Deep learning detection of hand motion during microvascular anastomosis simulations performed by expert cerebrovascular neurosurgeons.

OBJECTIVE: Deep learning enables precise hand tracking without the need for physical sensors, allowing for unsupervised quantitative evaluation of surgical motion and tasks. We quantitatively assessed the hand motions of experienced cerebrovascular neurosurgeons during simulated microvascular anastomosis using deep learning. We explored the extent to which surgical motion data differed among experts. METHODS: A deep learning detection system tracked 21 landmarks corresponding to digit joints and the wrist on each hand of 5 expert cerebrovascular neurosurgeons. Tracking data for each surgeon was analyzed over long and short time intervals to examine gross movements and micromovements, respectively. Quantitative algorithms assessed the economy and flow of motion by calculating mean movement distances from the baseline median landmark coordinates and median times between sutures, respectively. RESULTS: Tracking data correlated with specific surgical actions observed in microanastomosis video analysis. Economy of motion during suturing was calculated as 19, 26, 29, 27, and 28 pixels for surgeons 1, 2, 3, 4, and 5, respectively. Flow of motion during microanastomosis was 31.96, 29.40, 28.90, 7.37, and 47.21 secs for surgeons 1, 2, 3, 4, and 5, respectively. CONCLUSIONS: Hand tracking data showed similarities among experts, with low movements from baseline, minimal excess motion, and rhythmic suturing patterns. The data revealed unique patterns related to each expert's habits and techniques. The results showed that surgical motion can be correlated with hand motion and assessed using mathematical algorithms. We also demonstrated the feasibility and potential of deep learning-based motion detection to enhance surgical training.

Impacts of tolylfluanid on implantation and placental development: Disruption of mitochondrial function and implantation-related gene expression in vitro and in vivo.

Tolylfluanid is a widely used pesticide and antifouling agent in agricultural and marine industries and is recognized as a potential endocrine disruptor. However, the toxicological effects of tolylfluanid on the placenta development was not elucidated. This study used trophoblastic cell (HTR-8/SVneo cell) and endometrial cell (T HESCs) lines as in vitro model and mouse models as in vivo model to investigate the toxic effects of tolylfluanid on implantation-associated cell and placenta development during early pregnancy. Experimental results indicated that both cell lines exhibited reduced viability upon tolylfluanid exposure. Various in vitro experiments were conducted at <1 mg/L concentration. The results indicate that tolylfluanid can arrest cell cycle and induce apoptosis in endometrial and trophoblastic cells, abnormally regulate Ca2+ homeostasis and MAPK signaling pathways, and disrupt mitochondrial function. In vivo experiments, subchronic tolylfluanid exposure to mouse during puberty and pregnancy period impaired placenta development, resulting in reduced fetal and placental weight, abnormal placental structures, and altered gene expression. Specifically, a decrease in the ratio of labyrinth/junctional zones and changes in placenta gene expression patterns after tolylfluanid exposure were similar to characters of adverse pregnancy outcomes such as preeclampsia and fetal growth restriction (FGR). This study suggests that tolylfluanid exposure may have negative outcomes on female reproduction, and highlights the need for stricter regulation and monitoring of tolylfluanid use to protect women's reproductive health. This is the first study indicating the adverse effects of tolylfluanid on implantation and placental development during pregnancy.

Therapeutic effects of S-allyl-L-cysteine in a mouse endometriosis model and its immunomodulatory effects via regulation of T cell subsets and cytokine expression.

BACKGROUND: Endometriosis is a female hormone-dependent gynecological disorder characterized by chronic inflammation. Therefore, the development of novel treatment strategies that can diminish the side effects of the long-term use of hormone-based drugs has been emphasized. S-Allyl-L-cysteine (SAC) is the major constituent of aged garlic extracts. Although the therapeutic effects resulting from the antioxidant properties of SAC have been extensively studied in inflammatory diseases, the therapeutic efficacy of SAC in endometriosis has not been described. In this study, we investigated the therapeutic potential of SAC for endometriosis using a mouse model. METHODS: An endometriosis mouse model was surgically induced, and oral treatment with 30 mg/kg SAC was administered daily for 28 days. The development of endometriotic lesions was assessed by histological analysis, and the expression profiles of adhesion-, apoptosis-, and inflammation-related genes were evaluated by PCR. Flow cytometric analysis of mouse spleen was conducted to assess changes in lymphocyte subpopulations. RESULTS: SAC treatment significantly inhibited endometriotic lesion growth. Transcriptional expression analysis revealed the antiadhesion and apoptosis-promoting effects of SAC. In particular, SAC showed an effective immune modulatory response by altering splenic CD4+ and CD8+ T cell subsets and inflammatory cytokine production in the spleen and endometriotic lesions. CONCLUSION: This study newly elucidates the inhibitory effects of SAC on the growth of endometriosis in a mouse model and describes its immunomodulatory effects.

Computational image analysis of distortion, sharpness, and depth of field in a next-generation hybrid exoscopic and microsurgical operative platform.

Objective: The development of surgical microscope-associated cameras has given rise to a new operating style embodied by hybrid microsurgical and exoscopic operative systems. These platforms utilize specialized camera systems to visualize cranial neuroanatomy at various depths. Our study aims to understand how different camera settings in a novel hybrid exoscope system influence image quality in the context of neurosurgical procedures. Methods: We built an image database using captured cadaveric dissection images obtained with a prototype version of a hybrid (microsurgical/exoscopic) operative platform. We performed comprehensive 4K-resolution image capture using 76 camera settings across three magnification levels and two working distances. Computer algorithms such as structural similarity (SSIM) and mean squared error (MSE) were used to measure image distortion across different camera settings. We utilized a Laplacian filter to compute the overall sharpness of the acquired images. Additionally, a monocular depth estimation deep learning model was used to examine the image's capability to visualize the depth of deeper structures accurately. Results: A total of 1,368 high-resolution pictures were captured. The SSIM index ranged from 0.63 to 0.85. The MSE was nearly zero for all image batches. It was determined that the exoscope could accurately detect both the sharpness and depth based on the Laplacian filter and depth maps, respectively. Our findings demonstrate that users can utilize the full range of camera settings available on the exoscope, including adjustments to aperture, color saturation, contrast, sharpness, and brilliance, without introducing significant image distortions relative to the standard mode. Conclusion: The evolution of the camera incorporated into a surgical microscope enables exoscopic visualization during cranial base surgery. Our result should encourage surgeons to take full advantage of the exoscope's extensive range of camera settings to match their personal preferences or specific clinical requirements of the surgical scenario. This places the exoscope as an invaluable asset in contemporary surgical practice, merging high-definition imaging with ergonomic design and adaptable operability.

Assessing accuracy and consistency in intracranial aneurysm sizing: human expertise vs. artificial intelligence.

Intracranial aneurysms (IAs) are a common vascular pathology and are associated with a risk of rupture, which is often fatal. Aneurysm growth of more than 1 mm is considered a surrogate of rupture risk, therefore, this study presents a comprehensive analysis of intracranial aneurysm measurements utilizing a dataset comprising 358 IA from 248 computed tomography angiography (CTA) scans measured by four junior raters and one senior rater. The study explores the variability in sizing assessments by employing both human raters and an Artificial Intelligence (AI) system. Our findings reveal substantial inter- and intra-rater variability among junior raters, contrasting with the lower intra-rater variability observed in the senior rater. Standard deviations of all raters were above the threshold for IA growth (1 mm). Additionally, the study identifies a systemic bias, indicating a tendency for human experts to measure aneurysms smaller than the AI system. Our findings emphasize the challenges in human assessment while also showcasing the capacity of AI technology to improve the precision and reliability of intracranial aneurysm assessments, especially beneficial for junior raters. The potential of AI was particularly evident in the task of monitoring IA at various intervals, where the AI-based approach surpassed junior raters and achieved performance comparable to senior raters.

Ventriculoperitoneal shunt infection and malfunction in adult patients: incidence, risk factors, and long-term follow-up of single institution experience.

Ventriculoperitoneal shunt surgery was developed to manage excessive cerebrospinal fluid (CSF) in the brain's ventricles and is considered a mainstream treatment. Despite the development of the shunt device system, various complications still occur. In this study, we reported 307 cases and a long-term follow-up of at least five years of adult patients who underwent VP shunt surgery and analyzed various factors that may affect revision surgery. A retrospective study was conducted at Asan Medical Center, Korea, a tertiary medical center. We reviewed 307 cases from January 2012 to December 2018. The patients' neurological status, predisposing medical conditions, laboratory findings, and other operation-related factors were reviewed using electrical medical records. The normal function group comprised 272 cases (88.6%), and the overall incidence of revision group comprised 35 cases (11.4%). Of the 35 revision surgery cases, 30 (85.71%) were due to shunt malfunctions, such as obstruction, overdrainage, and valve-related errors while 5 (14.29%) were due to shunt infection. Patient demographics, mental status, and operation time did not influence revision as risk factors. Serum laboratory findings showed no statistical difference between the two groups. The white blood cell (WBC) count in the CSF profile differed significantly between the two groups. The Hakim Programmable valve (Codman, USA) is mainly used in our center. In addition, various shunt systems were used, including Strata Regulatory valve (Medtronic, USA), proGAV (Aesculap, USA), and Accu-Flo (Codman, USA). This study analyzed the factors affecting long-term outcomes. Based on these findings, efforts are needed to achieve more favorable outcomes in the future.

Therapeutic efficacy and anti-inflammatory mechanism of baicalein on endometriosis progression in patient-derived cell line and mouse model.

BACKGROUND: Baicalein is a flavonoid extracted from the roots of Scutellaria baicalensis G. that has anti-inflammatory and antitumor effects. However, therapeutic mechanisms of baicalein in patients with endometriosis in vivo have yet to be elucidated. As a chronic inflammatory gynecological disease, endometriosis causes pain and infertility, and has no complete treatment to date. Current treatment strategies cause several side effects and have high recurrence rates. PURPOSE: This study aimed to identify the in vivo therapeutic effects of baicalein on endometriosis and verify the action mechanisms of baicalein, focusing on regulating inflammation. METHODS: In this study, an autologous transplant mouse model and patient-derived immortalized human ovarian endometriotic stromal cells (ihOESCs) were used to investigate the therapeutic activities of baicalein. The mouse model was administered with 40 mg/kg baicalein by oral gavage for 4 weeks, and the treatment outcomes of baicalein-treated mice were compared with vehicle- and dienogest-treated groups. ihOESCs were treated with 0-5 µg/ml baicalein for in vitro studies. RESULTS: Baicalein significantly alleviated the progression of endometriosis in mouse models. Baicalein reduced the expression of proinflammatory cytokines in endometriotic lesions and ihOESCs, and cytokine expression and T cell proportions in mouse spleen. in vitro results showed that baicalein increased mitochondrial calcium flux and induced mitochondrial depolarization and ROS generation in ihOESCs. Ultimately, baicalein inactivated the MAPK/PI3K signaling and induced cell death in ihOESCs. CONCLUSION: In conclusion, baicalein effectively attenuated the progression of endometriosis through its anti-inflammatory activities. Baicalein can be an alternative or supplemental treatment for endometriosis to ameliorate the side effects of hormonal therapy.

The efficacy of therapeutic hypothermia in patients with poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

BACKGROUND: This study evaluates the effectiveness of Therapeutic Hypothermia (TH) in treating poor-grade aneurysmal subarachnoid hemorrhage (SAH), focusing on functional outcomes, mortality, and complications such as vasospasm, delayed cerebral ischemia (DCI), and hydrocephalus. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive literature search was conducted across multiple databases, including Medline, Embase, and Cochrane Central, up to November 2023. Nine studies involving 368 patients were selected based on eligibility criteria focusing on TH in poor-grade SAH patients. Data extraction, bias assessment, and evidence certainty were systematically performed. RESULTS: The primary analysis of unfavorable outcomes in 271 participants showed no significant difference between the TH and standard care groups (risk ratio [RR], 0.87). However, a significant reduction in vasospasm was observed in the TH group (RR, 0.63) among 174 participants. No significant differences were found in DCI, hydrocephalus, and mortality rates in the respective participant groups. CONCLUSIONS: TH did not significantly improve primary unfavorable outcomes in poor-grade SAH patients. However, the reduction in vasospasm rates indicates potential specific benefits. The absence of significant findings in other secondary outcomes and mortality highlights the need for further research to better understand TH's role in treating this patient population.

Treatment Strategy of Unruptured Intracranial Aneurysms in Octogenarian Patients: A Single-Institution Experience.

AIM: To share our clinical insights into octogenarian patients with unruptured intracranial aneurysms (UIAs) and evaluate the treatment strategies for this demographic. MATERIAL AND METHODS: A retrospective analysis was conducted on data from 134 patients with a follow-up exceeding 6 months, all enrolled in this study. We assessed the incidence rates (IRs) of aneurysm growth and rupture, along with potential predictors of aneurysm growth. RESULTS: Among the 134 patients, 99 (73.9%) underwent conservative management, 25 (18.7%) received coiling, and 10 (7.5%) underwent clipping. The mean age of the cohort was 81.8 years. The middle cerebral artery was the most common location for aneurysms. The mean aneurysm size was 4.9 mm, with sizes significantly larger in the treatment groups (coiling and clipping) compared to the observation group (4.4 mm in the observation group; 5.9 and 7.4 mm in the coiling and clipping groups, respectively). The proportion of aneurysms with a daughter sac was higher in the treatment groups compared to the observation group (6.1% vs. 44% [coiling] and 50% [clipping]). The IR of aneurysm growth was 5.9 per 100 person-years, and that of aneurysm rupture was 0.8 per 100 person-years. No factors were statistically significant for aneurysm growth. CONCLUSION: Age alone, especially in individuals over 80 years old, may not be a contraindication for UIA treatment. We recommend considering treatment in octogenarians with high-risk aneurysm features, such as a large aneurysm and the presence of a daughter sac, as the complication rates are low.

Treatment of conus medullaris arteriovenous malformation: the role of microsurgical treatment.

OBJECTIVE: Conus medullaris arteriovenous malformation (AVM) is rare and challenging to treat. To better define the presentation, prognosis, and optimal treatment of these lesions, the authors present their treatment experiences for conus medullaris AVM. METHODS: Eleven patients with AVM of the conus medullaris were identified between March 2013 and December 2021. Among these patients, 7 who underwent microsurgical treatment were included. Patient data, including age, sex, symptoms at presentation, neurological status, radiological findings, nidus depth (mainly pial lesion vs intramedullary lesion), type of treatment, and recurrence at follow-up, were collected. Postoperative angiography was performed in all patients. Spinal cord function was evaluated using the Frankel grade at the time of admission and 1 year after surgery. RESULTS: All 7 patients presenting with myeloradiculopathy were treated surgically. Four patients (57.1%) underwent endovascular embolization, followed by resection. The other 3 patients underwent microsurgery only. Complete occlusion was confirmed with postoperative angiography in all patients. Of the 3 patients who were nonambulatory before surgery (Frankel grade C), 2 were able to walk after surgery (Frankel grade D) and 1 remained nonambulatory (Frankel grade C) at 1-year follow-up. CONCLUSIONS: Based on the authors' clinical experiences, the results of multimodal treatment for conus medullaris AVM are good, with microsurgical treatment playing an important role. The microsurgical strategy can differ depending on the location of the nidus, and when possible, good results can be expected through microsurgical resection.

Risk of Cerebral Aneurysm Rupture After Liver Transplantation: Development and Validation of a Hemorrhagic Stroke Scoring Model.

BACKGROUND: Liver transplantation (LT) patients appear to be more prone to neurological events compared to individuals undergoing other types of solid-organ transplantation. The aims of the present study were to analyze the prevalence of unruptured intracranial aneurysms (UIAs) in patients undergoing liver transplantation (LT) and to examine the perioperative occurrence of subarachnoid hemorrhage (SAH). Also, it intended to systematically identify the risk factors of SAH and hemorrhagic stroke (HS) within a year after LT and to develop a scoring system which involves distinct clinical features of LT patients. METHODS: Patients who underwent LT from January 2012 to March 2022 were analyzed. All included patients underwent neurovascular imaging within 6 months before LT. We conducted an analysis of prevalence and radiological features of UIA and SAH. The clinical factors that may have an impact on HS within one year of LT were also reviewed. RESULTS: Total of 3,487 patients were enrolled in our study after applying inclusion and exclusion criteria. The prevalence of UIA was 5.4%. The incidence of SAH and HS within one year following LT was 0.5% and 1.6%, respectively. We developed a scoring system based on multivariable analysis to predict the HS within 1-year after LT. The variables were a poor admission mental status, the diagnosis of UIA, serum ammonia levels, and Model for End-stage Liver Disease (MELD) scores. Our model showed good discrimination among the development (C index, 0.727; 95% confidence interval [CI], 0.635-0.820) and validation (C index, 0.719; 95% CI, 0.598-0.801) cohorts. CONCLUSION: The incidence of UIA and SAH was very low in LT patients. A poor admission mental status, diagnosis of UIA, serum ammonia levels, and MELD scores were significantly associated with the risk of HS within one year after LT. Our scoring system showed a good discrimination to predict the HS in LT patients.

Meptyldinocap induces implantation failure by forcing cell cycle arrest, mitochondrial dysfunction, and endoplasmic reticulum stress in porcine trophectoderm and endometrial luminal epithelial cells.

Meptyldinocap is a dinitrophenol fungicide used to control powdery mildew. Although other dinitrophenol pesticides have been found to exhibit reproductive toxicity, studies of meptyldinocaps are scarce. This study investigated the adverse effects of meptyldinocap on porcine trophectoderm (pTr) and porcine endometrial luminal epithelial (pLE) cells, which play crucial roles in implantation. We confirmed that meptyldinocap decreased cell viability, induced apoptosis, and inhibited proliferation by decreasing proliferation-related gene expression and inducing changes in the cell cycle. Furthermore, meptyldinocap treatment caused mitochondrial dysfunction, endoplasmic reticulum stress, and disruption of calcium homeostasis. Moreover, it induces alterations in mitogen-activated protein kinase signaling cascades and reduces the migration ability, leading to implantation failure. Our findings suggest that meptyldinocap reduces the cellular functions of pTr and pLE cells, which are important for the implantation process, and interferes with interactions between the two cell lines, potentially leading to implantation failure. We also propose a mechanism by which the understudied fungicide meptyldinocap exerts its cytotoxicity.

Hexaconazole induces developmental toxicities via apoptosis, inflammation, and alterations of Akt and MAPK signaling cascades.

Hexaconazole is a highly effective triazole fungicide that is frequently applied in various countries to elevate crop productivity. Given its long half-life and high water solubility, this fungicide is frequently detected in the environment, including water sources. Moreover, hexaconazole exerts hazardous effects on nontarget organisms. However, little is known about the toxic effects of hexaconazole on animal development. Thus, this study aimed to investigate the developmental toxicity of hexaconazole to zebrafish, a valuable animal model for toxicological studies, and elucidate the underlying mechanisms. Results showed that hexaconazole affected the viability and hatching rate of zebrafish at 96 h postfertilization. Hexaconazole-treated zebrafish showed phenotypic defects, such as reduced size of head and eyes and enlarged pericardiac edema. Moreover, hexaconazole induced apoptosis, DNA fragmentation, and inflammation in developing zebrafish. Various organ defects, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity, were observed in transgenic zebrafish models olig2:dsRed, fli1:eGFP, and l-fabp:dsRed. Furthermore, hexaconazole treatment altered the Akt and MAPK signaling pathways, which possibly triggered the organ defects and other toxic mechanisms. This study demonstrated the developmental toxicity of hexaconazole to zebrafish and elucidated the underlying mechanisms.

The efficacy of surgical site suction drain insertion in pterional craniotomy for intracranial cerebral aneurysm.

Objective: We evaluated the role of subgaleal closed suction drains in postoperative epidural hematoma (EDH) and wound complications following pterional craniotomy for cerebral aneurysm. Methods: We reviewed 5,280 pterional craniotomies performed on 5,139 patients between January 2006 and December 2020. A drain was placed subgalealy and tip of drain was positioned between the bone flap and the deep temporalis. 1,637 cases (31%) had a subgaleal suction drain. We analyzed demographic and clinical variables related to EDH requiring evacuation and wound complications in patients with and without drains. Univariate and multivariate logistic regression analyses were performed to determine the associated risk factors. Results: Fourteen cases (0.27%) of EDH requiring evacuation and 30 cases (0.57%) of wound complications were identified. Univariate analysis found that drain insertion, subarachnoid hemorrhage (SAH), and operation time were associated with EDH, while drain insertion, SAH, male gender, older age, and longer operation time were associated with wound complications. Multivariate analysis found no significant association between drain use and EDH (OR=1.62, p=0.402) or wound complications (OR=1.45, p=0.342). Conclusions: Routine use of subgaleal closed suction drains may not be necessary after pterional craniotomy, as drain insertion was not associated with a reduced risk of EDH requiring evacuation or wound complications.

Alteration in Effects of Endometriosis on Fecundity According to Pregnancy Experience in Mouse Model.

This study is aimed at identifying variations in the effect of endometriosis on fecundity in a mouse model based on prior pregnancy experience. Endometriosis is one of the most prevalent gynecological diseases and is known to impact female fecundity adversely. In this study, an endometriosis mouse model was established by allografting uterine horn tissue using Pelch's method. The effect of endometriosis on fecundity was confirmed in primiparous and multiparous female mice. As fecundity indicators, the pregnancy rate, number of litters, pregnancy period, and survival rate of the pups were investigated. As a result of the experiment, the pregnancy rate decreased, and the pregnancy period tended to be shorter in primiparous female mice. However, there was no significant change in the multiparous mice. In addition, it has been established that correlations exist between the size of lesions and certain fecundity indicators of the lesion, even among primiparous and multiparous females with endometriosis. The study attempted to demonstrate a link between pregnancy experience and fecundity changes caused by endometriosis by experimentally reproducing clinical results using mouse models. These results suggest strategies for identifying several pathophysiological characteristics of endometriosis.

Pyridaben induces apoptosis and inflammation in bovine mammary epithelial cells by disturbance of calcium homeostasis and upregulation of MAPK cascades.

Pyridaben is a widely used pyridazinone insecticide used to protect crops against insects and mites. The toxicity of pyridaben has been reported in mice, zebrafish, the human reproductive system, nervous system, and respiratory system. Pyridaben can also be ingested by dairy cattle through feed. However, the toxicity of pyridaben in cattle has not been investigated on. Thus, this study focuses on demonstrating the toxicity of pyridaben in the bovine mammary glands and with the generation milk in the bovine mammary epithelial cells, as it is crucial to the continuance of the amount and the quality of the milk produced. We started by analyzing the intracellular toxicity along with the impact of pyridaben on the cell cycle distribution and the transcription of associated genes. Pyridaben treatment induced cell cycle arrest accompanied the disruption in G1 and S phases with imbalanced cytosolic and mitochondrial calcium ion homeostasis, and caused a destruction of mitochondrial membrane potential. This eventually led to apoptosis of MAC-T cells. We also investigated in the impact that pyridaben has on MAPK signaling proteins, where phosphorylation of ERK1/2, JNK, and p38 were upregulateed. Moreover, examination of the effect of pyridaben in the inflammatory genes revealed hyperactivation of the inflammatory gene transcription. This is the first research to assess the negative outcomes that pyridaben could impose on dairy cattle and milk production.

Chemical and perfusion markers as predictors of moyamoya disease progression and complication types.

To investigate the association between chemical markers (triglyceride, C-reactive protein (CRP), and inflammation markers) and perfusion markers (relative cerebral vascular reserve (rCVR)) with moyamoya disease progression and complication types. A total of 314 patients diagnosed with moyamoya disease were included. Triglyceride and CRP levels were assessed and categorized based on Korean guidelines for dyslipidemia and CDC/AHA guidelines, respectively. Perfusion markers were evaluated using Diamox SPECT. Cox proportional hazard analysis was performed to examine the relationship between these markers and disease progression, as well as complication types (ischemic stroke, hemorrhagic stroke, and rCVR deterioration). Elevated triglyceride levels (≥ 200) were significantly associated with higher likelihood of end-point events (HR: 2.292, CI 1.00-4.979, P = 0.03). Severe decreased rCVR findings on Diamox SPECT were also significantly associated with end-point events (HR: 3.431, CI 1.254-9.389, P = 0.02). Increased CRP levels and white blood cell (WBC) count were significantly associated with moyamoya disease progression. For hemorrhagic stroke, higher triglyceride levels were significantly associated with end-point events (HR: 5.180, CI 1.355-19.801, P = 0.02). For ischemic stroke, severe decreased rCVR findings on Diamox SPECT (HR: 5.939, CI 1.616-21.829, P < 0.01) and increased CRP levels (HR: 1.465, CI 1.009-2.127, P = 0.05) were significantly associated with end-point events. Elevated triglyceride, CRP, and inflammation markers, as well as decreased rCVR, are potential predictors of moyamoya disease progression and complication types. Further research is warranted to understand their role in disease pathophysiology and treatment strategies.

Osthole impairs mitochondrial metabolism and the autophagic flux in colorectal cancer.

BACKGROUND: Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the regulatory activity of osthole in colorectal cancer development, focusing on mitochondrial metabolism, is not well known. HYPOTHESIS/PURPOSE: We hypothesized that osthole may suppress progression of colorectal cancer and aimed to determine the underlying mitochondrial metabolism and the autophagic flux. STUDY DESIGN: In this study, we elucidated the mechanism of action of osthole in colorectal cancer using an in vivo azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model and an in vitro cell culture system. METHODS: AOM/DSS mouse model was established and analyzed the effects of osthole on survival rate, diseases activity index, number of tumor and histopathology. Then, cell based assays including viability, cell cycle, reactive oxygen species (ROS), apoptosis, calcium efflux, and mitochondrial function were analyzed. Moreover, osthole-mediated signaling was demonstrated by western blot analyses. RESULTS: Osthole effectively suppressed the growth of colorectal tumors and alleviated AOM/DSS-induced intestinal injury. Osthole restored the function of goblet cells and impaired the expression of Claudin1 and Axin1 impaired by AOM/DSS. In addition, osthole specifically showed cytotoxicity in colorectal carcinoma cells, but not in normal colon cells. Osthole decreased the ASC/caspase-1/IL-1ß inflammasome pathway and induced mitochondrial dysfunction in redox homeostasis, calcium homeostasis. Furthermore, osthole inhibited both oxidative phosphorylation (OXPHOS) and glycolysis, leading to the suppression of ATP production. Moreover, via combination treatment with chloroquine (CQ), we demonstrated that osthole impaired autophagic flux, leading to apoptosis of HCT116 and HT29 cells. Finally, we elucidated that the functional role of tiRNAHisGTG regulated by osthole directly affects the cellular fate of colon cancer cells. CONCLUSION: These results suggest that osthole has the potential to manage progression of colorectal cancer by regulating autophagy- and mitochondria-mediated signal transduction.

Fraxetin reduces endometriotic lesions through activation of ER stress, induction of mitochondria-mediated apoptosis, and generation of ROS.

BACKGROUND: Fraxetin, a phytochemical obtained from Fraxinus rhynchophylla, is well known for its anti-inflammatory and anti-fibrotic properties. However, fraxetin regulates the progression of endometriosis, which is a benign reproductive disease that results in low quality of life and infertility. HYPOTHESIS/PURPOSE: We hypothesized that fraxetin may have therapeutic effects on endometriosis and aimed to elucidate the underlying mechanisms of mitochondrial function and tiRNA regulation. STUDY DESIGN: Endometriotic animal models and cells (End1/E6E7 and VK2/E6E7) were used to identify the mode of action of fraxetin. METHODS: An auto-implanted endometriosis animal model was established and the effects of fraxetin on lesion size reduction were analyzed. Cell-based assays including proliferation, cell cycle, migration, apoptosis, mitochondrial function, calcium efflux, and reactive oxygen species (ROS) were performed. Moreover, fraxetin signal transduction was demonstrated by western blotting and qPCR analyses. RESULTS: Fraxetin inhibited proliferation and migration by inactivating the P38/JNK/ERK mitogen-activated protein kinase (MAPK) and AKT/S6 pathways. Fraxetin dissipates mitochondrial membrane potential, downregulates oxidative phosphorylation (OXPHOS), and disrupts redox and calcium homeostasis. Moreover, it triggered endoplasmic reticulum stress and intrinsic apoptosis. Furthermore, we elucidated the functional role of tiRNAHisGTG in endometriosis by transfection with its inhibitor. Finally, we established an endometriosis mouse model and verified endometriotic lesion regression and downregulation of adhesion molecules with inflammation. CONCLUSION: This study suggests that fraxetin is a novel therapeutic agent that targets mitochondria and tiRNAs. This is the first study to demonstrate the mechanisms of tiRNAHisGTG with mitochondrial function and cell fates and can be applied as a non-hormonal method against the progression of endometriosis.