Particulate matter exposure induces adverse effects on endometrium and fertility via aberrant inflammatory and apoptotic pathways in vitro and in vivo.

This study aimed to evaluate the adverse effects of particulate matter (PM) exposure on endometrial cells and fertility and to identify possible underlying mechanisms. Thirteen women (aged 15-52 years) were included in this study. Enrolled patients underwent laparoscopic surgery at Gangnam Severance Hospital between 1 January and 31 December 2021. For in vivo experiments, 36 female and nine male C57BL/6 mice were randomly divided into control(vehicle), low-dose(10 mg/kg/d), and high-dose exposure groups(20 mg/kg/d). PM was inhaled nasally for four weeks and natural mating was performed. NIST® SRM® 1648a was used for PM exposure. qRT-PCR, western blotting and Masson's trichrome staining were performed. PM treatment in human endometrial stromal cells induced inflammation with significant upregulation of IL-1ß, p-NF-kB, and p-c-Jun compared to those of controls. Additionally, PM treatment significantly increased apoptosis in human endometrial stromal cells by downregulating p-AKT and upregulating p-p53/p53, Cas-3, BAX/Bcl-2, p-AMPK, and p-ERK. After PM treatment, the relative expression of IL-1ß, IL-6, TNF-α, p-NF-κB, p-c-Jun, and p-Nrf2/Nrf2 significantly increased in murine endometrium compared to those of the controls. Expression of apoptotic proteins p53, p27, and Cas-3, was also significantly elevated in murine endometrium of the PM exposure group compared to that of the controls. A significant increase in expression of procollagen Ⅰ, and Masson's trichrome staining scores in the murine endometrium was noted after PM treatment. PM treatment significantly decreased ERα expression. After natural mating, all 3 female mice in the control group gave birth to 25 offspring (mean 8.1), whereas in the low-dose PM treatment group, two of three female mice gave birth to nine offspring (mean 4.5). No pregnant mice or offspring was present in the high-dose PM treatment group. PM exposure induces adverse effects on the endometrium through aberrant activation of inflammatory and apoptotic pathways and is associated with detrimental effects on murine fertility.

Electronic Effect on Phenoxide Migration at a Nickel(II) Center Supported by a Tridentate Bis(phosphinophenyl)phosphido Ligand.

A phosphide nickel(II) phenoxide pincer complex (2) reacts with CO(g) to give a pseudo-tetrahedral nickel(0) monocarbonyl complex (3) possessing a phosphinite moiety. This metal-ligand cooperative (MLC) transformation occurs with a (PPP)Ni scaffold (PPP- = P[2-PiPr2-C6H4]2-), which can accommodate both square planar and tetrahedral geometries. The 2-electron reduction of a nickel(II) species induced by CO coordination involves group transfer to generate a P-O bond. For better mechanistic understanding, a series of nickel(II) phenolate complexes (2a-2e, XC6H4O- (X = OMe, Me, H, and CF3) and pentafluorophenolate) were prepared. Kinetic experimental data reveal that a phenolate species with an electron-withdrawing group reacts faster than those with electron-donating groups. The reaction kinetic experiments were conducted in pseudo-first order conditions at room temperature monitored by UV-vis spectroscopy. A pentafluorophenolate nickel(II) complex (2e) reveals instantaneous reactions even at -40 °C to give a nickel(0) monocarbonyl species (3e) and the reverse reaction is also possible. According to kinetic experiments, the rate determining step (RDS) would be the formation of a 5-coordinate intermediate 4 with a negative entropy value (ΔS‡ < 0), and a positive ρ value based on the Hammett plot indicates that the electron-deficient phenolate leads to a faster CO association. Furthermore, scramble experiments suggest that phenolate de-coordinates from the intermediate 4, which gives a (PPP)Ni-CO species 6. The cationic nickel monocarbonyl intermediate can possess a P--Ni(II), P•-Ni(I), or even a P+-Ni(0) character. Such an inner-sphere electron transfer is suggested when a π-acidic ligand such as CO coordinates to a metal ion. Another possible reaction is homolysis of a Ni-O bond to give P--Ni(I) or P•-Ni(0), when a phenoxyl radical is liberated. Considering the P-O bond formation, closed-shell nucleophilic and open-shell radical pathways are suggested. A phenolate pathway reveals a lower energy state for 2e relative to other complexes (2c and 2d), while its radical pathway undergoes via a higher energy state. Therefore, the formation of a P-O bond may occur with the binding of a closed-shell phenolate to the electron-deficient P center.

Ultrasonographic Carotid Artery Flow Measurements as Predictors of Spinal Anesthesia-Induced Hypotension in Elderly Patients: A Prospective Observational Study.

BACKGROUND In elderly patients, spinal anesthesia-induced hypotension (SAH) can be frequently caused by reduced preload and stiff ventricles. The primary purpose of this study was to investigate the ability of ultrasonographic carotid artery flow measurements during the passive leg raise (PLR) test to predict SAH in elderly patients. The correlation between preoperative transthoracic echocardiography (TTE) measurements and SAH was also investigated. MATERIAL AND METHODS The patients aged over 65 years scheduled for elective surgery under spinal anesthesia were recruited. Preoperative TTE was performed in all patients. Corrected carotid flow time and carotid blood flow were measured in the supine, semirecumbent, and PLR positions. Ultrasonographic carotid artery flow and preoperative TTE measurements were compared between patients who developed SAH and those who did not. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to test the association with SAH. RESULTS SAH occurred in 17 of 50 patients. Carotid blood flow in the semirecumbent position and preoperative mitral inflow E velocity could predict SAH, showing an area under the ROC curve of 0.754 (95% CI, 0.612-0.865) and 0.775 (95% CI, 0.634-0.881), respectively. However, according to the multivariate analysis, the independent risk factor for SAH was mitral inflow E velocity (OR 0.918, 95% CI 0.858-0.982, P=0.013). CONCLUSIONS In elderly patients, ultrasonographic carotid artery flow measurements failed to predict the occurrence of SAH. Only preoperative mitral inflow E velocity of TTE was selected as an independent risk factor for SAH.

CT arthrography visualizes tissue growth of osteochondral defects of the talus after microfracture.

PURPOSE: Little is known about the arthroscopic or radiographic outcomes after arthroscopic microfracture of osteochondral lesions of the talus (OLTs). The purpose of this study was to investigate tissue growth after arthroscopic microfracture of OLTs using computed tomography arthrography (CTA) and to identify the relationship between CTA findings and clinical outcomes. We hypothesized that the morphology of the repaired tissue would be similar to that of normal anatomy and correlate with the clinical outcomes. METHODS: Forty-two ankles treated using arthroscopic microfracture of OLTs between 2009 and 2014 were monitored. CTA was performed post-operatively at 6 months and at 1 and 2 years after surgery. The post-operative thickness of the repaired tissue associated with OLT (grade) and the volume of the subchondral cystic lesions were evaluated using CTA. Clinical outcomes, including the pain visual analog scale (VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) ankle functional scores, were evaluated and correlated with CTA. RESULTS: The proportion of fully grown tissue (grade 3) increased over time; specifically, the rates were 12/40 (33.3%) at 6 months, 11/18 (61.1%) at 1 year, and 8/10 (80%) at 2 years after surgery (p = 0.005). The VAS pain (p < 0.001) and AOFAS scores (p < 0.001) were also improved at the final follow-up; however, they were not associated with repaired tissue thickness as shown by CTA (n.s.). CONCLUSIONS: After microfracture of OLTs, tissue growth in the osteochondral defects was well visualized using CT arthrography and was observed in most cases. However, the CTA findings were not related to the clinical outcomes. LEVEL OF EVIDENCE: IV.

Magnetic Resonance Imaging and Stress Radiography in Chronic Lateral Ankle Instability.

BACKGROUND: Studies regarding magnetic resonance imaging (MRI) findings of the lateral ankle ligaments in chronic lateral ankle instability and their clinical relevance for surgery are lacking. This study classified the lateral ankle ligament MRI findings of the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) in chronic lateral ankle instability (CLAI) and correlated these findings with ankle stress radiographs. METHODS: We included 132 ankles with CLAI that underwent ligament reconstructions from 2006 to 2013. The distributions of the ATFL and CFL morphologies were evaluated using the following categories: (1) the amount of thickness: normal/thickened/attenuated/non-visualized, (2) the presence of discontinuity, (3) wavy or irregular contour, and (4) increased signal intensity on T2-weighted images. The relationships between the ligament morphologies and stress radiographs were analyzed. RESULTS: The ATFL was normal in 5 (4%) ankles, thickened in 35 (27%), attenuated in 76 (58%), and non-visualized in 16 (12%), while the CFL was normal in 39 (30%) ankles, thickened in 42 (32%), attenuated in 44 (33%), and non-visualized in 7 (5%). Discontinuity of the ATFL or CFL was observed in 46 (35%) ankles. Wavy or irregular contours were observed in 55 (42%) ATFLs and 37 (28%) CFLs, and signal intensity of both ligaments was increased in 19 (14%) ankles. ATFL ( P < .001) and CFL thickness ( P = .007) correlated with the talar tilt angle. CONCLUSIONS: The MRI findings of CLAI showed several morphologies and specific incidences for each morphology. Attenuated, wavy appearance was the most frequent MRI pattern. Thickness was related to the degree of instability. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Epithelioid Sarcoma in the Cervical Spine: A Case Report.

Epithelioid sarcoma is a rare and highly malignant soft tissue neoplasm that most commonly occurs in the long bones. This uncommon tumor has a poor clinical outcome, and the modality of its treatment has not yet been fully established. The authors report an extremely rare presentation of epithelioid sarcoma in the cervical spine, along with its clinical progression, imaging, and pathology. The patient underwent three surgical procedures and adjuvant radiochemical management. He survived for 25 months with a good general condition and adapted well to his social activity. Systemic metastasis was not found, but the patient died of respiratory failure due to direct tracheal invasion of the tumor.

Oral administration of Lactobacillus plantarum lysates attenuates the development of atopic dermatitis lesions in mouse models.

Lactobacillus plantarum is a well-documented probiotic that has been used in clinical trials for the regulation of the immune system and treatment of gastrointestinal diseases. In this study, we evaluated the effects of L. plantarum cell lysates on the immune regulation through the in vitro and in vivo studies. L. plantarum lysates were prepared by sonication method, and we observed that the repetition of disruption step increased indicator components within the bacterial lysates. Indicator components might affect TNF-α production. L. plantarum lysates did not induce TNF-α production, while LPS-induced TNF-α production was dramatically inhibited in a sonication-dependent manner in THP-1 cells. Oral administration of L. plantarum lysates effectively attenuated the horny layer formation and decreased epidermal thickening in NC/Nga mice skin. The damage to barrier function after the 8 weeks oral administration was reduced by L. plantarum lysates as compared to that in the atopic dermatitis (AD) mice. Further study revealed that L. plantarum lysates polarized Th1 response via induction of IL-12 and IFN-γ production and inhibition of IL-4 and IgE production in NC/Nga mice. Together, our results suggest that L. plantarum lysates are remarkable material for host homeostasis and it could be used for the treatment of inflammatory diseases.

Lipoteichoic acid isolated from Lactobacillus plantarum suppresses LPS-mediated atherosclerotic plaque inflammation.

Chronic inflammation plays an important role in atherogenesis. Experimental studies have demonstrated the accumulation of monocytes/macrophages in atherosclerotic plaques caused by inflammation. Here, we report the inhibitory effects of lipoteichoic acid (LTA) from Lactobacillus plantarum (pLTA) on atherosclerotic inflammation. pLTA inhibited the production of proinflammatory cytokines and nitric oxide in lipopolysaccharide (LPS)-stimulated cells and alleviated THP-1 cell adhesion to HUVEC by down-regulation of adhesion molecules such as intracellular adhesion molecule-1 (ICAM-I), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. The inhibitory effect of pLTA was mediated by inhibition of NF-κB and activation of MAP kinases. Inhibition of monocyte/macrophage infiltration to the arterial lumen was shown in pLTA-injected ApoE(-/-) mice, which was concurrent with inhibition of MMP-9 and preservation of CD31 production. The antiinflammatory effect mediated by pLTA decreased expression of atherosclerotic markers such as COX-2, Bax, and HSP27 and also cell surface receptors such as TLR4 and CCR7. Together, these results underscore the role of pLTA in suppressing atherosclerotic plaque inflammation and will help in identifying targets with therapeutic potential against pathogen-mediated atherogenesis.

Evaluation of the mydriatic effect of intracameral lidocaine hydrochloride injection in eyes of clinically normal dogs.

OBJECTIVE-To evaluate the mydriatic effect of intracameral injection of preservative-free 1% and 2% lidocaine hydrochloride solutions and determine the onset and duration of mydriasis according to the concentration and volume of lidocaine administered in healthy dogs. ANIMALS-5 healthy adult Beagles weighing 7 to 10 kg, with no apparent ocular disease. PROCEDURES-A double-blind randomized 9-session crossover trial was designed. Both eyes were assigned to 9 treatments with a minimum 7-day washout period between treatments: 0.1, 0.2, and 0.3 mL of 2% lidocaine solution; 0.1, 0.2, and 0.3 mL of 1% lidocaine solution; and 0.1, 0.2, and 0.3 mL of balanced salt solution. Dogs were anesthetized, and the allocated treatment was injected intracamerally after aspiration of the same volume of aqueous humor from the anterior chamber of each eye. Two perpendicular pupil diameters were measured. Intraocular pressure, heart rate, respiratory rate, ECG readings, and end-tidal partial pressure of CO(2) were monitored. RESULTS-Intracameral injection of 1% or 2% lidocaine solutions in volumes of 0.1 to 0.3 mL induced a significant degree of mydriasis, and the effect was maintained for 74 to 142 minutes. Lidocaine injection had no significant effect on intraocular pressure, heart rate, respiratory rate, ECG readings, or end-tidal partial pressure of CO(2). CONCLUSIONS AND CLINICAL RELEVANCE-Intracameral lidocaine injection in healthy dogs induced mydriasis, the timing of which was affected by concentration and volume of lidocaine. This technique could serve as an alternative to topically administered mydriatics for intraocular surgery in dogs.

Inhibitory effects of Lactobacillus plantarum lipoteichoic acid (LTA) on Staphylococcus aureus LTA-induced tumor necrosis factor-alpha production.

Staphylococcus aureus is a common etiologic agent for Gram-positive sepsis, and its lipoteichoic acid (LTA) may be important in causing Gram-positive bacterial septic shock. Here, we demonstrate that highly purified LTA (pLTA) isolated from Lactobacillus plantarum inhibited aureus LTA (aLTA)-induced TNF-alpha production in THP- cells. Whereas pLTA scarcely induced TNF-alpha production, aLTA induced excessive TNF-alpha production. Interestingly, aLTA-induced TNF-alpha production was inhibited by pLTA pretreatment. Compared with pLTA, aLTA induced strong signal transduction through the MyD88, NF-kappaB, and MAP kinases. This signaling, however, was reduced by a pLTA pretreatment, and resulted in the inhibition of aLTA-induced TNF-alpha production. Whereas dealanylated LTAs, as well as native LTAs, contributed to TNF- induction or TNF-alpha reduction, deacylated LTAs did not, indicating that the acyl chain of LTA played an important role in the LTA-mediated immune regulation. These results suggest that pLTA may act as an antagonist for aLTA, and that an antagonistic pLTA may be a useful agent for suppressing the septic shock caused by Gram-positive bacteria.

Lipoteichoic acid isolated from Lactobacillus plantarum inhibits lipopolysaccharide-induced TNF-alpha production in THP-1 cells and endotoxin shock in mice.

In this study, the effect of Lactobacillus plantarum lipoteichoic acid (pLTA) on LPS-induced MAPK activation, NF-kappaB activation, and the expression of TNF-alpha and IL-1R-associated kinase M (IRAK-M) was examined. The expression of the pattern recognition receptor and the survival rate of mice were also examined. pLTA pretreatment inhibited the phosphorylation of ERK, JNK, and p38 kinase. It also inhibited the degradation of IkappaBalpha and IkappaBbeta, as well as the activation of the LPS-induced TNF-alpha factor in response to subsequent LPS stimulation. These changes were accompanied by the suppression of the LPS-induced expression of TLR4, NOD1, and NOD2, and the induction of IRAK-M, with a concurrent reduction of TNF-alpha secretion. Furthermore, the overexpression of pattern recognition receptors such as TLR4, NOD1, and NOD2 and the degradation of IRAK-M by transient transfection were found to reinstate the production of TNF-alpha after LPS restimulation. In addition, the i.p. injection of pLTA suppressed fatality, and decreased the level of TNF-alpha in the blood, in LPS-induced endotoxin shock mice. In conclusion, these data extend our understanding of the pLTA tolerance mechanism, which is related to the inhibition of LPS-induced endotoxin shock, and suggest that pLTA may have promise as a new therapeutic agent for LPS-induced septic shock.