The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them ...share the condition of an "inflammatory disorder", with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system-microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.
Macrophages are a type of immune cell distributed throughout all tissues of an organism. Allograft inflammatory factor 1 (AIF1) is a calcium-binding protein linked to the activation of macrophages. ...AIF1 is a key intracellular signaling molecule that participates in phagocytosis, membrane ruffling and F-actin polymerization. Moreover, it has several cell type-specific functions. AIF1 plays important roles in the development of several diseases: kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases and neurological disorders, and in transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases.
Since the worldwide COVID-19 pandemic was declared a year ago, the search for vaccines has become the top priority in order to restore normalcy after 2.5 million deaths worldwide, overloaded sanitary ...systems, and a huge economic burden. Vaccine development has represented a step towards the desired herd immunity in a short period of time, owing to a high level of investment, the focus of researchers, and the urge for the authorization of the faster administration of vaccines. Nevertheless, this objective may only be achieved by pursuing effective strategies and policies in various countries worldwide. In the present review, some aspects involved in accomplishing a successful vaccination program are addressed, in addition to the importance of vaccination in a pandemic in the face of unwillingness, conspiracy theories, or a lack of information among the public. Moreover, we provide some updated points related to the landscape of the clinical development of vaccine candidates, specifically, the top five vaccines that are already being assessed in Phase IV clinical trials (BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, and CoronaVac).
The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and ...bidirectional communication between gut microbiota and the host, conforming to a unique entity known as "holobiont". Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood-brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered microbiota-gut-brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.
The placenta is a central structure in pregnancy and has pleiotropic functions. This organ grows incredibly rapidly during this period, acting as a mastermind behind different fetal and maternal ...processes. The relevance of the placenta extends far beyond the pregnancy, being crucial for fetal programming before birth. Having integrative knowledge of this maternofetal structure helps significantly in understanding the development of pregnancy either in a proper or pathophysiological context. Thus, the aim of this review is to summarize the main features of the placenta, with a special focus on its early development, cytoarchitecture, immunology, and functions in non-pathological conditions. In contraposition, the role of the placenta is examined in preeclampsia, a worrisome hypertensive disorder of pregnancy, in order to describe the pathophysiological implications of the placenta in this disease. Likewise, dysfunction of the placenta in fetal growth restriction, a major consequence of preeclampsia, is also discussed, emphasizing the potential clinical strategies derived. Finally, the emerging role of the placenta in maternal chronic venous disease either as a causative agent or as a consequence of the disease is equally treated.
Chronic venous disease (CVD) is a common vascular disorder characterized by increased venous hypertension and insufficient venous return from the lower limbs. Pregnancy is a high-risk situation for ...developing CVD. Approximately a third of the women will develop this condition during pregnancy, and similarly to arterial hypertensive disorders, previous evidence has described a plethora of alterations in placental structure and function in women with pregnancy-induced CVD. It is widely known that arterial-induced placenta dysfunction is accompanied by an important immune system alteration along with increased inflammatory markers, which may provide detrimental consequences for the women and their offspring. However, to our knowledge, there are still no data collected regarding cytokine profiling in women with pregnancy-induced CVD. Thus, the aim of the present work was to examine cytokine signatures in the serum of pregnant women (PW) with CVD and their newborns (NB). This study was conducted through a multiplex technique in 62 PW with pregnancy-induced CVD in comparison to 52 PW without CVD (HC) as well as their NB. Our results show significant alterations in a broad spectrum of inflammatory cytokines (IL-6, IL-12, TNF-α, IL-10, IL-13, IL-2, IL-7, IFN-γ, IL-4, IL-5, IL-21, IL-23, GM-CSF, chemokines (fractalkine), MIP-3α, and MIP-1β). Overall, we demonstrate that pregnancy-induced CVD is associated with a proinflammatory environment, therefore highlighting the potentially alarming consequences of this condition for maternal and fetal wellbeing.
Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: ...prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundless possibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented. Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectious diseases and many other health issues.
Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative ...symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations.
In recent years, the importance of epigenetic markers in the carcinogenesis of different malignant neoplasms has been demonstrated, also demonstrating their utility for understanding metastatic ...spread and tumor progression in cancer patients. Among the different biomarkers, microRNAs represent a set of non-coding RNAs that regulate gene expression, having been involved in a wide variety of neoplasia acting in different oncogenic pathways. Both the overexpression and downregulation of microRNAs represent a complex interaction with various genes whose ultimate consequence is increased cell proliferation, tumor invasion and interaction with various driver markers. It should be noted that in current clinical practice, even though the combination of different microRNAs has been shown to be useful by different authors at diagnostic and prognostic levels, there are no diagnostic kits that can be used for the initial approach or to assess recurrences of oncological diseases. Previous works have cited microRNAs as having a critical role in several carcinogenic mechanisms, ranging from cell cycle alterations to angiogenesis and mechanisms of distant metastatic dissemination. Indeed, the overexpression or downregulation of specific microRNAs seem to be tightly involved in the modulation of various components related to these processes. For instance, cyclins and cyclin-dependent kinases, transcription factors, signaling molecules and angiogenic/antiangiogenic products, among others, have been recognized as specific targets of microRNAs in different types of cancer. Therefore, the purpose of this article is to describe the main implications of different microRNAs in cell cycle alterations, metastasis and angiogenesis, trying to summarize their involvement in carcinogenesis.
Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in ...children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations.
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