Acute pancreatitis (AP) is a severe inflammation of the pancreas presented with sudden onset and severe abdominal pain with a high morbidity and mortality rate, if accompanied by severe local and ...systemic complications. Numerous studies have been published about the pathogenesis of AP; however, the precise mechanism behind this pathology remains unclear. Extensive research conducted over the last decades has demonstrated that the first 24 h after symptom onset are critical for the identification of patients who are at risk of developing complications or death. The identification of these subgroups of patients is crucial in order to start an aggressive approach to prevent mortality. In this sense and to avoid unnecessary overtreatment, thereby reducing the financial implications, the proper identification of mild disease is also important and necessary. A large number of multifactorial scoring systems and biochemical markers are described to predict the severity. Despite recent progress in understanding the pathophysiology of AP, more research is needed to enable a faster and more accurate prediction of severe AP. This review provides an overview of the available multifactorial scoring systems and biochemical markers for predicting severe AP with a special focus on their advantages and limitations.
Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the ...effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.
Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as ...well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.
Drug development strategy: Re and 99mTc tricarbonyl complexes with a pyridostatin moiety as a G4‐binding motif have been obtained through a post‐conjugation strategy using Pz‐COOH‐M. Metalation was ...found to enhance the complexes’ cytotoxicity in two cancer cell lines; the 99mTc congener was used to study binding and internalization. Possible uses of the complexes for DNA‐interaction, cell and biodistribution studies are illustrated. More information can be found in the Research Article by E. Palma, A. Paulo and co‐workers (DOI: 10.1002/chem.202400285).
Objectives
To compare the treatments used to treat dentin hypersensitivity (DH), based on its efficacy and effect duration.
Methods
Medline/PubMed, Cochrane Library, EMBASE and ClinicalTrials were ...searched for articles published between 1 January 2008 and 14 November 2018, in English, Portuguese or Spanish, reporting clinical trials, completed and with results. This systematic review protocol was registered in PROSPERO, number CRD42019121986.
Results
Seventy‐four randomised clinical trials were included in the systematic review, reporting patients from 16 to 65 years old, with a clinical diagnosis of DH, that evaluate the efficacy of a desensitising product, compared to pre‐treatment, used the evaporative method stimulation and the visual analogue scale. These studies evaluated 5366 patients and at least 9167 teeth. Seven follow‐up periods were considered corresponding to an immediate, medium or long‐time effect. Sixty‐six studies were included in the quantitative synthesis. Glutaraldehyde with HEMA, glass ionomer cements and Laser present significant immediate (until 7 days) DH reduction. Medium‐term (until 1 month) reduction was observed in stannous fluoride, glutaraldehyde with HEMA, hydroxyapatite, glass ionomer cements and Laser groups. Finally, long‐term significant reduction was seen at potassium nitrate, arginine, glutaraldehyde with HEMA, hydroxyapatite, adhesive systems, glass ionomer cements and LASER.
Conclusions
All active ingredients show efficacy in DH reduction in different follow‐up times. Only in‐office treatments are effective in immediate DH reduction, maintaining its efficacy over time. For long‐time effects, at‐home treatments can also be used. More standardised evaluation protocols should be implemented to increase the robustly of the results.
The main goal of this work was to elucidate the potential relevance of (radio)metal chelates of 99mTc and Re targeting G‐quadruplex structures for the design of new tools for cancer theranostics. ...99mTc provides the complexes with the ability to perform single‐photon‐emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural 99mTc(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl‐diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4‐binding motif. The interaction of the PDF‐Pz‐Re (8) complex with different G4‐forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET‐melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4‐structures from different DNA or RNA sequences, namely those present on the SRC proto‐oncogene and telomeric RNA (TERRA sequence). PDF‐Pz‐Re (8) showed low to moderate cytotoxicity in PC3 and MCF‐7 cancer cell lines, as typically observed for G4‐binders. Biodistribution studies of the congener PDF‐Pz‐99mTc (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability.
New (Radio)metalated G4 binders: Re(I) and 99mTc(I) complexes carrying pyridostatin derivatives for the targeting of G‐quadruplex structures. The Re complex can bind to G4 DNA and RNA with selectivity over double‐stranded DNA, exhibiting cytotoxic activity in MCF‐7 human breast cancer and PC3 human prostate cancer cell lines. The 99mTc congener is stable in vivo with a fast blood clearance in normal mice.
A new therapy based on atmospheric plasma, the fourth state of matter, has raised the medical community's attention by circumventing many undesirable effects of old anticancer treatments. This work ...aimed to evaluate the effect, selectivity, and mechanisms of action of cold atmospheric plasma (CAP) in human retinoblastoma cells.
An electronic device was designed to generate CAP in the open air, 2 mm above seeded cell cultures. Three approaches were performed: direct use of CAP, plasma-activated media (PAM), and conditioned media (CM). Timely-resolved output voltage measurement, emission spectroscopy, and quantification of reactive species (RS) of PAM were performed. To evaluate cytotoxicity and selectivity, similarly treated Y79, fibroblasts HFF1, and retinal RPE-D407 cells were assessed.
After 60 s of direct CAP treatment, the metabolic activity of retinoblastoma cells decreased more than 50%, mainly due to apoptosis, while HFF1 and RPE-D407 remained viable. Similar results were obtained with indirect treatment (PAM and CM). Cell survival was reduced, and cells accumulated in S and G2/M phases; however, no DNA strand breaks were detected. Regarding RS, plasma increased extracellular and intracellular concentrations of peroxides and nitric oxide, despite glutathione activation and lack of success in reverting cytotoxicity with some RS inhibitors. RS increase comes in two timely distant waves, the first one originating from the plasma itself with secondary solubilization and passive diffusion, the second wave deriving from the mitochondrion. The addition of low doses of carboplatin to CAP-treated cells resulted in a significant increase in cytotoxicity compared with either regimen alone. Additionally, maximal antiangiogenic effects were obtained with 60 s of plasma exposure.
Direct and indirect treatment with CAP might be a selective therapy with the potential to target tumour cells and supporting the microenvironment.
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•Plasma selectively decreases retinoblastoma cells viability and long-term survival.•Plasma induced apoptosis and cell cycle arrest without genotoxicity.•Plasma induced a biphasic generation of free nitroxidative radicals.•Mitochondrial ROS-induced ROS release may explain a second wave of radicals.•Plasma exposure goes beyond cancer cells displaying antiangiogenic effects.
Cell-based assays, conducted on monolayer (2D) cultured cells, are an unquestionably valuable tool for biomedical research. However, three-dimensional (3D) cell culture models have gained relevance ...over the last few years due to the advantages of better mimicking the microenvironment and tissue microarchitecture in vivo. Recent magnetic-based 3D (m3D) cell culture systems can be used for this purpose. These systems are based on exposing magnetized cells to magnetic fields by levitation, bioprinting, or ring formation to promote cell aggregation into 3D structures. However, the successful development of these structures is dependent on several methodological characteristics and can be applied to mimic different human tissues. Thus, a systematic review was performed using Medline (via Pubmed), Scopus, and Web of Science (until February 2022) databases to aggregate studies using m3D culture in which human tissues were mimicked. The search generated 3784 records, of which 25 met the inclusion criteria. The usability of these m3D systems for the development of homotypic or heterotypic spheroids with or without scaffolds was explored in these studies. We also explore methodological differences specifically related to the magnetic method. Generally, the development of m3D cultures has been increasing, with bioprinting and levitation systems being the most used to generate homotypic or heterotypic cultures, mainly to mimic the physiology of human tissues, but also to perform therapeutic screening. This systematic review showed that there are areas of research where the application of this method remains barely explored, such as cancer research.
Breast cancer (BC) is a malignant neoplasia with the highest incidence and mortality rates in women worldwide. Currently, therapies include surgery, radiotherapy, and chemotherapy, including targeted ...therapies in some cases. However, treatments are often associated with serious adverse effects. Looking for new options in BC treatment, we evaluated the therapeutic potential of cold atmospheric plasma (CAP) in two cell lines (MCF7 and HCC1806) with distinct histological features. Apoptosis seemed to be the most prevalent type of death, as corroborated by several biochemical features, including phosphatidylserine exposure, the disruption of mitochondrial membrane potential, an increase in BAX/BCL2 ratio and procaspase 3 loss. Moreover, the accumulation of cells in the G2/M phase of the cell cycle points to the loss of replication ability and decreased survival. Despite reported toxic concentrations of peroxides in culture media exposed to plasma, intracellular peroxide concentration was overall decreased accompanying a reduction in GSH levels shortly after plasma exposure in both cell lines. In HCC1806, elevated nitric oxide (NO) concentration accompanied by reduced superoxide levels suggests that these cells are capable of converting plasma-derived nitrites into NO that competes with superoxide dismutase (SOD) for superoxide to form peroxinitrite. The concomitant inhibition of the antioxidative activity of cells during CAP treatment, particularly the inhibition of cytochrome c oxidase with sodium azide, synergistically increased plasma toxicity. Thus, this in vitro research enlightens the therapeutic potential of CAP in the treatment of breast cancer, elucidating its possible mechanisms of action.
Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. ...Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.
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