Citrus fruit flavonoids as possible restorative providers A review

Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. click here TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.Microglia-mediated neuroinflammation is one of the key mechanisms involved in acute brain injury and chronic neurodegeneration. This study investigated the inhibitory effects of 2-hydroxy-4-methylbenzoic anhydride (HMA), a novel synthetic derivative of HTB (3-hydroxy-4-trifluoromethylbenzoic acid) on neuroinflammation and underlying mechanisms in activated microglia in vitro and an in vivo mouse model of Parkinson's disease (PD). In vitro studies revealed that HMA significantly inhibited lipopolysaccharide (LPS)-stimulated excessive release of nitric oxide (NO) in a concentration dependent manner. In addition, HMA significantly suppressed both inducible NO synthase and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in LPS-stimulated BV-2 microglia cells. Moreover, HMA significantly inhibited the proinflammatory cytokines such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in LPS-stimulated BV-2 microglial cells. Furthermore, mechanistic studies ensured that the potent anti-neuroinfl neuroinflammatory disorders, including PD.The novel COVID-19, detected in Wuhan, China, has reached almost every city across the globe, and researchers from many countries have used several epidemiologic models to describe the epidemic trends. In this context, it is also important to know the geographic extent of the infected population. Following this approach, a Gumpertz model was adapted with official data from the state of Hidalgo, Mexico, in order to estimate the people infected during this COVID-19 pandemic. We found, based on the adjusted data, the highest value in infected people according to official and theoretical data. Furthermore, using a geographical analysis based on geostatistical measures related to density of demographic and economic data, traffic level and geolocation, raster files were generated to estimate probability of coronavirus cases occurrence using the areas where the contagion may occur. We also distributed the maximum contagion obtained by the epidemic model, using these raster files, and a regression model to weight factors according their importance. Based on this estimated distribution, we found that most of the infected people were located in the southern border, a trend related to the economic strip in the southern part of Hidalgo State, associated with its vicinity to the Megacity of Mexico.Despite the prevalence of the common pharmaceutical ibuprofen (IBU) in water and sediments worldwide, the effects of IBU on plants are largely unknown. This study was designed to assess the ecotoxicological effects of emerging pharmaceutical pollutant IBU on plant growth and development in a series of toxicity experiments using cowpea (Vigna unguiculata). Plant growth parameters (morphological and physicochemical) were investigated under a series of IBU concentrations (0, 400, 800, 1200, 1600, 2000 ppm IBU). IBU exposure reduced the shoot and root lengths, fresh and dry weights, leaf area, and chlorophyll a and b, carotenoid, total chlorophyll, mineral (K and Mg), glutathione reductase, and soluble protein contents. Simultaneously, increases in Ca and Mn contents, sodium translocation from roots to shoots, H2O2, malondialdehyde, superoxide dismutase, catalase, ascorbate peroxidase, and IBU uptake were observed. The amount of bioaccumulated IBU varied between 7% and 8%. IBU was translocated from roots to shoots with a translocation factor of 3-16%. The IC50 values for biomass and plant length were 1253 and 1955 ppm IBU, respectively, which is much higher than the reported levels of IBU in the environment. This study demonstrates that cowpea plants develop several morphological and physicochemical adaptations to cope under ibuprofen stress; environmentally relevant concentrations of IBU are unlikely to produce negative impacts.Second skin is a topically applied, skin-conforming material that mimics human skin properties and bears potential cosmetic and e-skin applications. To successfully integrate with natural skin, characteristics such as color and skin features must be matched. In this work, we prepared bio-based skin-like films from cross-linked keratin/melanin films (KMFs), using a simple fabrication method and non-toxic materials. The films retained their stability in aqueous solutions, showed skin-like mechanical properties, and were homogenous and handleable, with non-granular surfaces and a notable cross-linked structure as determined by attenuated total reflection (ATR). In addition, the combination of keratin and melanin allowed for adjustable tones similar to those of natural human skin. Furthermore, KMFs showed light transmittance and UV-blocking (up to 99%) as a function of melanin content. Finally, keratin/melanin ink (KMI) was used to inkjet-print high-resolution images with natural skin pigmented features. The KMFs and KMI may offer advanced solutions as e-skin or cosmetics platforms.Multiple myeloma (MM) is a hematological malignancy with a poor prognosis while with a long and progressive outcome. To date, the therapeutic options are restricted to few drugs, including thalidomide or its derivates and autologous transplantation including stem-cell transplantation. More recently, the use of both proteasome inhibitors and monoclonal antibodies have been included in MM therapy, but the clinical results are still under evaluation. Unfortunately, death rates (within the 5-year overall survival rates) are still very high (45%), with no relevant improvement over the past 10 years. Here, we discuss data supporting a new therapeutic approach against MM, based on a common phenotype of tumor malignancies, which is the acidic microenvironment. Extracellular acidity drastically reduces the efficacy of both anti-tumor drugs and the immune reaction against tumors. Pre-clinical data have shown that anti-acidic drugs, such as proton pump inhibitors (PPIs), have a potent cytotoxic effect against human MM cells, thus supporting their use in the treatment of this malignancy. Here, we discuss also similarities between MM and type II diabetes mellitus (DM) with high risk of developing MM, suggesting that both anti-diabetic drugs and a hypocaloric diet may help in curing MM patients.Gravity in the head-to-toe direction, known as +Gz (G force), forces blood to pool in the lower body. Fighter pilots experience decreases in blood pressure when exposed to hypergravity in flight. Human centrifuge has been used to examine the G tolerance and anti-G straining maneuver (AGSM) techniques of military pilots. Some factors that may affect G tolerance have been reported but are still debated. The aim of this study was to investigate the physiological responses and anthropometric factors correlated with G tolerance. We retrospectively reviewed the training records of student pilots who underwent high G training. Variables were collected to examine their correlations with the outcome of 7.5G sustained for 15 s (7.5G profile). There were 873 trainees who underwent 7.5G profile training, 44 trainees (5.04%) could not sustain the test for 15 s. The group with a small heart rate (HR) increase (less than 10%) during the first 1-5 s of the 7.5G profile had a nearly ten-fold higher failing chance compared with the large HR increase group (adjusted odds ratio 9.91; 95% confidence interval 4.11-23.88). The chances of failure were inversely related to the HR increase percentage (p for trend less then 0.001). Factors, including body mass index, relaxed and straining G tolerance, and AGSM, were found to be negatively correlated with the outcome.The human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models.The bonded lingual retainer (BLR) is considered a favorable choice for retaining lower incisors' alignment post-orthodontic treatment; however, it may cause some unwanted effects such as inadvertent tooth movement and torque changes. These often result in gingival recession (Miller class III-type) with exposure of the root surface, which compromises the esthetics and hinders the comfort of the patient. Fifteen post-orthodontic patients presenting Miller class III-type recessions with BLR were examined. Two protocols were used the first included the removal of the BLR prior to surgery and the second included only a surgical approach. All patients underwent the same surgery of a modified tunnel double papilla procedure for root coverage. The gingival recession was measured using a dental probe before, and three to six months post-surgery. The average improvement in recession depth was significantly greater (p = 0.008) for the protocol that included removal of the BLR (4.0 ± 0.83 mm) with an improvement of 87.2% as compared to the second protocol that showed an improvement of 43.8% (1.88 ± 1.29 mm). Removing the BLR prior to surgery is beneficial for predictable root coverage in post-orthodontic Miller class III recessions.