Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway.

Due to the challenge of prostate cancer (PCa) management, there has been a surge in efforts to identify more safe and effective compounds that can modulate the epithelial-mesenchymal transition (EMT) for driving metastasis. Holothurin A (HA), a triterpenoid saponin isolated from Holothuria scabra, has now been characterized for its diverse biological activities. However, the mechanisms of HA in EMT-driven metastasis of human PCa cell lines has not yet been investigated. Moreover, runt-related transcription factor 1 (RUNX1) acts as an oncogene in prostate cancer, but little is known about its role in the EMT. Thus, the purpose of this study was to determine how RUNX1 influences EMT-mediated metastasis, as well as the potential effect of HA on EMT-mediated metastasis in endogenous and exogenous RUNX1 expressions of PCa cell lines. The results demonstrated that RUNX1 overexpression could promote the EMT phenotype with increased EMT markers, consequently driving metastatic migration and invasion in PC3 cell line through the activation of Akt/MAPK signaling pathways. Intriguingly, HA treatment could antagonize the EMT program in endogenous and exogenous RUNX1-expressing PCa cell lines. A decreasing metastasis of both HA-treated cell lines was evidenced through a downregulation of MMP2 and MMP9 via the Akt/P38/JNK-MAPK signaling pathway. Overall, our approach first demonstrated that RUNX1 enhanced EMT-driven prostate cancer metastasis and that HA was capable of inhibiting the EMT and metastatic processes and should probably be considered as a candidate for metastasis PCa treatment.

Anatomical Variants Identified on Computed Tomography of Oropharyngeal Carcinoma Patients.

Background and Objectives: Anatomical variations in the head, neck and chest are common, and are observed as occasional findings on computed tomography (CT). Although anatomical variations are mostly asymptomatic and do not cause any negative influence on the body function, they may jeopardize diagnosis and may be confused with pathological conditions. The presence of variations may also limit surgical access during tumor removal. The aim of this study was to investigate the prevalence of six anatomical variations-os acromiale, episternal ossicles, cervical rib, Stafne bone cavity, azygos lobe and tracheal bronchus-in an open-access computed tomography dataset obtained from oropharyngeal cancer patients. Materials and Methods: A total of 606 upper-chest and neck computed-tomography scans (79.4% male and 20.6% female) were retrospectively investigated. Sex difference was evaluated using the z-test for two proportions. Results: Os acromiale, episternal ossicles, cervical rib, Stafne bone cavity, azygos lobe, and tracheal bronchus were present in 3.1%, 2.2%, 0.2%, 0%, 0.3% and 0.5%, respectively, of all patients. Os acromiale was identified as meso-acromion in 86.6%, and as pre-acromion in 17.4%, of all acromia. Episternal ossicles were present unilaterally in 58.3%, and bilaterally in 41.7%, of all sterna. Only the cervical rib showed a sex difference in prevalence. Conclusions: awareness of these variations is important for radiologists interpreting head, neck and chest CTs; for example, those of oropharyngeal cancer patients. This study also illustrates the applicability of publicly available datasets in prevalence-based anatomical research. While most of the variations investigated in the present study are well-known, the episternal ossicles are not well explored, and need further investigation.

The prevalence of anconeus epitrochlearis muscle and Osborne's ligament in cubital tunnel syndrome patients and healthy individuals: An anatomical study with meta-analysis.

BACKGROUND: Anconeus epitrochlaeris muscle and Osborne's ligament are anatomical variants that are occasionally found at the cubital tunnel of the elbow. In certain individuals, these two structures may compress the ulnar nerve resulting in a cubital tunnel syndrome. Although these variants have been reported extensively, its prevalence is still unclear and its contribution to cubital tunnel syndrome is debatable. The aim of this study is to generate weighted frequency values of the anconeus epitrochlearis and Osborne's ligament, as well as to identify any association of these two structures with gender, side, ethnicity and the development of cubital tunnel syndrome. METHODS: An anatomical study and a meta-analysis were performed to more accurately study the prevalence of anconeus epitrochlearis and Osborne's ligament. A total of 40 original studies including the present study met the inclusion criteria for meta-analysis and 6 case reports for descriptive analysis. RESULTS: Crude pooled prevalence estimate of the anconeus epitrochlearis was significantly higher (p < 0.001) in healthy subjects (14.2%) than in subjects diagnosed with cubital tunnel syndrome (4.5%). No significant difference was found for gender, side or laterality. The anconeus epitrochlearis was significantly more common in Europeans populations (18.2%) when compared with North American (6.8%) (p = 0.012) and Asian populations (7.5%) (p < 0.001). Anconeus epitrochlearis had a tendency to be hypertrophied when associated with cubital tunnel syndrome. The definition of Osborne's ligament is unclear, resulting in inconsistent reported prevalence across studies. CONCLUSION: The present study provides a more accurate estimate of anconeus epitrochlearis across the populations. There was a negative correlation between the presence of anconeus epitrochlearis and the development cubital tunnel syndrome, supporting the idea that the muscle may be protective against cubital tunnel syndrome. Future studies are needed to give proper definition of Osborne's ligament and accurately study its prevalence across populations.

The prevalence of the azygos lobe: A meta-analysis of 1,033,083 subjects.

The azygos lobe (AL) is an accessory lobe of the right lung with prevalence between 0.4 and 1.2%. The aim of the present review is to provide a better estimate of the frequency of the AL and to examine its relationships with other variables such as population, diagnostic methods, and co-occurring illnesses. Studies published between 1899 and October 2020 were searched through three electronic databases; Google Scholar, PubMed, and JSTOR. Titles, abstracts, and full texts of the retrieved entries were screened to determine their appropriateness for inclusion. A total of 88 studies relating to 1,033,083 subjects met the inclusion criteria. A random-effects meta-analysis yielded an overall prevalence of 0.30% (95% CI: 0.0024-0.0035, I2  = 97.9%). Linear regression and subgroup analysis revealed a negative correlation (ρ = -0.540, p <0.001) between AL prevalence and sample size; studies with smaller sample sizes had higher prevalences. The AL prevalence in individuals with congenital pulmonary defects, 5.2% (95% CI: 0.0018-0.0086, I2  = 0%), was 17 times higher than the overall prevalence (z = 6.65, p <0.001), suggesting associations with other abnormalities and possibly a genetic predisposition. In addition to an evidence-based synthesis of AL prevalence, this study demonstrates publication bias and small-study effects in the anatomy literature. Awareness of the AL is crucial for radiologists when they interpret unusual radiological findings and for surgeons when they operate in the region.

Normative Reference Values of the Tibial Nerve in Healthy Individuals Using Ultrasonography: A Systematic Review and Meta-Analysis.

BACKGROUND: High-resolution ultrasound of the tibial nerve has been used for screening of several neurologic disorders, but normative reference values of tibial nerve cross-sectional areas (CSA) have not been well established. Thus, the present meta-analysis was performed to generate normative estimates of tibial nerve CSA at various sites of the lower limb based on ultrasonography. METHODS: Google Scholar, Scopus and PubMed were searched for potential studies. Studies were required to report tibial nerve CSA in healthy individuals to be included. A random-effect meta-analysis was performed to calculate tibial nerve CSA values. Subgroup and statistical analyses were performed to study covariates. RESULTS: Forty-eight eligible articles consisting of 2695 limbs were included. The average tibial nerve CSA was found to be 10.9 mm2 at the ankle (95% CI: 9.9-11.8) and should not exceed 11.8 mm2 in healthy adults. At the popliteal fossa, the overall CSA was 21.7 mm2 (95% CI: 17.5-25.8) in healthy adults. At both sites, the average tibial nerve CSA was significantly larger in adults than in children, and the differences by geographical region were not statistically significant. At the ankle, tibial nerve CSA increased with age and body mass index, while at the popliteal fossa it increased with age and weight. CONCLUSIONS: our findings indicate that the tibial nerve varied not only along its course but also among sub-variables. Establishing normal references values of tibial nerve CSA is helpful to differentiate healthy from diseased tibial nerves such as in diabetic peripheral neuropathy or tarsal tunnel syndrome.

In vitro and in silico studies of holothurin A on androgen receptor in prostate cancer.

The androgen receptor (AR) plays a crucial role in the growth of prostate cancer, and has long been considered the cancer's primary strategic therapeutic target. However, despite the early susceptibility, patients receiving hormonal therapy targeting AR are likely to develops resistance to the treatment and progresses to the castration-resistant stage as a consequence of the mutation at the ligand binding pocket of AR. Interestingly, the surface pocket of the AR called binding function 3 (BF3) has been reported as a great benefit for treating a recurrent tumor. Herein, we investigate the potential of using a marine triterpenoid saponin, holothurin A, on targeting AR expression of prostate cancer using in vitro and in silico studies. Holothurin A reduced the PSA expression, leading to the growth inhibition of androgen sensitive prostate cancer cell line through a downregulation of AR activity. The molecular docking study demonstrated that holothurin A could bind strongly in the BF3 pocket by energetically favorable hydrogen acceptor and hydrophobic with a calculated binding affinity of -13.90 kcal/mol. Molecular dynamics simulations provided the additional evidence that holothurin A can form a stable complex with the BF3 pocket through the hydrophobic interactions with VAL676, ILE680, and ALA721. As a consequence, holothurin A modulates the activation function-2 (AF2) site of the AR through repositioning of the residues in the AF2 pocket. Targeting alternatives sites on the surface of AR via holothurin A will provide a potential candidate for future prostate cancer treatment.Communicated by Ramaswamy H. Sarma.

The decreasing prevalence of the thyroid ima artery: A systematic review and machine learning assisted meta-analysis.

INTRODUCTION: Thyroid ima artery is a variant artery found on the anterior surface of the trachea. The aim of this meta-analysis was to obtain pooled prevalence data of the thyroid ima artery and discuss its clinical importance especially for tracheostomy. METHODS: A systematic literature search was performed through five electronic databases until May 2021. A set of inclusion and exclusion criteria based on AQUA guidelines were used to select relevant studies. Meta-analysis, subgroup analyses, meta-regression, and tests for publication bias were performed. Factors that influence the prevalence of the thyroid ima artery were detected using simple and interpretable machine learning (linear regression and K means). RESULTS: Thirty-six studies with a total of 4335 subjects met the inclusion criteria. The prevalence of the thyroid ima artery was 3.8% (95% CI: 0.027-0.049, I2=56.2%). Machine learning identified age, region and year of publication as potential covariates. Subgroup analysis showed that the prevalence of the thyroid ima artery was 4.5 times higher in fetuses (14.8%) than adults (3.3%) (z=-6.76, p<0.01). There was a significant negative correlation between the adult prevalence of the thyroid ima artery and the year of publication (Pearson's r=-0.354, p=0.040) thereby suggesting a decline in thyroid ima artery prevalence over time. This artery, if present, may originate from the brachiocephalic trunk (74%), right common carotid artery (9.6%), arch of aorta (7.7%), right internal thoracic artery (4.8%), left common carotid artery (1.9%) and left internal thoracic artery (1.9%). CONCLUSION: In addition to evidence-based synthesis of the thyroid ima artery, this study is the first ever study to report the decreasing prevalence over time of a human body structure in the postnatal life. Knowledge of the thyroid ima artery is of vital importance for surgeons to avoid accidental hemorrhage during tracheostomy.

Altered oligodendrocytes in spinal enlargements of streptozotocin diabetic rats / Oligodendrocitos alterados en la intumescencia espinal de ratas diabéticas con estreptozotocina

SUMMARY: Disturbances of sensory and motor nerve conduction velocity in the spinal cord as well as degenerated myelin sheaths are observed in diabetic patients and animal models. Indeed, oligodendrocytes (OLs), which are important neuroglial cells, generate myelin in the central nervous system. Spinal enlargement, including cervical and lumbar enlargements, innervates all limbs. Thus, the purposes of this study were to examine and compare the ultrastructural alterations of OLs in spinal enlargements of streptozotocin (STZ)- induced diabetic rats and controls. Thirteen male Sprague-Dawley rats were induced with STZ in citrate buffer and six control rats were injected with the same buffer solution. All rats were sacrificed after inductions at four (short-term DM) and twenty-four weeks (long-term DM). The selected spinal enlargements were processed for transmission electron microscopy. The OL alterations in both the cervical and lumbar enlargements were apparently the same. In short-term DM, the nuclei of OLs became swelled with chromatin clumping. Cytoplasmic organelles were moderately damaged. In long-term DM, OLs contained shrinkage nuclei with thick heterochromatin clumping. Severely degenerated mitochondria with disrupted cristae and broken membranes were observed. Moreover, distended and fragmented rough endoplasmic reticulum were observed, and large clear areas were present in the cytoplasm. Additionally, the loosening, splitting, and destruction of myelin lamellae were found. This study can provide important preliminary information about the alteration of OLs in the spinal cords of diabetic patients, which might be involve in the impairments of sensory and motor conduction velocities in these individuals.

RESUMEN: En pacientes diabéticos y modelos animales se observan alteraciones de la velocidad de conducción nerviosa sensorial y motora en la médula espinal, así como vainas de mielina degeneradas. De hecho, los oligodendrocitos (OL), que son importantes células neurogliales, generan mielina en el sistema nervioso central. La intumescencia espinal, a nivel cervical y lumbar, inerva los miembros. Por lo tanto, los propósitos de este estudio fueron examinar y comparar las alteraciones ultraestructurales de los OL en la intumescencia espinal de ratas diabéticas inducidas por estreptozotocina (STZ) y controles. Se indujeron trece ratas macho Sprague-Dawley con STZ en tampón citrato y se inyectaron seis ratas de control con la misma solución tampón. Todas las ratas se sacrificaron después de la inducción a las cuatro (DM a corto plazo) y a las veinticuatro semanas (DM a largo plazo). Las ampliaciones de la columna seleccionadas se procesaron para microscopía electrónica de transmisión. Las alteraciones de OL en las intumescencias cervical y lumbar eran aparentemente las mismas. En la DM a corto plazo, los núcleos de los OL se hincharon con la acumulación de cromatina. Los orgánulos citoplasmáticos sufrieron daños moderados. En la DM a largo plazo, los OL contenían núcleos de contracción con aglutinación de heterocromatina gruesa. Se observaron mitocondrias severamente degeneradas con crestas y membranas rotas. Además, se observó un retículo endoplásmico rugoso distendido y fragmentado, y estaban presentes grandes áreas claras en el citoplasma. Además, se encontraron el aflojamiento, la división y la destrucción de las laminillas de mielina. Este estudio puede proporcionar información preliminar importante sobre la alteración de los OL en la médula espinal de los pacientes diabéticos, que podría estar involucrada en las alteraciones de las velocidades de conducción sensorial y motora en estos individuos.