New-onset Fibromyalgia After Total Knee Replacement in Patients With Osteoarthritis: A Propensity-score-matched Cohort Study in the United States.

BACKGROUND/AIM: The risk of new-onset fibromyalgia after total knee replacement (TKR) in osteoarthritis patients is not well-established. This study aimed to assess the risk of developing fibromyalgia post-TKR, considering potential variations across age and sex. PATIENTS AND METHODS: Utilizing a multicenter retrospective cohort design and data from the TriNetX research network, electronic health records of osteoarthritis patients who underwent TKR and the same number of matched controls were analyzed. Propensity-score matching was performed by matching critical confounders. Hazard ratios were evaluated to assess fibromyalgia risk in the TKR cohort compared to non-TKR controls. RESULTS: The hazard ratio of future fibromyalgia for the TKR cohort was 2.08 (95% confidence interval=1.74-2.49) for 1 year after the index date, 1.81 (95% confidence interval=1.62-2.02) for 3 years, and 1.69 (95% confidence interval=1.54-1.86) for 5 years compared with non-TKR controls. The significant association remained in sensitivity models and stratification analyses in different age and sex subgroups. CONCLUSION: Clinicians should be vigilant about the potential for fibromyalgia development post-TKR and consider tailored interventions; our findings emphasize the need for further research to elucidate underlying mechanisms and identify modifiable risk factors.

Targeting chondroitin sulfate suppresses macropinocytosis of breast cancer cells by modulating syndecan-1 expression.

Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF-associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6-O-sulfated CS-binding peptide (C6S-p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF-ß) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS-SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient-deprived conditions. Furthermore, C6S-p demonstrated the ability to bind CS-SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF-regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells.

Research trends in alopecia areata: a cross-sectional bibliometric analysis of the top cited studies.

In the field of alopecia areata research, various focuses including risk factors, epidemiology, molecular pathways, and treatment were constantly improving. However, to date, a bibliometric analysis summarizing the research trend is not available to date. The main objective of this study was to provide researchers with an overview of the research trend on alopecia areata in the past two decades. In Web of Science database, screening and extraction of studies related to alopecia areata has been performed. Within studies related to alopecia areata, the most cited 100 studies were appraised and the information of articles, including the citation amounts, keywords and publication types, was extracted for analyses. On average, each study in the top 100 list was cited 104.72 times. Within the top 100 list, the most focused fields were on the management of alopecia areata (34%), molecular mechanisms (28%) and epidemiological issues (23%). Approximately one third of the management-associated studies focused on Janus kinase (JAK) inhibitors (10 studies) and 5 studies focused on the efficacy of corticosteroids for alopecia areata. According to the results of the keyword analysis, JAK inhibitors had become the most mentioned keywords in the field of alopecia areata research since 2016. The top 100 most referenced papers in the field of alopecia areata mostly focused on essential aspects such as treatment options, pathogenesis, risk factors, and comorbidities. The results of the current study could be considered a potential resource for future research and patient care information.

Roles of Neuronal Protein Kinase Cε on Endoplasmic Reticulum Stress and Autophagic Formation in Diabetic Neuropathy.

In chronic diabetic neuropathy (DN), the cellular mechanisms of neuropathic pain remain unclear. Protein kinase C epsilon (PKCε) is an intracellular signaling molecule that mediates chronic pain. This paper addresses the long-term upregulated PKCε in DN associated with endoplasmic reticulum (ER) stress and autophagic formation and correlates to chronic neuropathic pain. We found that thermal hyperalgesia and mechanical allodynia course development were associated with PKCε upregulation after DN but not skin denervation. Pathologically, PKCε upregulation was associated with the expression of inositol-requiring enzyme 1α (IRE1α; ER stress-related molecule) and ubiquitin D (UBD), which are involved in the ubiquitin-proteasome system (UPS)-mediated degradation of misfolded proteins under ER stress. Manders coefficient analyses revealed an approximately 50% colocalized ratio for IRE1α(+):PKCε(+) neurons (0.34-0.48 for M1 and 0.40-0.58 for M2 Manders coefficients). The colocalized coefficients of UBD/PKCε increased (M1: 0.33 ± 0.03 vs. 0.77 ± 0.04, p < 0.001; M2: 0.29 ± 0.05 vs. 0.78 ± 0.04; p < 0.001) in the acute DN stage. In addition, the regulatory subunit p85 of phosphoinositide 3-kinase, which is involved in regulating insulin signaling, exhibited similar expression patterns to those of IRE1α and UBD; for example, it had highly colocalized ratios to PKCε. The ultrastructural examination further confirmed that autophagic formation was associated with PKCε upregulation. Furthermore, PKCεv1-2, a PKCε specific inhibitor, reverses neuropathic pain, ER stress, and autophagic formation in DN. This finding suggests PKCε plays an upstream molecule in DN-associated neuropathic pain and neuropathology and could provide a potential therapeutic target.

CHST11-modified chondroitin 4-sulfate as a potential therapeutic target for glioblastoma.

Aberrant chondroitin sulfate (CS) accumulation in glioblastoma (GBM) tissue has been documented, but the role of excessive CS in GBM progression and whether it can be a druggable target are largely unknown. The aim of this study is to clarify the biological functions of CHST11 in GBM cells, and evaluate therapeutic effects of blocking CHST11-derived chondroitin 4-sulfate (C4S). We investigated the expression of CHST11 in glioma tissue by immunohistochemistry, and analyzed CHST11 associated genes using public RNA sequencing datasets. The effects of CHST11 on aggressive cell behaviors have been studied in vitro and in vivo. We demonstrated that CHST11 is frequently overexpressed in GBM tissue, promoting GBM cell mobility and modulating C4S on GBM cells. We further discovered that CSPG4 is positively correlated with CHST11, and CSPG4 involved in CHST11-mediated cell invasiveness. In addition, GBM patients with high expression of CHST11 and CSPG4 have a significantly shorter survival time. We examined the effects of treating C4S-specific binding peptide (C4Sp) as a therapeutic agent in vitro and in vivo. C4Sp treatment attenuated GBM cell invasiveness and, notably, improved survival rate of orthotopic glioma cell transplant mice. Our results propose a possible mechanism of CHST11 in regulating GBM malignancy and highlight a novel strategy for targeting aberrant chondroitin sulfate in GBM cells.

Small intestine submucosa as a growth factor attractor promotes peripheral nerve regeneration by enhancing syndecan-3/glial cell line-derived neurotrophic factor (GDNF) signalling:in vivostudy.

Peripheral nerve regeneration (PNR) following trauma requires the reconstruction of the extracellular matrix (ECM) and the proper stimulation of growth factors. Decellularised small intestine submucosa (SIS) has been extensively used as an ECM scaffold for tissue repair, but its potential to enhance the effects of exogenous growth factors on PNR is not well understood. In this study, we evaluated the effects of SIS implantation combined with glial cell-derived growth factor (GDNF) treatment on PNR in a rat neurorrhaphy model. We found that both SIS and regenerating nerve tissue expressed syndecan-3 (SDC3), one of major heparan sulphate proteoglycans in nerve tissue, and that SDC3 interacted with GDNF in the regenerating nerve tissue. Importantly, the SIS-GDNF combined treatment enhanced the recovery of neuromuscular function andß3-tubulin-positive axonal outgrowth, indicating an increase in the number of functioning motor axons connecting to the muscle after neurorrhaphy. Our findings suggest that the SIS membrane offers a new microenvironment for neural tissue and promotes neural regeneration based on SDC3-GDNF signalling, providing a potential therapeutic approach for PNR.

Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation.

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.

Survival analysis of malignant peripheral nerve sheath tumor: Experience of a tertiary center in Taiwan.

BACKGROUND: This study aimed to analyze the demographic characteristics and prognostic factors of malignant peripheral nerve sheath tumor (MPNST) in a Taiwanese population. Single-center treatment outcomes were also presented. METHODS: This retrospective cohort study analyzed the medical records of 54 patients with pathological diagnoses of MPNSTs from 2005 to 2021 at a single institution. The primary endpoint was the 5-year overall survival rate of MPNST, and the secondary endpoint was recurrence-free 5-year survival. Variables including patient characteristics, metastasis status at initial diagnosis, and surgical outcomes were analyzed with competing risk analysis. RESULTS: Among all 41 eligible patients diagnosed with MPNST, female predominance was noted, and the median age at diagnosis was 44 years. The most common site of lesion was found at the trunk (46.34%), and eight patients were diagnosed with notable metastasis. Twelve patients were diagnosed with type 1 neurofibromatosis (NF1). The 5-year overall survival rate was 36.84% and the 5-year recurrence-free survival was 28.95%. Metastasis diagnosed at presentation, large lesion sizes, and recurrence were identified as significant poor prognostic factors of survival. Metastasis diagnosed at presentation was identified as the only significant risk factor of recurrence. CONCLUSION: In our series, metastasis diagnosed at presentation, large lesion sizes, and recurrence were identified as significant poor prognostic factors of survival. Metastasis was also identified as the only significant risk factor of recurrence. NF1-associated MPNSTs presented with significantly larger tumor sizes and additional treatment postoperatively did not significantly improve survival. The limitations of this study include its retrospective nature and sample size.

Effects of the individual three-dimensional printed craniofacial bones with a quick response code on the skull spatial knowledge of undergraduate medical students.

Understanding the three-dimensional (3D) structure of the human skull is imperative for medical courses. However, medical students are overwhelmed by the spatial complexity of the skull. Separated polyvinyl chloride (PVC) bone models have advantages as learning tools, but they are fragile and expensive. This study aimed to reconstruct 3D-printed skull bone models (3D-PSBs) using polylactic acid (PLA) with anatomical characteristics for spatial recognition of the skull. Student responses to 3D-PSB application were investigated through a questionnaire and tests to understand the requirement of these models as a learning tool. The students were randomly divided into 3D-PSB (n = 63) and skull (n = 67) groups to analyze pre- and post-test scores. Their knowledge was improved, with the gain scores of the 3D-PSB group (50.0 ± 3.0) higher than that of the skull group (37.3 ± 5.2). Most students agreed that using 3D-PSBs with quick response codes could improve immediate feedback on teaching (88%; 4.41 ± 0.75), while 85.9% of the students agreed that individual 3D-PSBs clarified the structures hidden within the skull (4.41 ± 0.75). The ball drop test revealed that the mechanical strength of the cement/PLA model was significantly greater than that of the cement or PLA model. The prices of the PVC, cement, and cement/PLA models were 234, 1.9, and 10 times higher than that of the 3D-PSB model, respectively. These findings imply that low-cost 3D-PSB models could revolutionize skull anatomical education by incorporating digital technologies like the QR system into the anatomical teaching repertoire.

Risk of osteoarthritis in patients with hidradenitis suppurativa: a global federated health network analysis.

Background: Osteoarthritis and hidradenitis suppurativa (HS) share a common inflammatory pathway. However, whether patients with HS have higher risk developing osteoarthritis remained unclear. Methods: A retrospective cohort design was adopted in this study. Electronic medical records had been retrieved from the US collaborative network in the TriNetX research network. A propensity score matching of 1:1 was performed to match for covariates. In total, 50,931 patients with HS and the same amount of non-HS controls were identified for analyses. Hazard ratio (HR) of osteoarthritis in patient with HS was calculated. Results: Risk of patients with HS developing osteoarthritis was 1.37-fold higher than that of non-HS controls [95% confidence interval (CI), 1.21-1.55] when followed up for 1 year. The significance remained when the follow-up periods were extended to 3 years and 5 years. When osteoarthritis was stratified on occurring sites, the HR of knee osteoarthritis was 1.19 (95% CI, 1.09-1.29) and the HR of hip osteoarthritis was 1.17 (95% CI, 1.01-1.35) in the 5-year follow-up. The 5-year risk of osteoarthritis remained significant in sensitivity models. Conclusion: Patients with HS were of high risk of developing osteoarthritis compared with people without HS. The clinical association was recommended to be considered while approaching patients with HS.

Olfactory Stimulation Successfully Modulates the Neurochemical, Biochemical and Behavioral Phenotypes of the Visceral Pain.

Visceral pain (VP) is the organ-derived nociception in which increased inflammatory reaction and exaggerated activation of the central nucleus of the amygdala (CeA) may contribute to this deficiency. Considering the amygdala also serves as the integration center for olfaction, the present study aimed to determine whether olfactory stimulation (OS) would effectively depress over-activation and inflammatory reaction in CeA, and successfully relieve VP-induced abnormalities. Adult rats subjected to intraperitoneal injection of acetic acid inhaled lavender essential oil for 2 or 4 h. The potential benefits of OS were determined by measuring the pro-inflammatory cytokine level, intracellular potassium and the upstream small-conductance calcium-activated potassium (SK) channel expression, together with detecting the stress transmitters that participated in the modulation of CeA activity. Results indicated that in VP rats, strong potassium intensity, reduced SK channel protein level, and increased corticotropin-releasing factor, c-fos, and substance P immuno-reactivities were detected in CeA. Enhanced CeA activation corresponded well with increased inflammatory reaction and decreased locomotion, respectively. However, in rats subjected to VP and received OS, all above parameters were significantly returned to normal levels with higher change detected in treating OS of 4h. As OS successfully depresses inflammation and CeA over-activation, application of OS may serve as an alternative and effective strategy to efficiently relieve VP-induced deficiency.

Arcade Suture Upper Blepharoplasty Combined With the Forceps Technique.

BACKGROUND: Double-eyelid blepharoplasty is the most popular cosmetic surgery in Taiwan. The creation of a small palpebral fold along with reduction of eyelid fullness makes the eye look slightly larger, thereby leading to an appearance of youthfulness, alertness, and vitality. Herein, we propose a method of combining the techniques of arcade buried suture and forceps, which is designed to create a more physiologically natural double eyelid. MATERIALS AND METHODS: We conducted a retrospective review of 45 patients who underwent double-eyelid surgery between December 2015 and December 2019. The procedures were performed by one senior surgeon using arcade suture upper blepharoplasty combined with the forceps technique. The patients' age ranged from 18 to 38 years (mean, 28 years). Ninety-one percent of the patients were women and were undergoing surgery for cosmetic reasons. RESULTS: Of the 45 patients who underwent arcade suture upper blepharoplasty with the forceps technique, no patients developed stitch abscess or granuloma, obvious asymmetry, disappearance of line, chemosis, and corneal injury. The follow-up period ranged from 3 months to 4 years (mean, 32 months). Patient satisfaction was very high. CONCLUSIONS: The arcade suture upper blepharoplasty combined with the forceps technique is a simple method for establishing a durable double eyelid without serious complication and providing excellent results.

Postoperative Sedation Duration as an Independent Risk Factor for Postoperative Pneumonia in Head and Neck Cancer Patients Undergoing Free Flap Reconstruction.

OBJECTIVE: Patients who had reconstruction for head and neck cancer usually have long duration of postoperative sedation and intensive care. This is due to the complex nature of large-area soft tissue defect surgeries and upper respiratory tract infections associated with them. Postoperative pulmonary complications are common in these patients. In this study, we analyzed the risk factors and the relationship between postoperative complications and the duration of sedation to improve the patients' recovery process after free flap reconstruction for head and neck surgery. MATERIALS AND METHODS: This was a retrospective study that included 188 patients who had head and neck surgery with free flap reconstruction in 2011 (traditional recovery group) and 2018 (early recovery group). Postoperative recovery events were compared between the 2 groups. Complications such as pneumonia, wound infection, vascular thrombosis, and bleeding were also analyzed. RESULTS: The results showed that the early recovery group had a shorter duration of sedation (P < 0.001), shorter duration of intensive care unit stay (P = 0.05), more rapid ventilator weaning (P < 0.001), and fewer pneumonia events (8.8% vs 39.1%) than the traditional recovery group. Wound- and vessel-related complications were not affected by the duration of sedation. CONCLUSIONS: Our study demonstrated that shortening the duration of postoperative sedation can effectively decrease the length of intensive care unit stay and reduce postoperative incidence of pneumonia without increasing wound- and vessel-related complications.

Olfactory Stimulation Successfully Improves Swallowing Function of Aged Rats Through Activating Central Neuronal Networks and Downstream DHPR-RyR-mediated Neuromuscular Activities.

Presbyphagia is age-related changes in swallowing function, which imposes a high risk of aspiration in older adults. Considering olfactory stimulation (OS) can influence behavioral activities by modulating neuronal excitability, the present study aims to determine whether OS could improve the swallowing function of aged rats through activating the central neuronal networks and downstream muscular activities participated in the control of swallowing. Aged male Wistar rats received OS by inhaling a mixture of plant-based volatile molecules twice a day for 12 days were subjected to functional magnetic resonance imaging (fMRI) and c-fos, choline acetyltransferase (ChAT) immunostaining to detect the neuronal activities of the orbitofrontal cortex (OFC) and medullary nuclei engaged in swallowing control, respectively. The functional effects of OS on downstream pharyngeal muscle activity were examined by evaluating the dihydropyridine receptor-ryanodine receptor (DHPR-RyR)-mediated intramuscular Ca2+ expression, and analyzing the amplitude/frequency of muscle contraction, respectively. In untreated rats, only moderate signal of fMRI and mild c-fos/ChAT expression was detected in the OFC and medullary nuclei, respectively. However, following OS, intense signals of fMRI and immunostaining were clearly expressed in the orbitofronto-medullary networks. Functional data corresponded well with above findings in which OS significantly enhanced DHPR-RyR-mediated intramuscular Ca2+ expression, effectively facilitated a larger amplitude of pharyngeal muscle contraction, and exhibited better performance in consuming larger amounts of daily dietary. As OS successfully activates the neuromuscular activities participated in the control of swallowing, applying OS may serve as an effective, easy, and safe strategy to greatly improve the swallow function of aging populations.

Risk of liver dysfunction and non-alcoholic fatty liver diseases in people with hidradenitis suppurativa: A systematic review and meta-analysis of real-world evidences.

Background: To date, evidences with high evidence-level evaluating the association between liver diseases and hidradenitis suppurativa was lacking. Given that inconsistency exists in some of the previous observational studies, evaluating the prevalence of liver diseases in HS patients could potentially serve as a reference of future guidelines for HS comorbidity screening. The aim of the current study was to evaluate potential association between hidradenitis suppurativa and liver diseases and provide integrated evidences. Methods: A search in PubMed, Web of Science and Embase based on the syntaxes ''hidradenitis suppurativa'' or ''acne inversa'' with "comorbidities", "liver diseases", "fatty liver" or "hepatitis" was performed. Observational studies evaluating epidemiological association between hidradenitis suppurativa and the risk of all liver diseases, including specific diseases as non-alcoholic fatty liver disease, hepatitis B, hepatitis C were targeted to be extracted in this systematic review and meta-analysis. Results: Within the initial 702 records, there were finally 8 real-world observational studies extracted. Results suggest that patients with HS are associated with all liver diseases (OR= 1.50; 95% CI, 1.27, 1.76), non-alcoholic fatty liver disease (OR= 1.78; 95% CI, 1.28, 2.48) and hepatitis B (OR=1.48; 95% CI, 1.12, 1.94), but not hepatitis C (OR= 1.27; 95% CI, 0.78, 2.07). HS patients were associated with significantly increased risk of liver diseases, especially the risk of non-alcoholic fatty liver disease and hepatitis B. Conclusions: Clinicians should be alert to the clinical relationship while caring people with hidradenitis suppurativa and the screening of liver function should be recommended to HS patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022296034.

Fucosyltransferase 8 modulates receptor tyrosine kinase activation and temozolomide resistance in glioblastoma cells.

Alteration of extracellular glycosylation is a hallmark of malignant characteristics. In this study, we revealed that fucosyltransferase 8 (FUT8), an enzyme that mediates the core fucosylation of N-linked glycosylation, is an important regulator of malignant characteristics in human glioma that acts by modifying the activities of both the HGF receptor (MET) and epidermal growth factor receptor (EGFR). mRNA and protein expression levels of FUT8 were frequently upregulated in gliomas, and these events were showed positive correlations with advanced tumor grade, recurrence, and decreased overall survival. Silencing FUT8 expression in glioma cells suppressed cell growth, migration, and invasion, whereas overexpression of FUT8 was sufficient to enhance these phenotypes. Mechanistic investigations revealed that FUT8 was involved in the alteration of fucosylation status that was attached to MET and EGFR, changing MET responses after HGF stimulation, as well as in the transactivation of EGFR. Importantly, altering FUT8 expression or using the fucosylation inhibitor 2F-peracetyl-fucose sensitized the efficacy of of temozolomide (TMZ) therapy. Collectively, these results suggested that FUT8 dysregulation contributed to the malignant behaviors of glioma cells and provide novel insights into the significance of fucosylation in receptor tyrosine kinase activity and TMZ resistance.

Targeting Chondroitin Sulfate Reduces Invasiveness of Glioma Cells by Suppressing CD44 and Integrin ß1 Expression.

Chondroitin sulfate (CS) is a major component of the extracellular matrix found to be abnormally accumulated in several types of cancer tissues. Previous studies have indicated that CS synthases and modification enzymes are frequently elevated in human gliomas and are associated with poor prognosis. However, the underlying mechanisms of CS in cancer progression and approaches for interrupting its functions in cancer cells remain largely unexplored. Here, we have found that CS was significantly enriched surrounding the vasculature in a subset of glioma tissues, which was akin to the perivascular niche for cancer-initiating cells. Silencing or overexpression of the major CS synthase, chondroitin sulfate synthase 1 (CHSY1), significantly regulated the glioma cell invasive phenotypes and modulated integrin expression. Furthermore, we identified CD44 as a crucial chondroitin sulfate proteoglycan (CSPG) that was modified by CHSY1 on glioma cells, and the suppression of CS formation on CD44 by silencing the CHSY1-inhibited interaction between CD44 and integrin ß1 on the adhesion complex. Moreover, we tested the CS-specific binding peptide, resulting in the suppression of glioma cell mobility in a fashion similar to that observed upon the silencing of CHSY1. In addition, the peptide demonstrated significant affinity to CD44, promoted CD44 degradation, and suppressed integrin ß1 expression in glioma cells. Overall, this study proposes a potential regulatory loop between CS, CD44, and integrin ß1 in glioma cells, and highlights the importance of CS in CD44 stability. Furthermore, the targeting of CS by specific binding peptides has potential as a novel therapeutic strategy for glioma.

Treatment with the combination of clavulanic acid and valproic acid led to recovery of neuronal and behavioral deficits in an epilepsy rat model.

Epilepsy, which is caused by abnormal neuronal firing in the brain, is a common neurological disease and affects motor and cognitive functions. Excessive levels of glutamate and insufficient levels of inhibitory GABA are involved in its pathophysiology. Valproic acid (Val), a GABAergic agonist, is one of the first-line antiepileptic drugs, but it shows many adverse side effects at the clinical dose. Clavulanic acid (CA), a ß-lactamase inhibitor, has been demonstrated to increase glutamate transporter-1 expression. This study evaluated the effects of CA and Val in an epilepsy rat model. Male Wistar rats received intraperitoneal injections of pentylenetetrazol (PTZ, 35 mg/kg, every other day, IP, for 13 days) to induce kindling epilepsy. After four times of PTZ injection, rats received daily treatment with CA (1 or 10 mg/kg, IP), Val (50 or 100 mg/kg, IP), or the combination of CA (1 mg/kg) and Val (50 mg/kg) for 7 consecutive days. Motor, learning, and memory functions were measured. Rats with PTZ-induced kindling exhibited seizures, motor dysfunction, cognitive impairment, and cell loss and reduction of neurogenesis in the hippocampus. Neither 1 mg/kg CA nor 50 mg/kg Val treatment was effective in alleviating behavioral and neuronal deficits. However, treatment with 10 mg/kg CA, 100 mg/kg Val, and the combination of 1 mg/kg CA and 50 mg/kg Val improved these behavioral and neuronal deficits. Particularly, the combination of CA and Val showed synergistic effects on seizure suppression, suggesting the potential for treating epilepsy and related neuronal damage and motor and cognitive deficits.

Quercetin Alleviates the Accumulation of Superoxide in Sodium Iodate-Induced Retinal Autophagy by Regulating Mitochondrial Reactive Oxygen Species Homeostasis through Enhanced Deacetyl-SOD2 via the Nrf2-PGC-1α-Sirt1 Pathway.

Oxidative damage of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Quercetin, a bioactive flavonoid compound, has been shown to have a protective effect against oxidative stress-induced cell apoptosis and inflammation in RPE cells; however, the detailed mechanism underlying this protective effect is unclear. Therefore, the aim of this study was to investigate the regulatory mechanism of quercetin in a sodium iodate (NaIO3)-induced retinal damage. The clinical features of the mice, the production of oxidative stress, and the activity of autophagy and mitochondrial biogenesis were examined. In the mouse model, NaIO3 treatment caused changes in the retinal structure and reduced pupil constriction, and quercetin treatment reversed the oxidative stress-related pathology by decreasing the level of superoxide dismutase 2 (SOD2) while enhancing the serum levels of catalase and glutathione. The increased level of reactive oxygen species in the NaIO3-treated ARPE19 cells was improved by treatment with quercetin, accompanied by a reduction in autophagy and mitochondrial biogenesis. Our findings indicated that the effects of quercetin on regulating the generation of mtROS were dependent on increased levels of deacetyl-SOD2 through the Nrf2-PGC-1α-Sirt1 signaling pathway. These results demonstrated that quercetin may have potential therapeutic efficacy for the treatment of AMD through the regulation of mtROS homeostasis.