Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria.

BACKGROUND/AIM: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. METHODS: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. RESULTS: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). CONCLUSIONS: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

Array-wide uniform PEDOT:PSS electroplating from potentiostatic deposition.

Electroplating of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is important in many neuroelectronic applications but is challenging to achieve uniformity on large-scale microelectrode arrays (MEA) using conventional galvanostatic methods. In this study, we address this challenge through a potentiostatic method and demonstrate highly uniform electroplating of PEDOT:PSS on MEA with more than one hundred electrodes, all at cellular sizes. The validation of this approach involves comparisons with galvanostatic deposition methods, showcasing unparalleled deposition yield and uniformity. Systematic electrochemical characterizations reveal similarities in structure and stability from potentiostatic deposited coatings. The advances developed here establish the potentiostatic method and detailed process to achieve a uniform coating of PEDOT:PSS on large-scale MEA, with broad utility in neuroelectronics.

Improved Diagnostic Accuracy of Thyroid Fine-Needle Aspiration Cytology with Artificial Intelligence Technology.

Background: Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images (WSIs) of thyroid fine-needle aspiration cytology (FNA), incorporating z-stacking, from institutions across the nation to develop an AI model. Methods: We conducted a multicenter retrospective diagnostic accuracy study using thyroid FNA dataset from the Open AI Dataset Project that consists of digitalized images samples collected from 3 university hospitals and 215 Korean institutions through extensive quality check during the case selection, scanning, labeling, and reviewing process. Multiple z-layer images were captured using three different scanners and image patches were extracted from WSIs and resized after focus fusion and color normalization. We pretested six AI models, determining Inception ResNet v2 as the best model using a subset of dataset, and subsequently tested the final model with total datasets. Additionally, we compared the performance of AI and cytopathologists using randomly selected 1031 image patches and reevaluated the cytopathologists' performance after reference to AI results. Results: A total of 10,332 image patches from 306 thyroid FNAs, comprising 78 malignant (papillary thyroid carcinoma) and 228 benign from 86 institutions were used for the AI training. Inception ResNet v2 achieved highest accuracy of 99.7%, 97.7%, and 94.9% for training, validation, and test dataset, respectively (sensitivity 99.9%, 99.6%, and 100% and specificity 99.6%, 96.4%, and 90.4% for training, validation, and test dataset, respectively). In the comparison between AI and human, AI model showed higher accuracy and specificity than the average expert cytopathologists beyond the two-standard deviation (accuracy 99.71% [95% confidence interval (CI), 99.38-100.00%] vs. 88.91% [95% CI, 86.99-90.83%], sensitivity 99.81% [95% CI, 99.54-100.00%] vs. 87.26% [95% CI, 85.22-89.30%], and specificity 99.61% [95% CI, 99.23-99.99%] vs. 90.58% [95% CI, 88.80-92.36%]). Moreover, after referring to the AI results, the performance of all the experts (accuracy 96%, 95%, and 96%, respectively) and the diagnostic agreement (from 0.64 to 0.84) increased. Conclusions: These results suggest that the application of AI technology to thyroid FNA cytology may improve the diagnostic accuracy as well as intra- and inter-observer variability among pathologists. Further confirmatory research is needed.

Immunoglobulin G4-related disease mimicking an appendiceal neoplasm: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies.

Aortic Angiosarcoma Manifesting as Multiple Musculoskeletal Metastases: A Case Report.

Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases. A 59-year-old male patient presented with left thigh pain. Plain radiographs revealed multifocal osteolytic lesions in the left femur shaft. Abdominopelvic computed tomography showed a lobulated osteolytic lesion in the left iliac bone. Magnetic resonance images revealed multifocal soft tissue lesions in the thigh musculature. A positron emission tomography/computed tomography (PET/CT) scan demonstrated multiple foci of increased uptake in the left femur bone, pelvis, left thigh, and calf musculature. Focal increased uptake in the lower abdominal aorta was newly detected. Pelvis biopsy showed tumor cell nests of epithelioid cells. The tumor cells showed vasoformative features. Immunohistochemically, the tumor cells showed positivity for vimentin, CD31, and ERG. The pathologic diagnosis of epithelioid angiosarcoma was established. The origin of the tumor was presumed to be the aorta. This case underscores the importance of PET scans in identifying primary lesions. In terms of the histopathologic diagnosis of biopsy samples with tumor cells exhibiting epithelioid neoplastic morphology, employing appropriate ancillary techniques such as immunocytochemistry with vascular markers may assist in accurately diagnosing metastatic angiosarcoma.

Artificial-Intelligence-Assisted Detection of Metastatic Colorectal Cancer Cells in Ascitic Fluid.

Ascites cytology is a cost-effective test for metastatic colorectal cancer (CRC) in the abdominal cavity. However, metastatic carcinoma of the peritoneum is difficult to diagnose based on biopsy findings, and ascitic aspiration cytology has a low sensitivity and specificity and a high inter-observer variability. The aim of the present study was to apply artificial intelligence (AI) to classify benign and malignant cells in ascites cytology patch images of metastatic CRC using a deep convolutional neural network. Datasets were collected from The OPEN AI Dataset Project, a nationwide cytology dataset for AI research. The numbers of patch images used for training, validation, and testing were 56,560, 7068, and 6534, respectively. We evaluated 1041 patch images of benign and metastatic CRC in the ascitic fluid to compare the performance of pathologists and an AI algorithm, and to examine whether the diagnostic accuracy of pathologists improved with the assistance of AI. This AI method showed an accuracy, a sensitivity, and a specificity of 93.74%, 87.76%, and 99.75%, respectively, for the differential diagnosis of malignant and benign ascites. The diagnostic accuracy and sensitivity of the pathologist with the assistance of the proposed AI method increased from 86.8% to 90.5% and from 73.3% to 79.3%, respectively. The proposed deep learning method may assist pathologists with different levels of experience in diagnosing metastatic CRC cells of ascites.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a good prognostic marker for pancreatic/periampullary cancers.

BACKGROUND: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerases-1 (PARP-1) have emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well. METHODS: We assessed the prognostic significance of PARP1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray. RESULTS: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers (P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses (P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers. CONCLUSIONS: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.

Post-COVID-19 Vaccination Myocarditis: A Histopathologic Study on a Monocentric Series of Six Cases.

Many reports on the development of myocarditis following coronavirus disease 2019 (COVID-19) vaccination (PCVM) have emerged. However, only a few case studies have investigated endomyocardial biopsy (EMB) results. This study describes the clinicopathologic features of PCVM. We surveyed all hospitalized patients in a single university hospital in Korea and identified six cases of PCVM. All six patients underwent EMB, five of whom were men aged 15-85 years. All patients developed cardiac dysfunction. Among these patients, two had mild disease without sequelae, whereas the other four had dilated cardiomyopathy with depressed cardiac function. All six cases demonstrated lymphohistiocytic myocarditis. Two of our cases fulfilled the criterion of CD3+ T lymphocytes > 7 cells/mm2 (Case nos. 3 and 6), while the remaining four cases did not fulfill the Dallas criteria. In conclusion, most PCVM cases showed mild degree inflammation histopathologically, and some cases could not fulfill the Dallas criteria and were classified as borderline myocarditis.

TRPM7 Mediates Neuropathic Pain by Activating mTOR Signaling in Astrocytes after Spinal Cord Injury in Rats.

In this study, we investigated whether transient receptor melastatin 7 (TRPM7), known as a non-selective cation channel, inhibits neuropathic pain after spinal cord injury (SCI) and how TRPM7 regulates neuropathic pain. Neuropathic pain was developed 4 weeks after moderate contusive SCI and TRPM7 was markedly upregulated in astrocytes in the lamina I and II of L4-L5 dorsal horn. In addition, both mechanical allodynia and thermal hyperalgesia were significantly alleviated by a TRPM7 inhibitor, carvacrol. In particular, carvacrol treatment inhibited mechanistic target of rapamycin (mTOR) signaling, which was activated in astrocytes. When rats were treated with rapamycin, an inhibitor of mTOR signaling, neuropathic pain was significantly inhibited. Furthermore, blocking TRPM7 and mTOR signaling by carvacrol and rapamycin inhibited astrocyte activation in lamina I and II of dorsal spinal cord and reduced the level of p-JNK and p-c-Jun, which are known to be activated in astrocytes. Finally, inhibiting TRPM7/mTOR signaling also downregulated the production of pain-related factors such as tumor necrosis factor-α, interleukin-6, interleukin-1ß, chemokine (C-C motif) ligand (CCL) 2, CCL-3, CCL-4, CCL-20, chemokine C-X-C motif ligand 1, and matrix metalloproteinase 9 which are known to be involved in the induction and/or maintenance of neuropathic pain after SCI. These results suggest an important role of TRPM7-mediated mTOR signaling in astrocyte activation and thereby induction and/or maintenance of neuropathic pain after SCI.

TRPM7 Mediates BSCB Disruption After Spinal Cord Injury by Regulating the mTOR/JMJD3 Axis in Rats.

After spinal cord injury (SCI), secondary injuries including blood cells infiltration followed by the production of inflammatory mediators are led by blood-spinal cord barrier (BSCB) breakdown. Therefore, preventing BSCB damage could alleviate the secondary injury progresses after SCI. Recently, we reported that transient receptor potential melastatin 7 channel (TRPM7) expression is increased in vascular endothelial cells after injury and thereby mediates BSCB disruption. However, the mechanism by which TRPM7 regulates BSCB disruption has not been examined yet. In current research, we show that TRPM7 mediates BSCB disruption via mammalian target of rapamycin (mTOR) pathway after SCI in rats. After contusion injury at T9 level of spinal cord, mTOR pathway was activated in the endothelial cells of blood vessels and TRPM7 was involved in the activation of mTOR pathway. BSCB disruption, MMP-2/9 activation, and blood cell infiltration after injury were alleviated by rapamycin, a mTOR signaling inhibitor. Rapamycin also conserved the level of tight junction proteins, which were decreased after SCI. Furthermore, mTOR pathway regulated the expression and activation of histone H3K27 demethylase JMJD3, known as a key epigenetic regulator mediating BSCB damage after SCI. In addition, rapamycin inhibited JMJD3 expression, the loss of tight junction molecules, and MMP-2/9 expression in bEnd.3, a brain endothelial cell line, after oxygen-glucose deprivation/reoxygenation. Thus, our results suggest that TRPM7 contributes to the BSCB disruption by regulating JMJD3 expression through the mTOR pathway after SCI.

Two Cases of Lymph Node Metastasis Found in Differentiated, Small-Sized Gastric Adenocarcinomas: Did Tumor Budding Play a Critical Role?

Background: Endoscopic resection (ER) is a minimally invasive therapeutic approach for early gastric cancer (EGC), particularly for cases with a low risk of lymph node metastasis (LNM). Tumor budding (TB) has gained attention as a potential prognostic indicator for LNM in EGC. Case Presentation: We report two cases-a 73-year-old and an 81-year-old male patient-who presented with gastric adenocarcinoma. Both patients had small-sized, differentiated, and intramucosal adenocarcinomas. However, high-grade TBs per high-power field under ×200 magnification at the invasive front and LNMs were found in both cases. Conclusions: These cases conformed to the post-ER observation guidelines of the current treatment protocol, yet demonstrated LNMs. We found that TB could serve as an effective prognostic marker for LNM compared to traditional risk factors. The aim of this study is to re-examine the ability of TB to predict LNM in EGC, thereby providing an impetus for reconsideration and potential revision of the current treatment guidelines for EGC.

IL-6/JAK2/STAT3 axis mediates neuropathic pain by regulating astrocyte and microglia activation after spinal cord injury.

After spinal cord injury (SCI), the control of activated glial cells such as microglia and astrocytes has emerged as a promising strategy for neuropathic pain management. However, signaling mechanism involved in glial activation in the process of neuropathic pain development and maintenance after SCI is not well elucidated. In this study, we investigated the potential role and mechanism of the JAK2/STAT3 pathway associated with glial cell activation in chronic neuropathic pain development and maintenance after SCI. One month after contusive SCI, the activation of JAK2/STAT3 pathway was markedly upregulated in both microglia and astrocyte in nociceptive processing regions of the lumbar spinal cord. In addition, both mechanical allodynia and thermal hyperalgesia was significantly inhibited by a JAK2 inhibitor, AG490. In particular, AG490 treatment inhibited both microglial and astrocyte activation in the lumbar (L) 4-5 dorsal horn and significantly decreased levels of p-p38MAPK, p-ERK and p-JNK, which are known to be activated in microglia (p-p38MAPK and p-ERK) and astrocyte (p-JNK). Experiments using primary cell cultures also revealed that the JAK2/STAT3 pathway promoted microglia and astrocyte activation after lipopolysaccharide stimulation. Furthermore, JAK2/STAT3 signaling and pain behaviors were significantly attenuated when the rats were treated with anti-IL-6 antibody. Finally, minocycline, a tetracycline antibiotic, inhibited IL-6/JAK2/STAT3 signaling pathway in activated glial cells and restored nociceptive thresholds and the hyperresponsiveness of dorsal neurons. These results suggest an important role of the IL-6/JAK2/STAT3 pathway in the activation of microglia and astrocytes and in the maintenance of chronic below-level pain after SCI.

A Rare Axillary Lymph Node Metastasis on 18F-FDG PET/CT for Staging in a Patient with Common Bile Duct Cancer.

Distant metastasis of cholangiocarcinoma is most commonly diagnosed in the liver; however, it can also be found in the lungs, distant lymph nodes, bones, and brain. Distant lymph node metastasis outside the abdominal region without concurrent abdominal metastasis is exceedingly rare in extrahepatic cholangiocarcinoma. Herein, we present interesting 18F-FDG PET/CT images of a 49-year-old male patient with common bile duct cancer. In this case, the patient, who was scheduled for surgery, unexpectedly showed axillary lymph node metastasis on a preoperative 18F-FDG PET scan, which was subsequently confirmed via histological examination. Although such cases are exceptionally rare, this accurate diagnosis prompted a modification of the treatment plan, leading to a positive therapeutic response.

A Soft, High-Density Neuroelectronic Array.

Techniques to study brain activities have evolved dramatically, yet tremendous challenges remain in acquiring high-throughput electrophysiological recordings minimally invasively. Here, we develop an integrated neuroelectronic array that is filamentary, high-density and flexible. Specifically, with a design of single-transistor multiplexing and current sensing, the total 256 neuroelectrodes achieve only a 2.3 × 0.3 mm2 area, unprecedentedly on a flexible substrate. A novel single-transistor multiplexing acquisition circuit further reduces noise from the electrodes, decreased the footprint of each pixel, and potentially increased the device lifetime. The filamentary neuroelectronic array also integrates with a rollable contact pad design, allowing the device to be injected through a syringe, enabling potential minimally invasive array delivery. Successful acute auditory experiments in rats validate the ability of the array to record neural signals with high tone decoding accuracy. Together, these results establish soft, high-density neuroelectronic arrays as promising devices for neuroscience research and clinical applications.

Deep Learning-Based Computational Cytopathologic Diagnosis of Metastatic Breast Carcinoma in Pleural Fluid.

A Pleural effusion cytology is vital for treating metastatic breast cancer; however, concerns have arisen regarding the low accuracy and inter-observer variability in cytologic diagnosis. Although artificial intelligence-based image analysis has shown promise in cytopathology research, its application in diagnosing breast cancer in pleural fluid remains unexplored. To overcome these limitations, we evaluate the diagnostic accuracy of an artificial intelligence-based model using a large collection of cytopathological slides, to detect the malignant pleural effusion cytology associated with breast cancer. This study includes a total of 569 cytological slides of malignant pleural effusion of metastatic breast cancer from various institutions. We extracted 34,221 augmented image patches from whole-slide images and trained and validated a deep convolutional neural network model (DCNN) (Inception-ResNet-V2) with the images. Using this model, we classified 845 randomly selected patches, which were reviewed by three pathologists to compare their accuracy. The DCNN model outperforms the pathologists by demonstrating higher accuracy, sensitivity, and specificity compared to the pathologists (81.1% vs. 68.7%, 95.0% vs. 72.5%, and 98.6% vs. 88.9%, respectively). The pathologists reviewed the discordant cases of DCNN. After re-examination, the average accuracy, sensitivity, and specificity of the pathologists improved to 87.9, 80.2, and 95.7%, respectively. This study shows that DCNN can accurately diagnose malignant pleural effusion cytology in breast cancer and has the potential to support pathologists.

Uterine Cervical Angioleiomyoma Mimicking Squamous Cell Carcinoma.

Angioleiomyoma, a rare variant of leiomyoma, is a benign tumor of mesenchymal origin. Angioleiomyomas of the female urogenital tract are extremely rare, with only six cases of uterine cervical angioleiomyoma previously reported in the literature. In this case study, we report on a 49-year-old female patient who presented with menorrhagia whose initial magnetic resonance imaging (MRI) findings suggested cervical squamous cell carcinoma (SCC). However, following the hysterectomy, histological examination confirmed the lesion to be angioleiomyoma. To the best of our knowledge, there have been no previously reported cases of angioleiomyomas presenting with MRI findings that are suggestive of uterine SCC. Recognizing that angioleiomyomas can mimic uterine malignancies on MRI may prove beneficial for future diagnostic and treatment strategies.

Unusual Duodenal Ulcer: Metastatic Urothelial Carcinoma of the Renal Pelvis.

Metastatic urothelial carcinoma of the renal pelvis (MUCP), a type of metastatic upper tract urothelial carcinoma (MUTUC), is a rare malignancy, and some patients with MUCP present with distant metastasis at the time of diagnosis. MUCP in the gastrointestinal tract is even rarer. Herein, we report a 78-year-old man with MUCP that presented as a duodenal ulcer. He complained of anorexia, dizziness, and melena for one month. Endoscopic examination at a local clinic revealed a duodenal hemorrhagic and ulcerative lesion, and the patient was referred. He noted dark-colored stools with increasing frequency, but he denied hematochezia, coffee ground emesis, weight changes, or abdominal pain. Gastroduodenoscopic examination at our hospital demonstrated an ulcerofungating lesion of the second portion of the duodenum. Colonoscopic findings showed no abnormality. Computed tomography showed a 6.7 cm sized mass abutting the inferior vena cava, second portion of the duodenum, lower pole of the right kidney, and right iliopsoas. The mass showed heterogeneous enhancement and internal hemorrhagic necrosis and infiltrated the perinephric soft tissues, the second portion of the duodenum, the right psoas muscle, the right renal vein, and the right adrenal gland. Duodenal biopsy showed moderately differentiated squamous cell carcinoma. Immunohistochemistry (IHC) showed diffuse and strong positivity for CK5/6. Tissue from the liver biopsy showed similar histopathologic features and showed GATA3 positivity on IHC. The imprint cytology smears of the liver tissue showed "cercariform" cell features. We confirmed the diagnosis as MUCP. This case illustrated a rare cause of a secondary duodenal tumor, MUCP.

GSK-3ß and ß-Catenin Signaling Pathway is Involved in Myofibroblast Transition of Ligamentum Flavum in Lumbar Spinal Stenosis Patients.

STUDY DESIGN: Histologic analysis of the ligamentum flavum (LF) in the lumbar spine. OBJECTIVE: The objective of this study is to investigate the levels of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin in the LF tissue of patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: The hypertrophy of the LF is the primary cause of the progression of LSS. Recently, Wnt signaling has been proposed as one of the molecular processes contributing to LF hypertrophy. GSK-3ß and ß-catenin are recognized to play a crucial part in the control of this signaling pathway. MATERIALS AND METHODS: From May 2020 to July 2022, LF from 51 LSS patients (LSS group) and 18 lumbar disc herniation patients (control group) were prospectively collected during surgery. Histologic analysis was investigated to confirm the progression of LF fibrosis. The levels of α-smooth muscle actin, phosphorylation of GSK-3ß (p-GSK-3ß; inactive form), and ß-catenin were analyzed in LF with Western blot analysis to reveal the GSK-3ß/ß-catenin signaling pathway. Continuous variables are expressed as mean±SD and compared using the student t test. Categorical variables are compared using the χ 2 test or Fisher exact test, as appropriate. To determine the association between p-GSK-3ß and LF thickness, the Pearson correlation coefficient was calculated based on the results of Western blot analysis. RESULTS: The LSS group was older and had thicker LF than the controls. The LSS group showed increased collagen fiber and cellularity than the controls. The levels of α-smooth muscle actin, p-GSK-3ß, and ß-catenin in the LF of the LSS group were significantly higher than that of the control group. There was a strong positive correlation between p-GSK-3ß (Ser9) level and LF thickness in LSS patients ( r =0.69, P =0.01). CONCLUSION: This research proposes a molecular mechanism for the pathogenesis of LF hypertrophy in LSS. Specifically, GSK-3ß/ß-catenin signaling appears to be related to LF hypertrophy in LSS and a positive correlation exists between p-GSK-3ß level and LF thickness. LEVEL OF EVIDENCE: Level 3.

AGE-RAGE axis culminates into multiple pathogenic processes: a central road to neurodegeneration.

Advanced glycation end-products (AGEs; e.g., glyoxal, methylglyoxal or carboxymethyl-lysine) are heterogenous group of toxic compounds synthesized in the body through both exogenous and endogenous pathways. AGEs are known to covalently modify proteins bringing about loss of functional alteration in the proteins. AGEs also interact with their receptor, receptor for AGE (RAGE) and such interactions influence different biological processes including oxidative stress and apoptosis. Previously, AGE-RAGE axis has long been considered to be the maligning factor for various human diseases including, diabetes, obesity, cardiovascular, aging, etc. Recent developments have revealed the involvement of AGE-RAGE axis in different pathological consequences associated with the onset of neurodegeneration including, disruption of blood brain barrier, neuroinflammation, remodeling of extracellular matrix, dysregulation of polyol pathway and antioxidant enzymes, etc. In the present article, we attempted to describe a new avenue that AGE-RAGE axis culminates to different pathological consequences in brain and therefore, is a central instigating component to several neurodegenerative diseases (NGDs). We also invoke that specific inhibitors of TIR domains of TLR or RAGE receptors are crucial molecules for the therapeutic intervention of NGDs. Clinical perspectives have also been appropriately discussed.

Epigenomic landscape exhibits interferon signaling suppression in the patient of myocarditis after BNT162b2 vaccination.

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-α/γ in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination.