Cancer is the second major threat to human society and one of the main challenges facing healthcare systems. One of the main problems of cancer care is the metastases of cancer cells that cause 90% of deaths due to cancer. Multiple molecular mechanisms are involved in cancer cell metastasis. Therefore, a better understanding of these molecular mechanisms is necessary for designing restrictive strategies against cancer cell metastasis. Accumulating data suggests that MicroRNAs (miRNAs) are involved in metastasis and invasion of human tumors through regulating multiple genes expression levels that are involved in molecular mechanisms of metastasis. The goal of this review is to present the molecular pathways by which the miR 200 family manifests its effects on EMT, cancer stem cells, angiogenesis, anoikis, and the effects of tumor cell metastases.
MethodsA detailed literature search was conducted to find information about the role of the miR-200 family in the processes involved in metastasis in various databases.
ResultsNumerous lines of evidence revealed an association between the mir-200 family and metastasis of human tumors by impressing processes such as cancer stem cells, EMT, angiogenesis, and anoikis.
ConclusionsUnderstanding the molecular mechanisms associated with metastasis in which the miR-200 family is involved can be effective in treating metastatic cancers.
Graphic abstractThe present work aimed to investigate the antioxidant, anti-inflammatory and wound healing potential of ethyl acetate fraction from Bauhinia ungulata L. (FABU) on in vitro and in vivo models. Wound healing assay using human lung adenocarcinoma A549 cell line was employed to evaluate the ability of FABU in modulating cell migration. In addition, a surgical wound model in C57BL/6 mice was used to study the healing potential of FABU incorporated into gel carbomer 940 (Carbopol®). Evaluation of lipid peroxidation, inflammatory and anti-inflammatory mediator gene expression, rate of wound closure, and histological analysis were done. FABU significantly reduced the gap area in in vitro wound healing assay, 24 h after treatment. In the animal model, FABU at 0.5% topically applied once-daily for 5 days to the surgical wounds significantly reduced the lesion area. Moreover, it significantly decreased the levels of lipid peroxidation in the lesions and decreased the relative gene expression levels of IL-1β and TNF-α in the injured region. In conclusion, our study suggests that Bauhinia ungulata can effectively promote the wound healing, probably by regulating the inflammatory environment during the early stages of the process.
Graphic abstractA role of Retinol Binding Protein-4 (RBP4) in insulin resistance is widely studied. However, there is paucity of information on its receptor viz., Stimulated by Retinoic Acid-6 (STRA6) with insulin resistance. To address this, we investigated the regulation of RBP4/STRA6 expression in 3T3-L1 adipocytes exposed to glucolipotoxicity (GLT) and in visceral adipose tissue (VAT) from high fat diet (HFD) fed insulin-resistant rats. 3T3-L1 adipocytes were subjected to GLT and other experimental maneuvers with and without vildagliptin or metformin. Real-time PCR and western-blot experiments were performed to analyze RBP4, STRA6, PPARγ gene and protein expression. Adipored staining and glucose uptake assay were performed to evaluate lipid and glucose metabolism. Oral glucose tolerance test (OGTT) and Insulin Tolerance Test (ITT) were performed to determine the extent of insulin resistance in HFD fed male Wistar rats. Total serum RBP4 was measured by quantitative sandwich enzyme-linked immunosorbent assay kit. Adipocytes under GLT exhibited significantly increased RBP4/STRA6 expressions and decreased insulin sensitivity/glucose uptake. Vildagliptin and metformin not only restored the above but also decreased the expression of IL-6, NFκB, SOCS-3 along with lipid accumulation. Furthermore, HFD fed rats exhibited significantly increased serum levels of RBP4 along with VAT expression of RBP4, STRA6, PPARγ, IL-6. These molecules were significantly altered by the vildagliptin/ metformin treatment. We conclude that RBP4/STRA6 pathway is primarily involved in mediating inflammation and insulin resistance in adipocytes and visceral adipose tissues under glucolipotoxicity and in insulin resistant rats.
Graphic abstractIn utero hyperglycemia has consequences on future outcomes in the offsprings. We had earlier shown that in utero hyperglycemia impacts proteoglycans/glycosaminoglycans, one of the key molecules involved in brain development. Hypothalamic HSPGs such as syndecan-1 and syndecan-3 are well known for their involvement in feeding behavior. Therefore, studies were carried out to determine the effect of maternal hyperglycemia on the expression of HSPGs in the hypothalamus of offspring brain. Results revealed increased protein abundance of Syndecan-1 and -3 as well as glypican-1 in postnatal adults from hyperglycemic mothers. This was associated with increased hyperphagia and increased expression of Neuropeptide Y. These results indicate the likely consequences on offsprings exposed to in utero hyperglycemia on its growth.
Graphical abstractIt is considered a significant challenge to understand the neuronal cell death mechanisms with a suitable cure for neurodegenerative disorders in the coming years. Calpains are one of the best-considered “cysteine proteases activated” in brain disorders. Calpain is an important marker and mediator in the pathophysiology of neurodegeneration. Calpain activation being the essential neurodegenerative factor causing apoptotic machinery activation, it is crucial to develop reliable and effective approaches to prevent calpain-mediated apoptosis in degenerating neurons. It has been recently seen that the “inhibition of calpain activation” has appeared as a possible therapeutic target for managing neurodegenerative diseases. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was conducted. The present article reviews the basic pathobiology and role of selective calpain inhibitors used in various neurodegenerative diseases as a therapeutic target.
Graphical AbstractPoor quality and quantity of sleep are very common in elderly people throughout the world. Growing evidence has suggested that sleep disturbances could accelerate the process of neurodegeneration. Recent reports have shown a positive correlation between sleep deprivation and amyloid-β (Aβ)/tau aggregation in the brain of Alzheimer’s patients. Glial cells have long been implicated in the progression of Alzheimer’s disease (AD) and recent findings have also suggested their role in regulating sleep homeostasis. However, how glial cells control the sleep–wake balance and exactly how disturbed sleep may act as a trigger for Alzheimer’s or other neurological disorders have recently gotten attention. In an attempt to connect the dots, the present review has highlighted the role of glia-derived sleep regulatory molecules in AD pathogenesis.
Graphical AbstractRole of glia in sleep disturbance and Alzheimer’s progression.
Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.
Graphic abstractBoron is an important element for plants, humans, and animals in limited amounts. However, excess amounts can cause adverse effects in both humans and plants, necessitating its removal from certain systems. Boron compounds are used in many industrial applications, including in developing sectors like alternative energy technology; as a result, the need for this element is increasing and industries are looking towards boron recovery for the sustained use of this element in their products. While the literature on boron removal strategies is abundant, there is a relative lack of studies on boron recovery, with no review papers having yet addressed this topic. In this review, both boron removal and recovery techniques involving conventional approaches and membrane processes are examined to juxtapose the states of the science in these two related—and increasingly important—processes.
Graphical abstractThe increased phenomenon of antimicrobial resistance and the slow pace of development of new antibiotics are at the base of a global health concern regarding microbial infections. Antibiotic resistance kills an estimated 700,000 people each year worldwide, and this number is expected to increase dramatically if efforts are not made to develop new drugs or alternative containment strategies. Increased vaccination coverage, improved sanitation or sustained implementation of infection control measures are among the possible areas of action. Indeed, vaccination is one of the most effective tools of preventing infections. Starting from 1970s polysaccharide-based vaccines against Meningococcus, Pneumococcus and Haemophilus influenzae type b have been licensed, and provided effective protection for population. However, the development of safe and effective vaccines for infectious diseases with broad coverage remains a major challenge in global public health. In this scenario, nanosystems are receiving attention as alternative delivery systems to improve vaccine efficacy and immunogenicity. In this report, we provide an overview of current applications of glyconanomaterials as alternative platforms in the development of new vaccine candidates. In particular, we will focus on nanoparticle platforms, used to induce the activation of the immune system through the multivalent-displacement of saccharide antigens.
Graphical abstractNeuroblastoma is the most common extracranial solid tumour in childhood, originated from cells of the neural crest during the development of the Sympathetic Nervous System. Retinoids are vitamin-A derived differentiating agents utilised to avoid disease resurgence in high-risk neuroblastoma treatment. Several studies indicate that hypoxia—a common feature of the tumoural environment—is a key player in cell differentiation and proliferation. Hypoxia leads to the accumulation of the hypoxia-inducible factor-1α (HIF-1α). This work aims to investigate the effects of the selective inhibition of HIF-1α on the differentiation induced by retinoic acid in human neuroblastoma cells from the SH-SY5Y lineage to clarify its role in cell differentiation. Our results indicate that HIF-1α inhibition impairs RA-induced differentiation by reducing neuron-like phenotype and diminished immunolabeling and expression of differentiation markers.
Graphic AbstractHIF1A is involved in Retinoic Acid (RA) induced differentiation in SH-SY5Y neuroblastoma cells. siRNA HIF1A gene silencing leads to a weaker response to RA, demonstrated by changes in the neuro-like phenotype and diminished expression of differentiation markers.
Mitochondrial-associated endoplasmic reticulum (ER) membranes (MAMs) play a key role in several physiological functions, including calcium ion (Ca2+) transfer and autophagy; however, the molecular mechanism controlling this interaction in cadmium (Cd)-induced neurotoxicity is unknown. This study shows that Cd induces alterations in MAMs and mitochondrial Ca2+ levels in PC12 cells and primary neurons. Ablation or silencing of mitofusin 2 (Mfn2) in PC12 cells or primary neurons blocks the colocalization of ER and mitochondria while reducing the efficiency of mitochondrial Ca2+ uptake. Moreover, Mfn2 defects reduce interactions or colocalization between GRP75 and VDAC1. Interestingly, the enhancement of autophagic protein levels, colocalization of LC3 and Lamp2, and GFP-LC3 puncta induced by Cd decreased in Mfn2?/? or Grp75?/? PC12 cells and Mfn2- or Grp75-silenced primary neurons. Notably, the specific Ca2+ uniporter inhibitor RuR blocked both mitochondrial Ca2+ uptake and autophagy induced by Cd. Finally, this study proves that the mechanism by which IP3R-Grp75-VDAC1 tethers in MAMs is associated with the regulation of autophagy by Mfn2 and involves their role in mediating mitochondrial Ca2+ uptake from ER stores. These results give new evidence into the organelle metabolic process by demonstrating that Ca2+ transport between ER-mitochondria is important in autophagosome formation in Cd-induced neurodegeneration.
Graphical abstractDrusen deposition on sub-retinal pigment epithelium is the causal factor for age-related macular degeneration for the old-aged individuals. These deposits contain hydroxyapatite–cholesterol spherules on which several proteins and lipids accumulate to cover the retina and choroid, causing blurred vision and blindness. Amyloid-β, the known culprit in Alzheimer’s disease, is one among the few major proteins known to occur in these deposits. In the present article, we report preliminary analyses of interactions between amyloid-β and hydroxyapatite–cholesterol composites using Thioflavin-T binding kinetics, solid-state NMR and transmission electron microscopy (TEM). Thioflavin-T fluorescence kinetics shows that amyloid-β (1–42) aggregates only under certain conditions of concentration of cholesterol in the hydroxyapatite–cholesterol composites prepared by two different methods. These results were confirmed by 1D 13C CPMAS solid-state NMR. TEM imaging revealed that there is an exposure of the cholesterol surface in the composites prepared by sonication method. These imaging experiments explain the dependence of aggregation kinetics on the exposure and availability of cholesterol surface in the composites to a certain extent.
Graphic AbstractDysfunction of the gastrointestinal tract (GIT) is one of the most common non-motor symptom of Parkinson’s Disease (PD). Pathological processes causing PD were suggested to initiate in the enteric nervous system (ENS) and proceed to the central nervous system (CNS). There are studies showing that low-carbohydrate ketogenic diets can improve motor symptoms of PD. Caprylic acid (C8) is the principal fatty acid component of the medium-chain triglycerides in the ketogenic diets. In this study, we aimed to evaluate the effects of caprylic acid, in neurotoxin exposed zebrafish focusing on the relationship between intestinal and brain oxidative stress and inflammation.
MethodsAdult zebrafish were exposed to rotenone (5 μg/L) (R group) and caprylic acid (20 and 60 mg/mL) (L?+?HDCA and R?+?HDCA groups) for 30 days. At the end of 30 days locomotor activities were determined. Levels of lipid peroxidation (LPO), nitric oxide, glutathione and superoxide dismutase and glutathione S-transferase activities were determined by spectrophotometric methods and gene expressions of tnf?, il1, il6, il21, ifn? and bdnf were evaluated by RT-PCR in the brain and intestinal tissues of zebrafish.
ResultsCaprylic acid ameliorated LPO, NO, SOD and the expressions of tnf?, il1, il6, il21, ifn? and bdnf in brain and intestines. Locomotor activities were only ameliorated in high dose R?+?HDCA group.
ConclusionsCaprylic acid ameliorated the neurotoxin-induced oxidative stress and inflammation both in the brain and intestines and enhanced locomotor activity in zebrafish.
Graphical abstractThis article presents a machine learning workflow allowing to construct spectrophotometric equations predicting nitrate and nitrite concentrations within microalgae culture samples. First, numerous samples with various nitrate and nitrite concentrations (in mixture or separated) were drawn from cultures. Their UV absorbance spectra were recorded with a tabletop spectrophotometer before being analyzed using ion chromatography. Then, the data collected were used to construct a machine leaning model based on partial least square regression. From a practical perspective, the best model involves 3 wavelengths to quantify both nitrate and nitrite within the samples. The proposed equations can readily be used (LoQ of 0.5 mg L??1, uncertainty of ± 10%). They greatly shorten the time to obtain sample nitrate and nitrite concentrations compared to ion chromatography while retaining adequate accuracy. Furthermore, the workflow is presented step-wise, with emphasis on relevant details so that other scholars may deploy in their own laboratory to best suit their own needs. Finally, the data and source files are made available in an online repository.
Model generation workflow and associated data management.
The mushrooms have contributed to the development of active ingredients of fundamental importance in the field of pharmaceutical chemistry as well as of important tools in human and animal health, nutrition, and functional food. This review considers studies on the beneficial effects of medicinal mushrooms on the nutrition and health of humans and farm animals. An overview of the chemical structure and composition of mycochemicals is presented in this review with particular reference to phenolic compounds, triterpenoids and sterols, fatty acids and lipids, polysaccharides, proteins, peptides, and lectins. The nutritional value and chemical composition of wild and cultivated mushrooms in Italy is also the subject of this review which also deals with mushrooms as nutraceuticals and the use of mushrooms in functional foods. The nutraceutical benefits of UV irradiation of cultivated species of basidiomycetes to generate high amounts of vitamin D2 is also highlighted and the ability of the muhsrooms to inhibit glycation is analyzed. Finally, attention is paid to studies on bioactivities of some Italian wild and cultivated mushrooms with particular reference to species belonging to the genus Pleurotus. The review highlights the potential of medicinal mushrooms in the production of mycochemicals that represent a source of drugs, nutraceutical, and functional food.
Graphic abstractIn this paper, we study the postcranial morphology (humerus, ulna, innominate, femur, tibia, astragalus, navicular, and metatarsal III) of Neoepiblema, a giant Late Miocene South American rodent, searching for evidence about its paleobiology based on unpublished specimens from Solimões Formation (Upper Miocene, Brazil). The study includes a morphofunctional analysis of the postcranial bones and a comparison with extant and extinct rodents, especially Phoberomys. The morphofunctional analysis of the postcranial bones suggests that Neoepiblema (as well as Phoberomys) would have a crouched forelimb that was not fully extended, with powerful pectoral and triceps musculature, and able to produce movements of pronation/supination and possibly with a hand able to grasp. The combination of characters of the innominate bone, femur, and tibia indicates a predominance of parasagittal movements and a thigh with powerful musculature used during propulsion. In sum, the analyzed postcranial features are consistent with the limb morphology of ambulatory rodents, but with faculty to dig or swim. The sedimentary evidence of the localities in which fossils of neoepiblemids have been found suggests that these rodents lived in wet and water-related environments (near swamps, lakes, and/or rivers).
Graphical abstract