Cyclic compressive loading induces a mature meniscal cell phenotype in mesenchymal stem cells with an atelocollagen-based scaffold.

Introduction: Biomechanical stimulation is reportedly pivotal in meniscal regeneration, although its effect on mesenchymal stem cell (MSC) meniscal differentiation remains elusive. In this study, we investigated how cyclic compressive loading (CCL) could impact MSCs using three-dimensional cultures in atelocollagen-based meniscal substitute (ACMS). Methods: We extracted MSCs from the meniscus, synovium, and articular cartilage, cultured them in three-dimensional cultures, and exposed them to CCL for 7 days. We then compared the transcriptomes of MSCs treated with and without CCL. Results: Our RNA-seq analysis revealed that CCL induced significant transcriptome changes, significantly affecting chondrocyte-related genes, including SOX9, TGFB1, and PRG4 upregulation. CCL induced transcriptional differentiation of meniscus progenitors toward mature meniscal cells. Conclusion: This study unveils the potential of mechanical stress in promoting MSC meniscal differentiation within ACMS. Our investigations provide new insights for mechanisms underlying meniscal regeneration with ACMS.

Mechanical Thrombectomy for Basilar Artery Occlusion with a Type 1 Persistent Proatlantal Artery: A Case Report and Literature Review.

Objective: Persistent proatlantal artery (PPA) is a primitive carotid-vertebrobasilar anastomosis (CVA); acute ischemic stroke due to basilar artery (BA) occlusion via a PPA is extremely rare. Case Presentation: An 84-year-old female developed disturbance of consciousness (Glasgow Coma Scale E2V1M5) and quadriparesis with a National Institutes of Health Stroke Scale score of 35. Head CT revealed early ischemic changes in the right temporal lobe, and a hyperdense vessel sign in the BA. Cerebral angiography showed that the left vertebral artery (VA) did not originate from the left subclavian artery or aortic arch. A left common carotid artery angiogram showed the presence of the left PPA originating from the left external carotid artery. Mechanical thrombectomy (MT) with contact aspiration using a Penumbra 5MAX ACE 60 aspiration catheter was performed, and successful recanalization was achieved after clot retrieval in the first attempt (thrombolysis in cerebral infarction scale 2b). MRI performed the following day, however, revealed a newly developed large hemorrhagic infarction in the pons, with no improvement in her symptoms (modified Rankin Scale score of 5 at 90 days). Conclusion: Although MT achieved successful recanalization of the BA via the PPA, her clinical symptoms did not improve, probably because of poor collateral circulation or the long length of the occlusion. In patients with acute vertebro-BA occlusion, if the VA does not originate from the subclavian artery or aortic arch, the presence of a primitive CVA should be considered.

Pilocytic astrocytoma of the optic nerve with intracystic hemorrhage in an adult: illustrative case.

BACKGROUND: Optic pathway gliomas are uncommon, accounting for 3-5% of childhood brain tumors, and are mostly classified as pilocytic astrocytomas (PAs). PAs of the optic nerve are particularly rare in adults. OBSERVATIONS: The authors presented the case of PA of the left optic nerve in a 49-year-old woman along with detailed pathological and molecular analyses and sequential magnetic resonance imaging. The tumor had progressed during 5 years of follow-up along with cyst formation and intracystic hemorrhage; it had a thick capsule and contained xanthochromic fluid. The boundary between tumor and optic nerve was unclear. B-type Raf kinase (BRAF) V600E point mutations or translocations, IDH1-R132H mutations, loss of alpha-thalassemia/mental retardation X-linked, and 1p/19q codeletion were negative. LESSONS: BRAF alterations in pediatric PAs of the optic nerve are less frequent than those observed in PAs in other lesions; the same molecular pattern was observed in the adult case, without changes in BRAF. Surgical management should be indicated only in cases with severely impaired vision or disfigurement because there is no clear border between the tumor and optic nerve. Further discussion is needed to optimize the treatment for adult optic pathway gliomas, including radiotherapy, chemotherapy, and molecular-targeted therapies, in addition to surgical intervention.

Effects of tris(2-chloroethyl) phosphate exposure on chicken embryos in a shell-less incubation system.

Tris(2-chloroethyl) phosphate (TCEP) is an organophosphate flame retardant that used in textiles, industrial materials, and furniture to delay the spread of fire after ignition. TCEP has been detected in the tissues and eggs of fish and birds. However, there are no studies regarding the effects of TCEP on avian embryos. In the present study, we investigated the developmental toxicity of TCEP exposure on chicken embryos in a shell-less incubation system, which enables in situ observation. Chicken embryos were treated with graded doses of TCEP (50, 250, and 500 nmol/g egg) on incubation day 0. The survival rate, morphological biometrics, heart rate, and length and branch number of extraembryonic blood vessels were measured on incubation days 3-9. Survival rates were reduced from incubation day 3 and were significantly decreased until day 9. Body length, head + bill length and eye diameter were significantly reduced by TCEP exposure. Regarding skeletal effects, spine length was decreased in a dose-dependent manner on day 9. Body weight on day 9 significantly reduced in all TCEP treatment groups. These results suggest that TCEP exposure to >50 nmol/g egg retards development in chicken embryos. TCEP exposure to 500 nmol/g egg significantly increased heart weight to body weight ratio in the embryos. More than 250 nmol/g egg of TCEP significantly reduced the heart rate of embryos in the early developmental stage. The formation of extraembryonic blood vessels and the number of erythrocytes were significantly reduced even with 50 nmol/g egg of TCEP. These findings suggest that TCEP exposure specifically affects the cardiovascular system in chicken embryos, which leads to developmental delay. The results of this study also demonstrate that the shell-less incubation system can be used to continuously monitor the effects of chemicals on developing avian embryos.

In ovo exposure to triclosan alters the hepatic proteome in chicken embryos.

The occurrence of triclosan (TCS) in the eggs of wild avian species is an emerging concern. We previously evaluated the effects of in ovo exposure to TCS on the liver transcriptome of chicken embryos and proposed adverse outcome pathways (AOPs). However, the key molecular events identified to be affected need to be verified at the protein level. Herein, we investigated the changes in the spectrum of hepatic proteins in TCS-treated chicken embryos by proteomic analysis to validate the key signaling pathways involved in the AOPs. We identified and quantified 894 unique proteins using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry. In the 0.1 (low dose), 1 (median dose), and 10 µg triclosan/g egg (high dose) groups, TCS caused significant changes in the levels of 195, 233, and 233 proteins in males and 237, 188, and 156 proteins in females, respectively (fold changes > 1.3 or < 0.7). TCS exposure modulated the expression of proteins, predominantly involved in signaling pathways of lipid and energy metabolism in both genders. Among the proteins associated with TCS metabolism in the liver, phase I (e.g., CYP2C23a) and phase II (e.g., UGT1A1) enzymes mediated by chicken xenobiotic receptor, were only induced in males. In consonance with the malondialdehyde levels, which were increased upon TCS exposure in females in a dose-dependent manner, a battery of antioxidant enzymes, notably SOD2, GST, GSTz1, and PRDX1, was decreased and SOD1 and GSTK1 were increased in the embryos. Taken together, this proteome analysis complements the transcriptome profiling reported in our previous study and authenticates the AOPs proposed for chicken embryos in ovo exposed to TCS.

Effects on the hepatic transcriptome of chicken embryos in ovo exposed to phenobarbital.

This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 µg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders. In the PB treatment group, a 7% attenuation in tarsus length was found in females. While no adverse phenotypic effect on the liver somatic index (LSI) was observed, PB caused significant changes in the expressions of 52 genes in males and 516 genes in females (False Discovery Rate < 0.2, p value < 0.05, and absolute fold change > 2). PB exposure modulated the genes primarily enriched in the biological pathways of the cancer, cardiac development, immune response, lipid metabolism, and skeletal development in both genders, and altered expressions of genes related to the cellular process and neural development in females. However, mRNA expressions of chicken xenobiotic receptor (CXR)-mediated CYP genes were not induced in the PB treatment groups, regardless of males and females. On the contrary, PB exposure repressed the mRNA expressions of CYP2AC2 in males and CYP2R1, CYP3A37, and CYP8B1 in females. Although transcription factors (TFs) including SREBF1 and COUP-TFII were predicted to be commonly activated in both genders, some TFs were activated in a gender-dependent manner, such as PPARa in males and BRCA1 and IRF9 in females. Taken together, our results provided an insight into the mode of action of PB on the chicken embryos.

Effects of prenatal exposure to triclosan on the liver transcriptome in chicken embryos.

Triclosan (TCS), a commonly used antimicrobial compound, has recently been detected in the eggs of wild avian species. Exposure to TCS in rodents is known to interfere with thyroid hormone (TH), disrupt immune responses and cause liver disease. However, no attempt has been made to clarify the effects of TCS in avian species. The aim of this study is therefore to evaluate the toxic effects of in ovo exposure to TCS and explore the molecular mechanism by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were treated with graded concentration of TCS (0.1, 1 and 10 µg/g egg) at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At the administration of 10 µg TCS/g egg, embryo mortality increased from 20% in control to 37% accompanied with 8% attenuation in tarsus length. While liver somatic index (LSI) in TCS treatments was enhanced, statistical difference was only observed at the treatment of 0.1 µg TCS/g egg in females. The up-regulation of several crucial differentially expressed genes (DEGs) in transcriptome analysis suggested that TCS induced xenobiotic metabolism (e.g. CYP2C23a, CYP2C45 and CYP3A37 in males; CYP2C45 in females) and activated the thyroid hormone receptor (THR) - mediated downstream signaling (e.g. THRSPB and DIO2 in males; THRSPB in females). In females, TCS may further activate the lipogenesis signaling (e.g. ACSL5, ELOVL2) and repress the lipolysis signaling (e.g. ABHD5, ACAT2). A battery of enriched transcription factors in relation to these TCS-induced signaling and phenotypes were found, including activated SREBF1, PPARa, LXRa, and LXRb in males and activated GLI2 in females; COUP-TFII was predicted to be suppressed in both genders. Finally, we developed adverse outcome pathways (AOPs) that provide insights into the molecular mechanisms underlying the alteration of phenotypes.

Bis[1,2-bis-(eth-oxy-carbon-yl)ethene-1,2-dithiol-ato-κ(2) S,S']bis-(η(5)-penta-methyl-cyclo-penta-dien-yl)tetra-µ3-sulfido-diiron(IV)diiron(III)(3 Fe-Fe).

The title compound, [Fe4(C10H15)2(C8H10O4S2)2S4], contains a twisted Fe4S4 cubane-like core. A twofold rotation axis passes through the Fe4S4 core, completing the coordination of the four Fe atoms with two penta-methyl-cyclo-penta-dienyl ligands and two chelating dithiol-ate ligands. There are three short Fe-Fe and three long Fe⋯Fe contacts in the Fe4S4 core, suggesting bonding and non-bonding inter-actions, respectively. The Fe-S bonds in the Fe4S4 core range from 2.1523 (5) to 2.2667 (6) Šand are somewhat longer than the Fe-S bonds involving the dithiol-ate ligand.

Bis[1,2-bis-(meth-oxy-carbon-yl)ethene-1,2-dithiol-ato-κ(2) S,S']bis-(η(5)-penta-methyl-cyclo-penta-dien-yl)tetra-µ3-sulfido-tetra-iron(4 Fe-Fe) hexa-fluoridophosphate.

The asymmetric unit of the title compound, [Fe4(C6H6O4S2)2(C10H15)2S4]PF6, contains two different complex cations and two PF6 (-) anions. The two complex cations have similar conformations with the butterfly-like Fe4S4 core surrounded by two penta-methyl-cyclo-penta-dienyl ligands and the S atoms of two dithiol-ate ligands. In each Fe4S4 core, there are four short Fe-Fe and two long Fe⋯Fe contacts, suggesting bonding and non-bonding inter-actions, respectively. The Fe-S distances range from 2.1287 (13) to 2.2706 (16) Šfor one and from 2.1233 (13) to 2.2650 (16) Šfor the other Fe4S4 core. The Fe-S distances involving the dithiol-ate ligands are in a more narrow range [2.1764 (16)-2.1874 (13) Šfor one and 2.1743 (14)-2.1779 (16) Šfor the other cation]. There are no significant inter-actions between cations and anions.