19 research outputs found
Tumor-induced neurogenesis and immune evasion as targets of innovative anti-cancer therapies
Normal cells are hijacked by cancer cells forming together heterogeneous tumor masses immersed in aberrant communication circuits that facilitate tumor growth and dissemination. Besides the well characterized angiogenic effect of some tumor-derived factors; others, such as BDNF, recruit peripheral nerves and leukocytes. The neurogenic switch, activated by tumor-derived neurotrophins and extracellular vesicles, attracts adjacent peripheral fibers (autonomic/sensorial) and neural progenitor cells.
Strikingly, tumor-associated nerve fibers can guide cancer cell dissemination. Moreover, IL-1β, CCL2, PGE2, among other chemotactic factors, attract natural immunosuppressive cells, including T regulatory (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, to the tumor microenvironment. These leukocytes further exacerbate the aberrant communication circuit releasing factors with neurogenic effect. Furthermore, cancer cells directly evade immune surveillance and the antitumoral actions of natural
killer cells by activating immunosuppressive mechanisms elicited by heterophilic complexes, joining cancer and immune cells, formed by PD-L1/PD1 and CD80/CTLA-4 plasma membrane proteins. Altogether, nervous and immune cells, together with fibroblasts, endothelial, and bone-marrow-derived cells, promote tumor growth and enhance the metastatic properties of cancer cells. Inspired by the demonstrated, but restricted, power of anti-angiogenic and immune cell-based therapies, preclinical studies are focusing on
strategies aimed to inhibit tumor-induced neurogenesis. Here we discuss the potential of anti-neurogenesis and, considering the interplay between nervous and immune systems, we also focus on anti-immunosuppression-based therapies. Small molecules, antibodies and immune cells are being considered as therapeutic agents, aimed to prevent cancer cell communication with neurons and leukocytes, targeting chemotactic and neurotransmitter signaling pathways linked to perineural invasion and metastasis
Medicinal Plant Extracts and Their Use As Wound Closure Inducing Agents
Skin insult and damage start a complex healing process that involves a myriad of coordinated reactions at both the cellular and molecular level occurring simultaneously. These processes can be divided into that of cell migration and tissue remodeling of the wound. In addition, it is well known that deep wounds that derive from surgical procedures need a multidisciplinary approach to have a successful wound healing process. Recently, there has been a renowned interest in the identification of active compounds derived from ornamental, edible, and wild plants being used in the cosmetic and skin product industry. Recent reports suggest that active components of several plants such as Propolis and Aloe vera could be used
to induce the process of wound healing and tissue regeneration and reducing therefore the time to complete wound closure.
Other plant species such as Achillea millefolium or Salvia officinalis have anti-inflammatory properties and promote cellular proliferation contributing to faster tissue regeneration. It has been described that Malva sylvestris influences the formation of fibrosis-free granulation tissue in the skin. Recent observations suggest that Casearia sylvestris induces the angiogenic process. These effects have been evaluated in cell lines, different animal models, and some in randomized clinical trials. In this review we summarize the evidence of plant extracts and their active components (when known) in the acceleration of the wound closure process and tissue repair
Las flores de hibiscus sabdariffa y sus beneficios a la salud: una revisión de sus efectos cardiometabólicos y la relación con su composición de antocianinas
Algunos fitoquímicos son tóxicos para otros organismos, siendo éste un mecanismo de defensa contra factores estresores del medio ambiente. La hipótesis de la xenohormesis establece que dosis bajas de estas moléculas activan vías de señalización celular adaptativas que mejoran la salud. Reportes científicos señalan propiedades de las antocianinas de Hibiscus sabdariffa (HS) para tratar inflamación, hiperglucemia, hipertensión e hiperlipidemia, todos factores de riesgo para enfermedad cardiovascular. Esta revisión expone resultados en modelos celulares y animales, y estudios clínicos sobre las propiedades funcionales de las antocianinas de HS. La poca cantidad de estos compuestos en la planta hace que el consumo en la dieta de los humanos sea bajo, y su biodisponibilidad limitada. En la revisión se abordan procedimientos de extracción y enriquecimiento; así como estrategias para mejorar su estabilidad y biodisponibilidad. Finalmente se mencionan propuestas de formulaciones a base de extractos de HS en sistemas micro y nanoparticulados
Lipid Metabolism Alterations in a Rat Model of Chronic and Intergenerational Exposure to Arsenic
Chronic exposure to arsenic (As), whether directly through the consumption of contaminated drinking water or indirectly through the daily intake of As-contaminated food, is a health threat for more than 150 million people worldwide. Epidemiological studies found an association between chronic consumption of As and several pathologies, the most common being cancer-related disorders. However, As consumption has also been associated with metabolic disorders that could lead to diverse pathologies, suchas type 2 diabetes mellitus, nonalcoholic fatty liver disease, and obesity. Here, we used ultra-performance liquid chromatography
(UPLC) coupled to electrospray ionization/quadrupole time-of-flight mass spectrometry (ESI-QToF) to assess the effect of chronic intergenerational As exposure on the lipid metabolism profiles of serum from 4-month-old Wistar rats exposed to As prenatally and also during early life in drinking water (3 ppm). Significant differences in the levels of certain identified lyso-phospholipids, phosphatidylcholines, and triglycerides were found between the exposed rats and the control groups, as well as between the sexes. Significantly increased lipid oxidation determined by the malondialdehyde (MDA) method was found in exposed rats compared with controls. Chronic intergenerational As exposure alters the rat lipidome, increases lipid oxidation, and
dysregulates metabolic pathways, the factors associated with the chronic inflammation present in different diseases associated with chronic exposure to As (i.e., keratosis, Bowen’s disease, and kidney, liver, bladder, and lung cancer)
Myeloid-Derived Suppressor Cells Show Different Frequencies in Diabetics and Subjects with Arterial Hypertension
Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension.
Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics.
Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-β, according to an intracellular detection) is higher in patients with DM2 (P < 0:05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P < 0:05). Also, a negative correlation between the frequency of CD15+CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-β and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have anincreased concentration of IL-5
Persistence of COVID-19 Symptoms after Recovery in Mexican Population
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the
coronavirus disease (COVID-19), a highly contagious infectious disease that has caused many deaths
worldwide. Despite global efforts, it continues to cause great losses, and leaving multiple unknowns
that we must resolve in order to face the pandemic more effectively. One of the questions that has
arisen recently is what happens, after recovering from COVID-19. For this reason, the objective of
this study is to identify the risk of presenting persistent symptoms in recovered from COVID-19.
This case-control study was conducted in one state of Mexico. Initially the data were obtained
from the participants, through a questionnaire about symptoms that they had at the moment of the
interview. Initially were captured the collected data, to make a dataset. After the pre-processed using
the R project tool to eliminate outliers or missing data. Obtained finally a total of 219 participants,
141 recovered and 78 controls. It was used confidence level of 90% and a margin of error of 7%.
From results it was obtained that all symptoms have an associated risk in those recovered. The relative
risk of the selected symptoms in the recovered patients goes from 3 to 22 times, being infinite for the
case of dyspnea, due to the fact that there is no control that presents this symptom at the moment of
the interview, followed by the nausea and the anosmia with a RR of 8.5. Therefore, public health
strategies must be rethought, to treat or rehabilitate, avoiding chronic problems in patients recovered
from COVID-19
Innate Immunity Alterations in Type 2 Diabetes Mellitus: Understanding Infection Susceptibility
Diabetes is a chronic disease characterized by marked alterations in the
metabolism of glucose and by high concentrations of glucose in the blood due to a
decreased insulin production or resistance to the action of this hormone in peripheral
tissues. The International Diabetes Federation estimates a global incidence of diabetes
of about 10% in the adult population (20 - 79 years old), some 430 million cases
reported worldwide in 2018. It is well documented that people with diabetes have a
higher susceptibility to infectious diseases and therefore show higher morbidity and
mortality compared to the non-diabetic population. Given that the innate immune
response plays a fundamental role in protecting against invading pathogens through a
myriad of humoral and cellular mechanisms, the present work makes a comprehensive
review of the innate immune alterations in patients with type 2 diabetes mellitus (T2D) as
well as a brief description of the molecular events leading or associated to such
conditions. We show that in these patients a compromised innate immune response
increases susceptibility to infections
Correction: Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients.
[This corrects the article DOI: 10.1371/journal.pone.0150900.]