of sarcoma and highlight areas that warrant further investigation. As disruptions in CDK pathways appear in most, if not all, subtypes of sarcoma, we discuss the history and value of pharmacologically targeting CDKs to combat these tumors. The goals of this review are to (1) assess the prevalence and importance of CDK pathway alterations in sarcomas, (2) highlight the gap in knowledge for certain CDKs in these tumors, and (3) provide insight into studies focused on CDK inhibition for sarcoma treatment. Overall, growing evidence demonstrates a crucial role for activated CDKs in sarcoma development and as important targets for sarcoma therapy.
  • 1.4K
  • 29 Oct 2020
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