Miracle-dz/UniFAR-FTUs huggingface dataset:
New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors

Osteoarthritis (OA) is the most common degenerative joint disease characterized by articular cartilage degradation and joint degeneration. The articular cartilage is mainly formed by chondrocytes and a collagen-proteoglycan extracellular matrix that contains high levels of glycosylated proteins. It was reported that the shift from glycoproteins containing α-2,6-linked sialic acids to those that contain α-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of α-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the α-2,3-sialylated transmembrane mucin receptor, known as podoplanin (PDPN). Additionally, the Maackia amurensis seed lectin (MASL), that can be utilized to target PDPN, attenuates the inflammatory response mediated by NF-kB activation in primary chondrocytes and protects human cartilage breakdown ex vivo and in an animal model of arthritis. These findings reveal that specific lectins targeting α-2,3-sialylated receptors on chondrocytes might effectively inhibit cartilage breakdown. We also present a computational 3D molecular model for this interaction. These findings provide mechanistic information on how a specific lectin could be used as a novel therapy to treat degenerative joint diseases such as osteoarthritis.
Comparative Analyses of mTOR/Akt and Muscle Atrophy-Related Signaling in Aged Respiratory and Gastrocnemius Muscles

Sarcopenia is the degenerative loss of skeletal muscle mass and function associated with aging and occurs in the absence of any underlying disease or condition. A comparison of the age-related molecular signaling signatures of different muscles has not previously been reported. In this study, we compared the age-related molecular signaling signatures of the intercostal muscles, the diaphragm, and the gastrocnemii using 6-month and 20-month-old rats. The phosphorylation of Akt, ribosomal S6, and Forkhead box protein O1 (FoxO1) in diaphragms significantly increased with age, but remained unchanged in the intercostal and gastrocnemius muscles. In addition, ubiquitin-proteasome degradation, characterized by the levels of MuRF1 and Atrogin-1, did not change with age in all rat muscles. Interestingly, an increase in LC3BII and p62 levels marked substantial blockage of autophagy in aged gastrocnemii but not in aged respiratory muscles. These changes in LC3BII and p62 levels were also associated with a decrease in markers of mitochondrial quality control. Therefore, our results suggest that the age-related signaling events in respiratory muscles differ from those in the gastrocnemii, most likely to preserve the vital functions played by the respiratory muscles.
Quality Parameters and Consumer Acceptance of Jelly Candies Based on Pomegranate Juice “Mollar de Elche”

There is an upward trend towards reducing or suppressing additives in foods, as well as reducing the use of E-numbers in labels providing clean label foods. Therefore, the development of confectionary products based exclusively on natural ingredients with antioxidant properties may offer valuable solutions to the confectionery industry. Fruit juices and purées may provide functional and organoleptic properties in jelly candies in a natural way. The consumption of pomegranate fruit and derivative products has increased due to their association with health benefits. The aim of this study was to determine consumer insights about pomegranate-based jellies, cultivar “Mollar de Elche”, as affected by formulation (100% pomegranate juice or 50%–50% pomegranate juice–apple purée) and type of sweetener (sugar or honey), and to link affective and descriptive data from sensory studies. The most valued quality parameter of pomegranate products, red color (measured by the green–red coordinate, a*), was not negatively affected by jelly preparation. It was determined that the main liking drivers for pomegranate jellies were intense red color and high brightness. The results might be used by pomegranate processing companies to improve their manufacturing protocols and to develop successful products meeting consumer demands and needs. The formulation containing 20% gelatin, pure “Mollar de Elche” pomegranate juice, 1% citric acid, and sucrose as sweetener provided the best quality of jellies in terms of color, texture, antioxidant capacity, and sensory attributes.
Cystic Fibrosis, CFTR, and Colorectal Cancer

Cystic fibrosis (CF), caused by biallelic inactivating mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, has recently been categorized as a familial colorectal cancer (CRC) syndrome. CF patients are highly susceptible to early, aggressive colorectal tumor development. Endoscopic screening studies have revealed that by the age of forty 50% of CF patients will develop adenomas, with 25% developing aggressive advanced adenomas, some of which will have already advanced to adenocarcinomas. This enhanced risk has led to new CF colorectal cancer screening recommendations, lowering the initiation of endoscopic screening to age forty in CF patients, and to age thirty in organ transplant recipients. The enhanced risk for CRC also extends to the millions of people (more than 10 million in the US) who are heterozygous carriers of CFTR gene mutations. Further, lowered expression of CFTR is reported in sporadic CRC, where downregulation of CFTR is associated with poor survival. Mechanisms underlying the actions of CFTR as a tumor suppressor are not clearly understood. Dysregulation of Wnt/β-catenin signaling and disruption of intestinal stem cell homeostasis and intestinal barrier integrity, as well as intestinal dysbiosis, immune cell infiltration, stress responses, and intestinal inflammation have all been reported in human CF patients and in animal models. Notably, the development of new drug modalities to treat non-gastrointestinal pathologies in CF patients, especially pulmonary disease, offers hope that these drugs could be repurposed for gastrointestinal cancers.
Effect of Storytelling Technique on the Attitudes of Nursing Students Toward Death

This study was conducted to determine the effect of the storytelling technique on the attitudes of nursing students toward death as a mixed research design. The study sample consisted of 94 senior students attending the nursing department of a university in Turkey. Quantitative data were collected by using the introductory characteristics form and the Death Attitude Profile-Revised, while qualitative data were collected through focus group interviews with the semistructured interview form. The data were analyzed according to number, percentage, Wilcoxon test, paired samples ttest, and descriptive analysis method. The mean Death Attitude Profile-Revised Scale score of the students before receiving the relevant education was 4.17 ± 0.21. This score increased to 4.25 ± 0.24 after the students received the education and the difference was found to be statistically significant (p < .05). In the qualitative section of the study, the data obtained from the attitudes of the students toward death were coded, and four themes were determined. The qualitative data obtained from the focus group interviews with the participating students were presented under four themes: the contribution of the storytelling technique to learning, the effect of the storytelling technique on the attitude toward death, thoughts about the storytelling technique, and contribution of the course to knowledge, skills and attitude in giving care to the dying patient. As a result of the study, explaining the subject of death with the storytelling technique was determined to positively affect the attitudes of the students toward death.
Activation of the SOX‐5, SOX‐6, and SOX‐9 Trio of Transcription Factors Using a Gene‐Activated Scaffold Stimulates Mesenchymal Stromal Cell Chondrogenesis and Inhibits Endochondral Ossification

Current treatments for articular cartilage defects relieve symptoms but often only delay cartilage degeneration. Mesenchymal stem cells (MSCs) have shown chondrogenic potential but tend to undergo endochondral ossification when implanted in vivo. Harnessing factors governing joint development to functionalize biomaterial scaffolds, termed developmental engineering, might allow to prime host MSCs to regenerate mature articular cartilage in situ without requiring cell isolation or ex vivo expansion. Therefore, the aim of this study is to develop a gene‐activated scaffold capable of delivering developmental cues to host MSCs, thus priming MSCs for articular cartilage differentiation and inhibiting endochondral ossification. It is shown that delivery of the SOX‐Trio induced MSCs to over‐express COL2A1 and ACAN and deposit a sulfated and collagen type II rich extracellular matrix while hypertrophic gene expression and collagen type X deposition is inhibited. When cell‐free SOX‐Trio‐activated scaffolds are implanted ectopically in vivo, they induced spontaneous chondrogenesis without evidence of hypertrophy. MSCs pre‐cultured on SOX‐Trio‐activated scaffolds prior to implantation differentiate into phenotypically stable chondrocytes as evidenced by a lack of collagen X expression or vascular invasion. This SOX‐trio‐activated scaffold represents a potent, single treatment, developmentally inspired strategy to prime MSCs in situ for articular cartilage defect repair.
The engaging nature of interactive gestures

The social interactions that we experience from early infancy often involve actions that are not strictly instrumental but engage the recipient by eliciting a (complementary) response. Interactive gestures may have privileged access to our perceptual and motor systems either because of their intrinsically engaging nature or as a result of extensive social learning. We compared these two hypotheses in a series of behavioral experiments by presenting individuals with interactive gestures that call for motor responses to complement the interaction (‘hand shaking’, ‘requesting’, ‘high-five’) and with communicative gestures that are equally socially relevant and salient, but do not strictly require a response from the recipient (‘Ok’, ‘Thumbs up’, ‘Peace’). By means of a spatial compatibility task, we measured the interfering power of these task-irrelevant stimuli on the behavioral responses of individuals asked to respond to a target. Across three experiments, our results showed that the interactive gestures impact on response selection and reduce spatial compatibility effects as compared to the communicative (non-interactive) gestures. Importantly, this effect was independent of the activation of specific social scripts that may interfere with response selection. Overall, our results show that interactive gestures have privileged access to our perceptual and motor systems, possibly because they entail an automatic preparation to respond that involuntary engages the motor system of the observers. We discuss the implications from a developmental and neurophysiological point of view.
Extreme Diversity of IgGs Against Histones, DNA, and Myelin Basic Protein in the Cerebrospinal Fluid and Blood of Patients with Multiple Sclerosis

It was recently shown that IgGs from sera of multiple sclerosis (MS) patients are active in the hydrolysis of DNA and myelin basic protein (MBP). We first analyzed the relative concentration of antibodies against five histones (H1, H2a, H2b, H3, and H4) in the cerebrospinal fluid (CSF) and serum of patients with MS. The relative concentrations of blood and CSF IgGs against histones and their activity in the hydrolysis of five histones varied greatly from patient to patient. However, all 28 IgG preparations were hydrolyzed from one to five histones. Relative activities and correlation coefficients among the activities of IgGs from serum and CSF in the hydrolysis of five histones (H1, H2a, H2b, H3, and H4), DNA, and MBP were calculated. It was shown that auto-IgGs from CSF and sera of MS patients are extremely heterogeneous in their affinity to histones, MBP, and DNA. The heterogeneity of IgG-abzymes hydrolyzing DNA, MBP, and histones from CSF and sera was also demonstrated using their isoelectrofocusing. The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10.
Therapeutic Potential of Dental Pulp Stem Cells and Leukocyte- and Platelet-Rich Fibrin for Osteoarthritis

Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte- and platelet-rich fibrin (L-PRF) emerges in regenerative medicine because of its growth factor content and fibrin matrix. This study evaluates the therapeutic application of DPSCs and L-PRF in OA via immunomodulation and cartilage regeneration. Chondrogenic differentiation of DPSCs, with or without L-PRF exudate (ex) and conditioned medium (CM), and of bone marrow-mesenchymal stem cells was compared. These cells showed differential chondrogenesis. L-PRF was unable to increase cartilage-associated components. Immature murine articular chondrocytes (iMACs) were cultured with L-PRF ex, L-PRF CM, or DPSC CM. L-PRF CM had pro-survival and proliferative effects on unstimulated and cytokine-stimulated iMACs. L-PRF CM stimulated the release of IL-6 and PGE2, and increased MMP-13, TIMP-1 and IL-6 mRNA levels in cytokine-stimulated iMACs. DPSC CM increased the survival and proliferation of unstimulated iMACs. In cytokine-stimulated iMACs, DPSC CM increased TIMP-1 gene expression, whereas it inhibited nitrite release in 3D culture. We showed promising effects of DPSCs in an in vitro OA model, as they undergo chondrogenesis in vitro, stimulate the survival of chondrocytes and have immunomodulatory effects.
Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.
Expression of the Novel Cardiac Biomarkers sST2, GDF-15, suPAR, and H-FABP in HFpEF Patients Compared to ICM, DCM, and Controls

Background: Heart failure with preserved ejection fraction (HFpEF) remains an ongoing therapeutic and diagnostic challenge to date. In this study we aimed for an analysis of the diagnostic potential of four novel cardiovascular biomarkers, GDF-15, H-FABP, sST2, and suPAR in HFpEF patients compared to controls as well as ICM, and DCM. Methods: In total, we included 252 stable outpatients and controls (77 DCM, 62 ICM, 18 HFpEF, and 95 controls) in the present study. All patients were in a non-decompensated state and on a stable treatment regimen. Serum samples were obtained and analyzed for GDF-15 (inflammation, remodeling), H-FABP (ischemia and subclinical ischemia), sST2 (inflammation, remodeling) and suPAR (inflammation, remodeling) by means of ELISA. Results: A significant elevation of GDF-15 was found for all heart failure entities compared to controls (p < 0.005). Similarly, H-FABP evidenced a significant elevation in all heart failure entities compared to the control group (p < 0.0001). Levels of sST2 were significantly elevated in ICM and DCM patients compared to the control group and HFpEF patients (p < 0.0001). Regarding suPAR, a significant elevation in ICM and DCM patients compared to the control group (p < 0.0001) and HFpEF patients (p < 0.01) was observed. An AUC analysis identified H-FABP (0.792, 95% CI 0.713–0.870) and GDF-15 (0.787, 95% CI 0.696–0.878) as paramount diagnostic biomarkers for HFpEF patients. Conclusion: Based on their differences in secretion patterns, novel cardiovascular biomarkers might represent a promising diagnostic tool for HFpEF in the future.
Effect of bariatric surgery on circulating FGF‐19: A systematic review and meta‐analysis

Fibroblast growth factor‐19 (FGF‐19) is a gut hormone which interacts with metabolism and is depleted in obesity. There is some indication that the hormone undergoes a resurgence following bariatric surgery (BS), an effect which may contribute to the beneficial outcomes of such procedures. This systematic review and meta‐analysis aims to synthesize the available literature on FGF‐19 levels before and after BS. MEDLINE, Scopus and Web of Science databases were searched, and the effect of different surgical procedures and degrees of body mass index (BMI) reduction on FGF‐19 levels was assessed by DerSimonian and Laird random‐effects model in meta‐analysis and dose–response analyses. This meta‐analysis, which included 474 patients from 25 arms undergoing one of five BS procedures, revealed a significant increase in the levels of circulating FGF‐19 following all‐type BS. Vertical sleeve gastrectomy, duodenal‐jejunal bypass liner and Roux‐en‐Y gastric bypass all significantly increased circulating FGF‐19 levels from baseline. However, gastric banding failed to achieve the same, and in fact, biliopancreatic diversion was associated with decreased circulating FGF‐19. Finally, an inverse association between FGF‐19 and the degree of BMI‐reduction post‐operatively was noted. FGF‐19 is increased by BS and may represent a pharmaceutical target in efforts to reproduce the beneficial effects of BS in a medical setting.
Inhibition of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor by Chrysin in a Rat Model of Choroidal Neovascularization

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Vascular endothelial growth factor (VEGF) is essential for choroidal neovascularization (CNV) development in advanced, wet AMD. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with anti-inflammatory, anti-oxidative, and anti-angiogenic effects. We hypothesized that intravitreally injected chrysin may inhibit CNV due to its inhibitory effect on angiogenesis. To determine the effects of chrysin on an experimental CNV model, we induced CNV in Brown Norway rats with a diode laser. One week later, rats were injected intravitreally with chrysin in the right eye and vehicle in the left eye. The following week, we evaluated chrysin’s effects via the CNV grade assessed with fluorescein angiography and histologic analyses. Hypoxia-inducible factor-1 alpha (HIF-1α) and VEGF expression in the retina/choroid complex were also measured in both eyes. The mean CNV grade was significantly lower in chrysin-treated vs. control eyes (2.34 ± 1.14 vs. 2.97 ± 1.05, p < 0.001), as was the mean CNV thickness (33.90 ± 4.89 vs. 38.50 ± 5.43 μm, p < 0.001) and mean HIF-1α and VEGF levels (both p < 0.001). Compared to chrysin-treated eyes, the relative risk of control eyes developing high-leakage lesions was 2.03 (95% confidence interval: 1.46–2.83). Since chrysin inhibited laser-induced CNV and downregulated HIF-1α and VEGF expression, it is a candidate for treating wet AMD and other CNV-associated conditions.
Nipah Virus: Past Outbreaks and Future Containment

Viral outbreaks of varying frequencies and severities have caused panic and havoc across the globe throughout history. Influenza, small pox, measles, and yellow fever reverberated for centuries, causing huge burden for economies. The twenty-first century witnessed the most pathogenic and contagious virus outbreaks of zoonotic origin including severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV) and Nipah virus. Nipah is considered one of the world’s deadliest viruses with the heaviest mortality rates in some instances. It is known to cause encephalitis, with cases of acute respiratory distress turning fatal. Various factors contribute to the onset and spread of the virus. All through the infected zone, various strategies to tackle and enhance the surveillance and awareness with greater emphasis on personal hygiene has been formulated. This review discusses the recent outbreaks of Nipah virus in Malaysia, Bangladesh and India, the routes of transmission, prevention and control measures employed along with possible reasons behind the outbreaks, and the precautionary measures to be ensured by private–public undertakings to contain and ensure a lower incidence in the future.
Threat-related motivational disengagement: Integrating blunted cardiovascular reactivity to stress into the biopsychosocial model of challenge and threat

ABSTRACT Background: The biopsychosocial model of challenge and threat specifies a challenge-threat continuum where favorable demand-resource evaluations, efficient cardiovascular responses, and superior performance characterize challenge; and maladaptive outcomes like clinical depression characterize threat states. The model also specifies task engagement, operationalized as heart rate and ventricular contractility increases, as a prerequisite for challenge and threat states. The blunted cardiovascular reactivity to stress literature describes reductions of these increases and associates them with problems like clinical depression. Objectives: To determine whether blunted cardiovascular reactivity to stress has implications for challenge and threat theory. Methods: We review and synthesize the literatures on blunted cardiovascular reactivity to stress and the biopsychosocial model. Results: Blunted cardiovascular reactivity appears not to reflect a physiological inability to respond to stress. Rather, it reflects a contextually dependent motivational dysregulation and reduced reactivity to stress consistent with deficient task engagement in the biopsychosocial model. Conclusion: We argue that blunted cardiovascular reactivity represents deficient task engagement, and more generally, motivational disengagement due to threat states. Our biopsychosocial model-based approach conceptualizes this motivational disengagement as a tendency to avoid motivated performance situations. This tendency may represent a defense mechanism against subsequent threat and might explain associations with disorders like clinical depression.