Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal Stem Cells for Regenerative Medicine

In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.
The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models

Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in different lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that effectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment.
HIV status does not have an impact on positron emission tomography-computed tomography (PET-CT) findings or radiotherapy treatment recommendations in patients with locally advanced cervical cancer

Introduction Positron emission tomography-computed tomography (PET-CT) imaging is commonly used to identify nodal involvement in locally advanced cervical carcinoma, but its appropriateness for that purpose among HIV-positive patients has rarely been studied. We analyzed PET-CT findings and subsequent treatment prescribed in patients with locally advanced cervical carcinoma in Cape Town, South Africa. Methods We identified a cohort of consecutive cervical carcinoma patients International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB at our cancer center who underwent a planning 18-fluorodeoxyglucose (18FDG) PET-CT scan from January 2015 through December 2018. Demographics, PET-CT findings, and subsequent treatment prescribed were recorded. Patients were selected for PET-CT only if they had no signs of distant disease on staging chest X-ray or abdominal ultrasound; were deemed suitable for radical chemoradiation by the multi-disciplinary team; and had normal renal function. HIV-positive patients ideally had to have been established on continuous antiviral therapy for more than 3 months and to have a CD4 cell count above 150 cells/μL. Small cell and neuroendocrine carcinoma cases were excluded from the study. Differences in demographic and clinical measures between HIV-positive and HIV-negative patients were evaluated by means of t-tests for continuous variables and χ2 tests for categorical variables. Results Over a 4 year period, 278 patients—192 HIV-negative (69.1%) and 86 HIV-positive (30.9%)—met the inclusion criteria. HIV-positive patients had a median CD4 count of 475 cells/µL (IQR 307–612 cells/µL). More than 80% of patients had pelvic nodal involvement, and more than 40% had uptake in common iliac and/or para-aortic nodes. Nodal involvement was not associated with HIV status. Fifty-four patients (19.4%) had at least one site of distant metastatic disease. Overall, 235 patients (84.5%) were upstaged following PET-CT staging scan. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Ten patients who did not return for radiotherapy were excluded from the analysis. Following their PET-CT scan, treatment intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11). Conclusion We found no differences between HIV-positive or HIV-negative patients in nodal involvement or occult metastases, and PET-CT imaging did not lead to, or justify, treatment differences between the two groups. Future studies will evaluate survival and correlation of upstaging with outcome.
Speech Perception: Phonological Neighborhood Effects on Word Recognition Persist Despite Semantic Sentence Context

This study tested the hypothesis that two lexical properties, both phonological neighborhood density (ND) and neighborhood frequency (NF), influence the recognition of target words when preceded by either a semantically congruent or semantically neutral context. Our study is the first to test this hypothesis using a language other than English (i.e., Spanish). We used highly familiar bisyllabic nouns with medium-frequency occurrence as target words, and we expected recognition accuracy to increase as ND and NF decreased in both semanticallly congruent and semantically neutral sentences. We presented 48 undergraduate listeners with a set of 80 words, differing in ND and NF, within these two sentence contexts (i.e., 160 sentences). We then tested the relationships between ND, NF, and variations in semantic sentence context within a linear logistic model and found that words with a low frequency of neighbors were more likely to be correctly recognized in both sentence contexts. Thus, during word recognition, the influence of phonological competition outweighed semantic sentence context even when words were presented in Spanish.
Fine-Tuning of PGC1α Expression Regulates Cardiac Function and Longevity.

RATIONALE PGC1α represents an attractive target interfering bioenergetics and mitochondrial homeostasis, yet multiple attempts have failed to upregulate PGC1α expression as a therapy, for instance, causing cardiomyopathy. OBJECTIVE To determine whether a fine-tuning of PGC1α expression is essential for cardiac homeostasis in a context-dependent manner. METHODS AND RESULTS Moderate cardiac-specific PGC1α overexpression through a ROSA26 locus knock-in strategy was utilized in wild-type (WT) mice and in a third generation of telomerase-deficient (G3Terc-/-, hereafter as G3) mouse model, respectively. Ultrastructure, mitochondrial stress, echocardiographic, and a variety of biological approaches were applied to assess mitochondrial physiology and cardiac function. While WT mice showed a relatively consistent PGC1α expression from 3-month-old to 12-month-old, age-matched G3 mice exhibited declined PGC1α expression and compromised mitochondrial function. Cardiac-specific overexpression of PGC1α (PGC1αOE) promoted mitochondrial and cardiac function in 3-month old WT mice but accelerated cardiac aging and significantly shortened lifespan in 12-month old WT mice due to increased mitochondrial damage and ROS insult. In contrast, cardiac-specific PGC1α knock-in in G3 (G3 PGC1αOE) mice restored mitochondrial homeostasis and attenuated senescence-associated secretory phenotypes, thereby preserving cardiac performance with age and extending health span. Mechanistically, age-dependent defect in mitophagy is associated with accumulation of damaged mitochondria that leads to cardiac impairment and premature death in 12-month old WT PGC1αOE mice. Whereas in the context of telomere dysfunction, PGC1α induction replenished energy supply through restoring the compromised mitochondrial biogenesis and thus is beneficial to old G3 heart. CONCLUSIONS Fine-tuning the expression of PGC1α is crucial for the cardiac homeostasis, as the balance between mitochondrial biogenesis and clearance is vital for regulating mitochondrial function and homeostasis. These results reinforce the importance of carefully evaluating the PGC1α-boosting strategies in a context-dependent manner to facilitate clinical translation of novel cardioprotective therapies.
Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells.

The choroid plexus (CP), composed of capillaries surrounded by a barrier epithelium, is the main producer of cerebrospinal fluid (CSF). The CP epithelium regulates the transport of ions and water between the blood and the ventricles, contributing to CSF production and composition. Several studies suggest a connection between the cation channel Transient Receptor Potential Vanilloid-4 (TRPV4) and transepithelial ion movement. TRPV4 is a non-selective, calcium permeable cation channel present in CP epithelia reported to be activated by cytokines and inflammatory mediators. Utilizing the PCP-R (porcine choroid plexus- Riems) cell line, we investigated the effects of various cytokines and inflammatory mediators on TRPV4-mediated activity. Select pro-inflammatory cytokines (TNF-α, IL-1β, TGF-β1) had inhibitory effects on TRPV4-stimulated transepithelial ion flux and permeability changes whereas anti-inflammatory cytokines (IL-10, IL-4, IL-6) had none. Quantitative mRNA analysis showed that these cytokines had no effect on TRPV4 transcription levels. Inhibition of the transcription factor NF-κB, involved in the production and regulation of several inflammatory cytokines, inhibited TRPV4-mediated activity, suggesting a link between TRPV4 and cytokine production. Contrary to published studies, the pro-inflammatory mediator arachidonic acid (AA) had inhibitory rather than stimulatory effects on TRPV4-mediated responses. However, inhibition of AA metabolism also caused inhibitory effects on TRPV4, suggesting a complex interaction of AA and its metabolites in the regulation of TRPV4 activity. Together these data imply that TRPV4 activity is involved in the inflammatory response; it is negatively affected by pro-inflammatory mediators. Furthermore, arachidonic acid metabolites, but not arachidonic acid itself, are positive regulators of TRPV4.
Increased Expression of miR-494 in Serum of Patients with Prostate Cancer and its Potential Diagnostic Value.

BACKGROUND Prostate cancer is a common male cancer with poor prognosis, and to find molecular diagnostic markers for the early diagnosis of prostate cancer is urgently needed. The aim of this study is to investigate the diagnostic value of serum expression level of miR-494 for prostate cancer. METHODS Ninety patients with prostate cancer and 90 patients with benign prostatic hyperplasia were enrolled in this study, and 90 healthy volunteers served as the control group. The serum of the participants was collected, and the expression level of miR-494 was measured by RT-PCR. Then the relationship between the expression of miR-494 and the clinical characteristics of the patients was analyzed. Moreover, the correlation between the expression of miR-494 and the Gleason score as well as serum level of prostate specific antigen (PSA) were analyzed. Finally, the diagnostic value of miR-494 for the early diagnosis of prostate cancer was analyzed by ROC curve. RESULTS miR-494 was significantly increased in the prostatic hyperplasia group compared with the control group, and the level of miR-494 in the prostate cancer group was significantly higher than that in the prostatic hyperplasia group. The level of miR-494 in patients with prostate cancer was positively correlated with tumor size and tumor stage. Moreover, the level of miR-494 was positively correlated with the Gleason score (r = 0.3371, p = 0.0012) and serum level of PSA (r = 0.3485, p = 0.0008) in patients with prostate cancer. Finally, AUC of miR-494 was 0.8090 (95% confidence interval 0.7343 to 0.8837), suggesting that miR-494 is a sensitive biomarker for the diagnosis of prostate cancer. CONCLUSIONS miR-494 was upregulated in the serum of the patients with prostate cancer and circulating miR-494 can be used as a biomarker for the early diagnosis of prostate cancer.
Pulsed seaweed subsidies drive sequential shifts in the effects of lizard predators on island food webs.

Most prominent theories of food web dynamics imply the simultaneous action of bottom-up and top-down forces. However, transient bottom-up effects resulting from resource pulses can lead to sequential shifts in the strength of top-down predator effects. We used a large-scale field experiment (32 small islands sampled over 5 years) to probe how the frequency and magnitude of pulsed seaweed inputs drives temporal variation in the top-down effects of lizard predators. Short-term weakening of lizard effects on spiders and plants (the latter via a trophic cascade) were associated with lizard diet shifts, and were more pronounced with larger seaweed inputs. Long-term strengthening of lizard effects was associated with lizard numerical responses and plant fertilisation. Increased pulse frequency reinforced the strengthening of lizard effects on spiders and plants. These results underscore the temporally variable nature of top-down effects and highlight the role of resource pulses in driving this variation.
The pervasive effects of timing of parental mental health disorders on adolescent deliberate self-harm risk

Children whose parents have mental health disorders are at increased risk for deliberate self-harm (DSH). However, the effect of timing of parental mental health disorders on adolescent DSH risk remains under-researched. The aim of this study was to investigate how parental hospital admissions for mental health disorders and/or DSH in different developmental periods impact on the child’s DSH risk in adolescence. A nested case-control sample was compiled from a total population cohort sample drawn from administrative health records in Western Australia. The sample comprised 7,151 adolescents who had a DSH-related hospital admission (cases), and 143,020 matched controls who hadn’t had a DSH-related hospital admission. The occurrence of parental hospital admissions related to mental health disorders and/or DSH behaviours was then analysed for the cases and controls. The timing of the parental hospital admissions was partitioned into four stages in the child’s life course: (1) pre-pregnancy, (2) pregnancy and infancy, (3) childhood, and (4) adolescence. We found that adolescents of a parent with mental health and/or DSH-related hospital admissions in all developmental periods except pregnancy and infancy were significantly more likely than controls to have a DSH-related hospital admission. Compared to parental hospital admissions that occurred during childhood and adolescence, those that occurred before pregnancy conferred a higher risk for adolescent DSH: adjusted odds ratio (aOR) = 1.25 for having only one parent hospitalised and 1.66 for having both parents hospitalised for mental health disorders; aOR = 1.97 for having any parent hospitalised for DSH, all being significant at the level of p < . 001. This study shows that timing is important for understanding intergenerational transmission of DSH risk. The pre-pregnancy period is as critical as period after childbirth for effective intervention targeting adult mental health disorders and DSH, highlighting the important role of adult mental health services in preventing DSH risk in future generations.
Myometrial Cells Stimulate Self‐Renewal of Endometrial Mesenchymal Stem‐Like Cells Through WNT5A/β‐Catenin Signaling

Human endometrium undergoes cycles of proliferation and differentiation throughout the reproductive years of women. The endometrial stem/progenitor cells contribute to this regenerative process. They lie in the basalis layer of the endometrium next to the myometrium. We hypothesized that human myometrial cells provide niche signals regulating the activities of endometrial mesenchymal stem‐like cells (eMSCs). In vitro coculture of myometrial cells enhanced the colony‐forming and self‐renewal ability of eMSCs. The cocultured eMSCs retained their multipotent characteristic and exhibited a greater total cell output when compared with medium alone culture. The expression of active β‐catenin in eMSCs increased significantly after coculture with myometrial cells, suggesting activation of WNT/β‐catenin signaling. Secretory factors in spent medium from myometrial cell culture produced the same stimulatory effects on eMSCs. The involvement of WNT/β‐catenin signaling in self‐renewal of eMSCs was confirmed with the use of WNT activator (Wnt3A conditioned medium) and WNT inhibitors (XAV939 and inhibitor of Wnt Production‐2 [IWP‐2]). The myometrial cells expressed more WNT5A than other WNT ligands. Recombinant WNT5A stimulated whereas anti‐WNT5A antibody suppressed the colony formation, self‐renewal, and T‐cell factor/lymphoid enhancer‐binding factor (TCF/LEF) transcriptional activities of eMSCs. Moreover, eMSCs expressed FZD4 and LRP5. WNT5A is known to activate the canonical WNT signaling in the presence of these receptor components. WNT antagonist, DKK1, binds to LRP5/6. Consistently, DKK1 treatment nullified the stimulatory effect of myometrial cell coculture. In conclusion, our findings show that the myometrial cells are niche components of eMSCs, modulating the self‐renewal activity of eMSCs by WNT5A‐dependent activation of WNT/β‐catenin signaling. Stem Cells 2019;37:1455–1466
Bioluminescent flashes drive nighttime schooling behavior and synchronized swimming dynamics in flashlight fish

Schooling fishes, like flocking birds and swarming insects, display remarkable behavioral coordination. While over 25% of fish species exhibit schooling behavior, nighttime schooling has rarely been observed or reported. This is due to vision being the primary modality for schooling, which is corroborated by the fact that most fish schools disperse at critically low light levels. Here we report on a large aggregation of the bioluminescent flashlight fish Anomalops katoptron that exhibited nighttime schooling behavior during multiple moon phases, including the new moon. Data were recorded with a suite of low-light imaging devices, including a high-speed, high-resolution scientific complementary metal-oxide-semiconductor (sCMOS) camera. Image analysis revealed nighttime schooling using synchronized bioluminescent flashing displays, and demonstrated that school motion synchrony exhibits correlation with relative swim speed. A computer model of flashlight fish schooling behavior shows that only a small percentage of individuals need to exhibit bioluminescence in order for school cohesion to be maintained. Flashlight fish schooling is unique among fishes, in that bioluminescence enables schooling in conditions of no ambient light. In addition, some members can still partake in the school while not actively exhibiting their bioluminescence. Image analysis of our field data and model demonstrate that if a small percentage of fish become motivated to change direction, the rest of the school follows. The use of bioluminescence by flashlight fish to enable schooling in shallow water adds an additional ecological application to bioluminescence and suggests that schooling behavior in mesopelagic bioluminescent fishes may be also mediated by luminescent displays.
Fetal bovine serum impacts the observed N‐glycosylation defects in TMEM165 KO HEK cells

TMEM165 is involved in a rare genetic human disease named TMEM165‐CDG (congenital disorders of glycosylation). It is Golgi localized, highly conserved through evolution and belongs to the uncharacterized protein family 0016 (UPF0016). The use of isogenic TMEM165 KO HEK cells was crucial in deciphering the function of TMEM165 in Golgi manganese homeostasis. Manganese is a major cofactor of many glycosylation enzymes. Severe Golgi glycosylation defects are observed in TMEM165 Knock Out Human Embryonic Kidney (KO HEK) cells and are rescued by exogenous manganese supplementation. Intriguingly, we demonstrate in this study that the observed Golgi glycosylation defect mainly depends on fetal bovine serum, particularly its manganese level. Our results also demonstrate that iron and/or galactose can modulate the observed glycosylation defects in TMEM165 KO HEK cells. While isogenic cultured cells are widely used to study the impact of gene defects on proteins' glycosylation patterns, these results emphasize the importance of the use of validated fetal bovine serum in glycomics studies.
Use of injectable platelet‐rich fibrin in the treatment of plasma cell mucositis of the oral cavity refractory to corticosteroid therapy: A case report

Plasma cell mucositis (PCM) is a rare benign disease affecting adults characterized by an erythematous mucosa, an epithelial hyperplasia, and a dense submucosal infiltration of mainly mature plasma cells. PCM has been treated with topical, intralesional, and systemic corticosteroids, antibiotics, and topical cyclosporin with unreliable results and questionable benefits. Here, we present a case of PCM, refractory to previous treatments, treated with i‐PRF (injectable platelet‐rich fibrin) injections. The infiltrations were performed once a week for 2 months. There were no adverse reactions to the treatment. The pain gradually reduced until the score of zero at the fourth infiltration, and the patient remained free of pain during the whole study period. Clinically, we did not obtain a complete healing of the lesion, but a reduced perilesional inflammatory infiltrate was observed at a distance. Therefore, we can conclude that i‐PRF has been effective in the management of pain in PMC but does not result in complete healing of the disease.
Association between an indel polymorphism within the distal promoter of EGLN2 and cancer risk: An updated meta‐analysis

The association between a 4‐bp indel polymorphism (rs10680577) within the distal promoter of EGLN2 and cancer risk has been investigated by several case–control studies in recent years, but investigation results were inconsistent. Thus, a systematic assessment of the association was performed based on a literature review and pooled analysis.