Biomedicines最新文献

With the increasing burden of osteoarthritis worldwide, cost efficient and reliable models are needed to enable the development of innovative therapies or therapeutic interventions. Ex vivo models have been identified as valuable modalities in translational research, bridging the gap between in vitro and in vivo models. Osteocartilaginous explants from Osteoarthritis (OA) patients offer an exquisite opportunity for studying OA progression and testing novel therapies. We describe the protocol for establishing human osteocartilaginous explants with or without co-culture of homologous synovial tissue. Furthermore, a detailed protocol for the assessment of explanted tissue in terms of protein content using Western blot and immunohistochemistry is provided. Commentaries regarding the technique of choice, possible variations and expected results are inserted.

Background/objectives: Recent epidemiological studies have revealed an upward trend in young-onset colorectal cancer (YOCRC) overall, whereas specific data on young-onset colorectal neuroendocrine neoplasms (YONEN) remain limited. This study investigated the demographic characteristics and survival trends in YONEN and compared these with those of young-onset colorectal adenocarcinoma (YOADC), the most common histologic subtype of YOCRC.

Methods: A retrospective analysis was conducted from 2000 to 2019 using the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were assessed using univariate and multivariable Cox proportional models, with demographic differences evaluated via Wilcoxon rank sum and Chi-square tests.

Results: Out of 61,705 patients aged 20-49 with colorectal cancer, 8% had NEN, and 92% had adenocarcinoma. The YONEN cohort had a higher proportion of Black patients and a lower proportion of White patients than the YOADC cohort (21% vs. 13% and 44% vs. 57%, respectively). NEN was more commonly found in the rectum (79%), and adenocarcinoma was mostly colonic (57%) in origin. YONEN patients had better survival than YOADC patients. Multivariate analysis in YONEN patients revealed that Hispanic patients had better overall survival compared to White patients (HR 0.67, 95% CI 0.47-0.95, p = 0.024).

Conclusions: Racial disparities should be investigated further to aid in policymaking and targeted interventions.

Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to classic inflammation markers (C Reactive Protein [CRP] and procalcitonin [PCT]) in patients admitted for CAP and their relationship with ICU admission, CVE and mortality in the short and long term; Methods: Biomarkers were analysed in 515 patients with CAP at day 1, 285 at day 5 and 280 at day 30. Traditional inflammatory biomarkers and endothelial damage biomarkers were measured. ICU admission, CVE and mortality (in-hospital and 1-year follow-up) were assessed using receiver operating characteristic (ROC) curve analysis and univariate logistic regression. Results: A statistically significant association was observed between initial, raised CT-proET-1 and MR-proADM levels, the need for ICU admission and the development of in-hospital CVE or in-hospital mortality. Both endothelial markers maintained a strong association at day 30 with 1-year follow-up CVE. At day 1, CRP and PCT were only associated with ICU admission. On day 30, there was no association between inflammatory markers and long-term CVE or death. The odds ratio (OR) and area under the curve (AUC) of endothelial biomarkers were superior to those of classic biomarkers for all outcomes considered. Conclusions: Endothelial biomarkers are better indicators than classic ones in predicting worse outcomes in both the short and long term, especially CVE. MR-proADM is the best biomarker for predicting complications in CAP.

(1) Background: Small ubiquitin-like modifiers (SUMOs) are pivotal in post-translational modifications, influencing various cellular processes, such as protein localization, stability, and genome integrity. (2) Methods: This review explores the SUMO family, including its isoforms and catalytic cycle, highlighting their significance in regulating key biological functions in thyroid cancer. We discuss the multifaceted roles of SUMOylation in DNA repair mechanisms, protein stability, and the modulation of receptor activities, particularly in the context of thyroid cancer. (3) Results: The aberrant SUMOylation machinery contributes to tumorigenesis through altered gene expression and immune evasion mechanisms. Furthermore, we examine the therapeutic potential of targeting SUMOylation pathways in thyroid cancer treatment, emphasizing the need for further research to develop effective SUMOylation inhibitors. (4) Conclusions: By understanding the intricate roles of SUMOylation in cancer biology, we can pave the way for innovative therapeutic strategies to improve outcomes for patients with advanced tumors.

Background: MicroRNAs (miRNAs) are crucial regulators of gene expression, playing significant roles in various cellular processes, including cancer pathogenesis. Traditional cancer diagnostic methods, such as biopsies and histopathological analyses, while effective, are invasive, costly, and require specialized skills. With the rising global incidence of cancer, there is a pressing need for more accessible and less invasive diagnostic alternatives.

Objective: This research investigates the potential of machine-learning (ML) models based on miRNA attributes as non-invasive diagnostic tools for oral cancer. Methods and Tools: We utilized a comprehensive methodological framework involving the generation of miRNA attributes, including sequence characteristics, target gene associations, and cancer-specific signaling pathways.

Results: The miRNAs were classified using various ML algorithms, with the BayesNet classifier demonstrating superior performance, achieving an accuracy of 95% and an area under receiver operating characteristic curve (AUC) of 0.98 during cross-validation. The model's effectiveness was further validated using independent datasets, confirming its potential clinical utility.

Discussion: Our findings highlight the promise of miRNA-based ML models in enhancing early cancer detection, reducing healthcare burdens, and potentially saving lives.

Conclusions: This study paves the way for future research into miRNA biomarkers, offering a scalable and adaptable diagnostic approach for various cancers.

Background/Objectives: Bladder cancer is a very important issue in contemporary urology. The aim of this pilot study was to assess for the first time the clinical utility of semaphorin 3C (sema3C) and 4A (sema4A) in patients with non-muscle-invasive bladder cancer (NMIBC). Methods: The experiment involved 15 patients with NMIBC and 5 patients without malignancies as the control group. Plasma and urinary concentrations of sema3C and sema4A were assessed by using an enzyme-linked immunosorbent assay (ELISA). Urinary sema4A concentration was below the detection level. Results: There was no statistically significant difference between patients and controls in terms of plasma sema4A and sema3C or urinary sema3C concentrations (p > 0.05). There was a significantly higher sema3C plasma concentration in patients with low-grade tumors (p = 0.0132) and an upward trend in sema4A plasma concentration for the subjects with Ta-stage tumors. Urinary sema3C concentration positively correlated with tumor size (R = 0.57, p = 0.03). Plasma sema3C concentration correlated negatively with tumor grade (R = -0.62, p = 0.01). Conclusions: Urinary sema4A concentration, which is below the detection threshold, is unlikely to be useful as a marker of NMIBC. Plasma sema4A concentration and sema3C concentration in plasma and urine cannot be used as stand-alone markers of NMIBC at this point. The plasma concentration of sema3C can potentially be considered in the future as a marker for tumors of lower grades. Plasma sema4A concentration could potentially be considered in the future as a marker for tumors of earlier stages. All of these observations are preliminary, so they have to be assessed in larger cohorts to make reliable recommendations. Nevertheless, our study lays the groundwork for further research to develop potential tests that could be used in daily practice to monitor and predict the course of cancer.

Backgrounds: Our recent analysis of 1200+ existing missense ACE mutations revealed that 400+ mutations are damaging and led us to hypothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of late-onset Alzheimer's disease (AD).

Methods: Here, we quantified blood ACE levels in EDTA plasma from 41 subjects with 10 different heterozygous ACE mutations, as well as 33 controls, and estimated the effect of these mutations on ACE phenotype using a set of mAbs to ACE and two ACE substrates.

Results: We found that relatively frequent (~1%) AD-associated ACE mutations in the N domain of ACE, Y215C, and G325R are truly damaging and likely transport-deficient, with the ACE levels in plasma at only ~50% of controls. Another AD-associated ACE mutation, R1250Q, in the cytoplasmic tail, did not cause a decrease in ACE and likely did not affect surface ACE expression. We have also developed a method to identify patients with anti-catalytic mutations in the N domain. These mutations may result in reduced degradation of amyloid beta peptide Aβ42, an important component for amyloid deposition. Consequently, these could pose a risk factor for the development of AD.

Conclusions: Therefore, a systematic analysis of blood ACE levels in patients with all ACE mutations has the potential to identify individuals at an increased risk of late-onset AD. These individuals may benefit from future preventive or therapeutic interventions involving a combination of chemical and pharmacological chaperones, as well as proteasome inhibitors, aiming to enhance ACE protein traffic. This approach has been previously demonstrated in our cell model of the transport-deficient ACE mutation Q1069R.

Despite all the progress made by science in the prevention and treatment of cardiovascular diseases and cancers, these are still the main reasons for hospitalizations and death in the Western world. Among the possible causes of this situation, disorders related to hyperinsulinemia and insulin resistance (Hyperin/IR) are still little-known topics. An analysis of the literature shows that this condition is a multiple risk factor for type 2 diabetes, cardiovascular diseases, cellular senescence and cancer, and neurodegenerative diseases. Hyperin/IR is progressively increasing worldwide, and its prevalence has now exceeded 50% of the general population and in overweight children. Asymptomatic or poorly symptomatic, it can last for many years before manifesting itself as diabetes, cardiovascular disease, neoplasm, cognitive deficit, or dementia, therefore leading to enormous social and healthcare costs. For these reasons, a screening plan for this pathology should be implemented for the purpose of identifying people with Hyperin/IR and promptly starting them on preventive treatment.

Apigenin is an organic flavonoid abundant in some plants such as parsley, chamomile, or celery. Recently, it has been investigated for several of its pharmacological characteristics, such as its ability to act as an antioxidant, reduce inflammation, and inhibit the growth of cancer cells. The purpose of this review is to provide a summary of the existing knowledge regarding the effects of apigenin on female reproductive systems and its dysfunctions. Apigenin can influence reproductive processes by regulating multiple biological events, including oxidative processes, cell proliferation, apoptosis, cell renewal and viability, ovarian blood supply, and the release of reproductive hormones. It could stimulate ovarian folliculogenesis, as well as ovarian and embryonal cell proliferation and viability, which can lead to an increase in fertility and influence the release of reproductive hormones, which may exert its effects on female reproductive health. Furthermore, apigenin could inhibit the activities of ovarian cancer cells and alleviate the pathological changes in the female reproductive system caused by environmental pollutants, harmful medications, cancer, polycystic ovarian syndrome, ischemia, as well as endometriosis. Therefore, apigenin may have potential as a biostimulator for female reproductive processes and as a therapeutic agent for certain reproductive diseases.

Background: Physiotherapy plays a key role in managing fibromyalgia, a multifaceted disorder, through a combination of active and passive treatments. The purpose of this review is to compare the efficacy of "hands-off" treatments alone versus the combination of "hands-off" and "hands-on" therapies. Methods: MEDLINE (PubMed), CENTRAL, and Embase were searched. English-language randomized controlled trials involving adults with fibromyalgia were included. The included studies were divided into subgroups to reduce the possible heterogeneity. We calculated the standardized mean difference or mean difference with 95% confidence intervals for the continuous data according to the outcome measures. We used the risk ratio for dichotomous data of the drop-out rate of the studies. Results: We included and analyzed seven RCTs. The meta-analysis showed no significant results in the outcomes, pain, QoL, health status, and drop-out rate. We found significant results (p < 0.001) in favor of combining "hands-off" and "hands-on" treatments for the rest quality (SMD 0.72, 95% CI 0.35 to 1.09). Conclusions: This review increases the treatment options available for clinicians. Up to now, the main guidelines on managing fibromyalgia suggest only approaches based on "hands-off" treatments. These findings suggest that other approaches based on mixed interventions combining "hands-off" and "hands-on" treatments did not reduce the patient outcomes. Moreover, the mixed intervention led to better results for the patients' sleep quality than the "hands-off" treatments alone.