The objective of this systematic review was to provide a compilation of all the literature available on the association between single-nucleotide polymorphisms (SNPs) in the genes involved in the ...metabolic pathway of vitamin D and overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). This systematic review was conducted in accordance with the PRISMA guidelines. It included all the literature published up to 1 November 2022 and was carried out in four databases (Medline PubMed, Scopus, Web of Science, and Embase), using the PICO strategy, with relevant keywords related to the objective. The quality of the studies included was evaluated with an assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. Six studies were included in this systematic review. Our findings showed that the BsmI (rs1544410), Cdx-2 (rs11568820), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236), rs4646536, rs6068816, rs7041, and rs10741657 SNPs in the genes that play a part in vitamin D synthesis (
,
), transport (
), and metabolism (
), as well as in the vitamin D receptor (
), are associated with OS and/or PFS in patients with NSCLC. The SNPs in
have been the most extensively analyzed. This systematic review summed up the available evidence concerning the association between 13 SNPs in the main genes involved in the vitamin D metabolic pathway and prognosis in NSCLC. It revealed that SNPs in the
,
,
,
, and
genes could have an impact on survival in this disease. These findings suggest the identification of prognostic biomarkers in NSCLC patients. However, evidence remains sparse for each of the polymorphisms examined, so these findings should be treated with caution.
Mesenchymal stromal cells (MSCs) represent a promising tool for therapy in regenerative medicine, transplantation, and autoimmune disease due to their trophic and immunomodulatory activities. ...However, we are still far from understanding the mechanisms of action of MSCs in these processes. Transforming growth factor (TGF)‐β1 is a pleiotropic cytokine involved in MSC migration, differentiation, and immunomodulation. Recently, glycoprotein A repetitions predominant (GARP) was shown to bind latency‐associated peptide (LAP)/TGF‐β1 to the cell surface of activated Foxp3+ regulatory T cells (Tregs) and megakaryocytes/platelets. In this manuscript, we show that human and mouse MSCs express GARP which presents LAP/TGF‐β1 on their cell surface. Silencing GARP expression in MSCs increased their secretion and activation of TGF‐β1 and reduced their proliferative capacity in a TGF‐β1‐independent manner. Importantly, we showed that GARP expression on MSCs contributed to their ability to inhibit T‐cell responses in vitro. In summary, we have found that GARP is an essential molecule for MSC biology, regulating their immunomodulatory and proliferative activities. We envision GARP as a new target for improving the therapeutic efficacy of MSCs and also as a novel MSC marker. Stem Cells 2015;33:183–195
Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using ...serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis.
Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type MSAp, 20 with cerebellar type MSAc; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture.
There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-α2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1β, TNF-α) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1α showed a strong and significant positive correlation with UMSARS-2 scores.
Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1α deserve consideration as potential diagnostic or severity biomarkers of MSA.
•CSF levels of 12 cytokines were higher in MSA (n = 39) vs. PD + controls (n = 19 & 15).•Younger age and increasing CSF levels of MCP-3 and MDC were MSA predictors in adjusted models.•CSF levels of fractalkine and MIP-1α correlated with UMSARS-2 scores.•CSF levels of these cytokines might be diagnostic or severity MSA biomarkers.
Background
The integration of 3D printing technology in hospitals is evolving toward production models such as point-of-care manufacturing. This study aims to present the results of the integration ...of 3D printing technology in a manufacturing university hospital.
Methods
Observational, descriptive, retrospective, and monocentric study of 907 instances of 3D printing from November 2015 to March 2020. Variables such as product type, utility, time, or manufacturing materials were analyzed.
Results
Orthopedic Surgery and Traumatology, Oral and Maxillofacial Surgery, and Gynecology and Obstetrics are the medical specialties that have manufactured the largest number of processes. Working and printing time, as well as the amount of printing material, is different for different types of products and input data. The most common printing material was polylactic acid, although biocompatible resin was introduced to produce surgical guides. In addition, the hospital has worked on the co-design of custom-made implants with manufacturing companies and has also participated in tissue bio-printing projects.
Conclusions
The integration of 3D printing in a university hospital allows identifying the conceptual evolution to “point-of-care manufacturing.”
Ultraviolet (UV) radiation, especially types A (UVA) and B (UVB), is one of the main causes of skin disorders, including photoaging and skin cancer. Ultraviolent radiation causes oxidative stress, ...inflammation, p53 induction, DNA damage, mutagenesis, and oxidation of various molecules such as lipids and proteins. In recent decades, the use of polyphenols as molecules with an antioxidant and anti-inflammatory capacity has increased. However, some of these compounds are poorly soluble, and information regarding their absorption and bioavailability is scarce. The main objective of this study was to compare the intestinal absorption and biological activity of apigenin and its more soluble potassium salt (apigenin-K) in terms of antioxidant and photoprotective capacity. Photoprotective effects against UVA and UVB radiation were studied in human keratinocytes, and antioxidant capacity was determined by different methods, including trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Finally, the intestinal absorption of both apigenins was determined using an in vitro Caco-2 cell model. Apigenin showed a slightly higher antioxidant capacity in antioxidant activity assays when compared with apigenin-K. However, no significant differences were obtained for their photoprotective capacities against UVA or UVB. Results indicated that both apigenins protected cell viability in approximately 50% at 5 J/m
of UVA and 90% at 500 J/m
of UVB radiation. Regarding intestinal absorption, both apigenins showed similar apparent permeabilities (
), 1.81 × 10
cm/s and 1.78 × 10
cm/s, respectively. Taken together, these results suggest that both apigenins may be interesting candidates for the development of oral (nutraceutical) and topical photoprotective ingredients against UVA and UVB-induced skin damage, but the increased water solubility of apigenin-K makes it the best candidate for further development.
Abatacept (ABA) is used as a first-line treatment in patients diagnosed with moderate and severe rheumatoid arthritis (RA). The interindividual response to ABA therapy is very variable in these ...patients. The objective of our study was therefore to investigate the role of polymorphisms of the
,
and
genes, as well as that of clinical factors of the disease, in the response to ABA in patients with RA. A retrospective cohort study was carried out in 109 patients receiving treatment with ABA and diagnosed with RA. The genetic variables were analyzed using real-time PCR with TaqMan
probes. The patients were classified according to the European League Against Rheumatism (EULAR) criteria at 6 and 12 months from start of treatment. The independent variables associated with higher EULAR response were lower duration of previous biologic disease-modifying anti-rheumatic drugs and lower baseline values of the disease activity score 28 after 6 months of ABA treatment; and lower baseline patient's visual analogue scale (PVAS) after 12 months. In addition, a significant association was found between duration of ABA treatment, non-administration of concomitant glucocorticoids and lower baseline values of the number of inflamed joints and erythrocyte sedimentation rate clinical variables, with remission of the disease after 6 months' treatment with ABA. Finally, remission of the disease after 12 months' treatment with ABA was associated with earlier age at start of ABA therapy and lower number of previous biologic therapies (BTs). The
allele and the
allele were found to be associated with satisfactory EULAR response and low disease activity (LDA) after 12 months' treatment with ABA (
; OR = 5.88; CI
= 1.48-23.29 and OR = 4.75; CI
= 1.35-17.94, respectively, and
, OR = 3.48; CI
= 1.20-10.09 and OR = 4.68; CI
= 1.49-17.94, respectively). In conclusion, patients with RA treated with ABA showed better EULAR response and LDA rate when they had the
or
polymorphisms; furthermore, this remission rate increased in patients that began ABA treatment earlier, those with a lower number of previous BTs and those with a lower PVAS value.
Gynecological cancer accounts for an elevated incidence worldwide requiring responsiveness regarding its care. The comprehensive genomic approach agrees with the classification of certain tumor ...types. We evaluated 49 patients with gynecological tumors undergoing high-throughput sequencing to explore whether identifying alterations in cancer-associated genes could characterize concrete histological subtypes. We performed immune examination and analyzed subsequent clinical impact. We found 220 genomic aberrations mostly distributed as single nucleotide variants (SNV, 77%). Only 3% were classified as variants of strong clinical significance in BRCA1 and BRCA2 of ovarian high-grade serous (HGSC) and uterine endometrioid carcinoma. TP53 and BRCA1 occurred in 72% and 28% of HGSC. Cervical squamous cell carcinoma was entirely HPV-associated and mutations occurred in PIK3CA (60%), as well as in uterine serous carcinoma (80%). Alterations were seen in PTEN (71%) and PIK3CA (60%) of uterine endometrioid carcinoma. Elevated programmed death-ligand 1 (PD-L1) was associated with high TILs. Either PD-L1 augmented in deficient mis-matched repair (MMR) proteins or POLE mutated cases when compared to a proficient MMR state. An 18% received genotype-guided therapy and a 4% immunotherapy. The description of tumor subtypes is plausible through high-throughput sequencing by recognizing clinically relevant alterations. Additional concomitant assessment of immune biomarkers identifies candidates for immunotherapy.
The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to ...interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the
,
,
,
, and
genes, for treatment with natalizumab,
, for fingolimod and dimethyl fumarate,
, for cladribine, and
, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.
Colorectal cancer is the third most common diagnosed cancer globally. Although substantial advances have been obtained both in treatment and survival rates, there is still a need for new ...therapeutical approaches. Natural compounds are a realistic source of new bioactive compounds with anticancer activity. Among them, rosemary polyphenols have shown a vast antiproliferative capacity against colon cancer cells in vitro and in animal models. We have investigated the antitumor activity of a rosemary extract (RE) obtained by using supercritical fluid extraction through its capacity to inhibit various signatures of cancer progression and metastasis such as proliferation, migration, invasion and clonogenic survival. RE strongly inhibited proliferation, migration and colony formation of colon cancer cells regardless their phenotype. Treatment with RE led to a sharp increase of intracellular ROS that resulted in necrosis cell death. Nrf2 gene silencing increased RE cytotoxic effects, thus suggesting that this pathway was involved in cell survival. These in vitro results were in line with a reduction of tumor growth by oral administration of RE in a xenograft model of colon cancer cells using athymic nude mice. These findings indicate that targeting colon cancer cells by increasing intracellular ROS and decreasing cell survival mechanisms may suppose a therapeutic option in colon cancer through the combination of rosemary compounds and chemotherapeutic drugs.
Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in ...response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as being active or potentially active in cancer treatment in the past seventeen years (from January 2000 until April 2017) and describes their putative mechanisms of action. The structural diversity of MNPs is also highlighted and compared with the small-molecule anticancer drugs in clinical use. In addition, this review examines the use of virtual screening for MNP-based drug discovery and reveals that classical approaches for the selection of drug candidates based on ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering may miss potential anticancer lead compounds. Finally, we introduce a novel and publically accessible chemical library of MNPs for virtual screening purposes.
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