Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma.

L1 cell adhesion molecule (L1CAM) has been implicated in the progression and metastasis of numerous cancers. However, the role of L1CAM in oral squamous cell carcinoma (OSCC) is not well characterized. In the present study, the expression of L1CAM was examined in oral tongue squamous cell carcinoma (OTSCC) tissue samples by immunohistochemistry, the clinicopathological significance of L1CAM expression was evaluated by chi­squared test, and the overall survival (OS) rate was analyzed using Kaplan­Meier method according to the expression of L1CAM. In addition, it was aimed to elucidate the biological role of L1CAM and the underlying molecular mechanisms by which L1CAM functions in OSCC cells in relation to epithelial­mesenchymal transition (EMT) and PI3K/AKT/ERK signaling pathways. Thus, the functions of L1CAM on the OSCC cell proliferation, migration and invasion, and the activation of EMT and PI3K/AKT/ERK signaling pathways were investigated in vitro. Positive L1CAM expression was found in 32.5% of OTSCC cases and was significantly correlated with high histologic grade, greater depth of invasion, lymph node metastasis, perineural invasion, advanced stage, and survival status. Patients with positive L1CAM expression had significantly lower OS rate. Particularly in patients with early OTSCC, L1CAM expression was strongly associated with worse prognosis. Overexpression of the recombinant human L1CAM protein significantly increased cell proliferation, migration and invasion. By contrast, L1CAM knockdown using small interfering RNA significantly inhibited cell proliferation, migration, invasion and EMT. Moreover, phosphorylated (p)­PI3K, p­AKT and p­ERK expression levels were significantly reduced by L1CAM knockdown. Taken together, the findings of the present study suggested that L1CAM could be a potential prognostic marker and a promising therapeutic target in OSCC.

Analysis of Vaccenic and Elaidic acid in foods using a silver ion cartridge applied to GC × GC-TOFMS.

Background: Trans fatty acids (TFAs) are unsaturated fatty acids, with vaccenic acid (VA) and elaidic acid (EA) being the major constituents. While VA has been associated with beneficial effects on health and anti-cancer properties, EA is found in hardened vegetable oils and is linked to an increased risk of cardiovascular diseases. Therefore, this study aimed to develop a novel method for the quantitative measurement of VA and EA, aiming to accurately analyze individual TFA and apply it for the assessment of products containing TFAs. Methods: The ratio of VA to EA (V/E ratio) was evaluated using a silver ion cartridge (SIC) solid phase extraction method removing cis-fatty acids (cis-FAs). Additionally, comparative analysis of the V/E ratio was conducted by the two methods (SIC treatment and untreated) using comprehensive two-dimensional gas chromatography combined with time-of-flight mass spectrometry (GC × GC-TOFMS). Results: The removal efficiency of cis-FAs was greater than 97.8%. However, the total TFA contents were not so different from SIC treatment. Moreover, this approach not only allowed for a more precise determination of the V/E ratio but also revealed a significant distinction between natural trans fatty acids (N-TFAs) and hydrogenated trans fatty acids (H-TFAs). Conclusion: Therefore, the SIC coupled to the GC × GC-TOFMS presented in this study could be applied to discriminate N-TFA and H-TFA contents in dairy and fatty foods.

Risk assessment of polycyclic aromatic hydrocarbons in meat and edible oils: results of a total diet study in South Korea.

Polycyclic aromatic hydrocarbons (PAHs) constitute carcinogens. In this study, the risk of PAHs being consumed through meat and edible oils was assessed using a total diet study. Results were monitored by applying the toxic equivalency factor of benzo[a]pyrene; among each category, this factor was highest in grilled beef chitterlings (1.35 µg/kg), grilled Wiener sausages (1.20 µg/kg), fried chicken wings (0.70 µg/kg), and stir-fried perilla oil (1.29 µg/kg). The chronic daily intake was calculated, and risk characterization was estimated by applying the margin of exposure using the benchmark dose approach. Most samples analyzed in our study were denoted as having no concern; however, the intake group of stir-fried beef chitterlings, pan-fried pink sausage, deep-fried pork loin, and grilled duck was regarded as possible concern, and grilled chicken was assessed as having low concern. PAH changes must be monitored on a regular basis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01137-5.

High Molecular Weight Fucoidan Restores Intestinal Integrity by Regulating Inflammation and Tight Junction Loss Induced by Methylglyoxal-Derived Hydroimidazolone-1.

Fucoidan from brown seaweeds has several biological effects, including preserving intestinal integrity. To investigate the intestinal protective properties of high molecular weight fucoidan (HMWF) from Undaria pinnatifida on intestinal integrity dysfunction caused by methylglyoxal-derived hydroimidazolone-1 (MG-H1), one of the dietary advanced-glycation end products (dAGEs) in the human-colon carcinoma-cell line (Caco-2) cells and ICR mice. According to research, dAGEs may damage the intestinal barrier by increasing gut permeability. The findings of the study showed that HMWF + MG-H1 treatment reduced by 16.8% the amount of reactive oxygen species generated by MG-H1 treatment alone. Furthermore, HMWF + MGH-1 treatment reduced MG-H1-induced monolayer integrity disruption, as measured by alterations in transepithelial electrical resistance (135% vs. 75.5%) and fluorescein isothiocyanate incorporation (1.40 × 10-6 cm/s vs. 3.80 cm/s). HMWF treatment prevented the MG-H1-induced expression of tight junction markers, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells and mouse colon tissues at the mRNA and protein level. Also, in Caco-2 and MG-H1-treated mice, HMWF plays an important role in preventing receptor for AGEs (RAGE)-mediated intestinal damage. In addition, HMWF inhibited the nuclear factor kappa B activation and its target genes leading to intestinal inflammation. These findings suggest that HMWF with price competitiveness could play an important role in preventing AGEs-induced intestinal barrier dysfunction.

Combined effects of cadmium and ochratoxin A on intestinal barrier dysfunction in human Caco-2 cells and pig small intestinal epithelial cells.

Hazardous chemicals are commonly found in cereals and cereal-based products. However, most studies focus on the individual effects of these mycotoxins or metals, rather than their combined toxicity. The main objective of this study was to evaluate the combined effects of cadmium (Cd) and ochratoxin A (OTA) on intestinal barrier integrity using Caco-2 cells and pig small intestinal epithelial (PSI) cells as models of intestinal epithelial cells and to measure alterations in cell survival and barrier integrity. The combined effects on cell viability were assessed in terms of a combination of index values. These findings showed that co-exposure to Cd + OTA had synergistic effects on Caco-2 and PSI cells at 25%, 50%, and 75% inhibitory concentrations (IC25, IC50, and IC75, respectively) against cell viability. Individual Cd and OTA treatments had no effect, but combined Cd + OTA exposure resulted in synergistic down-regulation of paracellular apical junction complex proteins, such as claudin-1, occludin, and E-cadherin. The current findings indicate that the combined effects of OTA + Cd may have consequences at the gut level, which should not be underestimated when considering their risk to human health.

Which lateralization designed prosthesis of reverse total shoulder arthroplasty (glenoid-based lateralization vs humerus-based lateralization) would be better? Network Meta-analysis.

PURPOSE: To demonstrate the differences between outcomes and complications after reverse total shoulder arthroplasty (rTSA), according to the types of lateralized prosthesis designs: glenoid-based lateralization (LG) and humerus-based lateralization (LH). METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched for studies published before 1 April 2021, using the PRISMA guidelines. A network meta-analysis was applied for indirect comparison, incorporating studies including medialized or conventional Grammont prosthesis and each lateralized prosthesis (LG vs control and LH vs control). Out of 1,989 screened studies, 11 studies were included to compare functional scores, range of motion (ROM), radiologic outcomes, and revision rates. In addition, six articles from the included studies, which had repaired subscapularis after rTSA were analyzed to exclude the potential influence of subscapularis repair on the outcomes. The data were pooled using a random-effects model. The pooled estimates of the mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous data, while dichotomous data were analyzed using the pooled relative risk (RR) and their 95% CIs. RESULTS: The ROM, complications, and functional scores were similar between the two groups. In subgroup analysis of 6 studies involving concomitant subscapularis repair, the LH group showed higher American Shoulder and Elbow Surgeons (ASES) scores and Constant scores than the control group. Regarding the ROM, LH group showed better forward elevation than the LG group (LH vs LG: MD 10.07, 95% CI -9.05-29.19). CONCLUSION: Overall, the outcomes and occurrence of complications were not significantly different between the two lateralized prosthesis groups. However, when the subscapularis was repaired, LH prosthesis seems to be more suitable to obtain a better ASES score and ROM. LEVEL OF EVIDENCE: Level III, network meta-analysis.

Homeostasis effects of fermented Maillard reaction products by Lactobacillus gasseri 4M13 in dextran sulfate sodium-induced colitis mice.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) continues to increase worldwide. Multiple factors, including diet, loss of the intestinal barrier function, and imbalance of the immune system can cause IBD. A balanced diet is important for maintaining a healthy bowel and preventing IBD from occurring. The effects of probiotic Lactobacillus gasseri-fermented Maillard reaction products (MRPs) prepared by reacting whey protein with galactose on anti-inflammation and intestinal homeostasis were investigated in this study, which compared MPRs and probiotics separately. RESULTS: In an animal colitis model induced by 2% dextran sulfate sodium (DSS), FWG administration alleviated colon length loss and maintained intestinal immune system homeostasis as reflected by down-regulated interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α output, and metallopeptidase-9, and epithelial barrier balance as reflected by up-regulated occludin, E-cadherin, and zonula occludens-1 production in the colon. Furthermore, the expression of splenic cytokines such as IL-6, TNF-α, and IL-10 was up-regulated in the FWG-treated mice in a comparable amount to the control group to ensure the balance of immune responses. CONCLUSION: This study showed that the use of FWG protects the intestines from colitis caused by DSS and maintains immune balance. FWG increased antioxidant enzyme activity, increased intestinal permeability, and regulated the balance of pro- and anti-inflammatory cytokines in the intestines and spleen. Continued intake of FWG can alleviate IBD symptoms through the preservation of mucosal immune responses, epithelial junction and homeostasis through the regulated splenic cytokines. © 2021 Society of Chemical Industry.

Methylglyoxal-Derived Advanced Glycation End Products (AGE4) Promote Cell Proliferation and Survival in Renal Cell Carcinoma Cells through the RAGE/Akt/ERK Signaling Pathways.

Advanced glycation end products (AGEs) are the products formed through a non-enzymatic reaction of reducing sugars with proteins or lipids. There is a potential for toxicity in the case of AGEs produced through glycation with dicarbonyl compounds including methylglyoxal, glyoxal, and 3-deoxyglucosone. The AGEs bind the receptor for advanced glycation end products (RAGE) and stimulate the mitogen-activated protein (MAP) kinase signaling pathway that can increase the production of matrix metalloproteinases (MMPs). In addition, AGE-induced protein kinase B (Akt) signaling can promote cancer cell proliferation and contribute to many diseases such as kidney cancer. In light of the lack of extensive study of the relationship between methylglyoxal-induced AGEs (AGE4) and renal cancer, we studied the proliferous and anti-apoptotic effects of AGE4 on renal cell carcinoma (RCC) in this study. AGE4 treatment was involved in the proliferation and migration of RCC cells in vitro by upregulating proliferating cell nuclear antigen (PCNA) and MMPs while suppressing apoptotic markers such as Bax and caspase 3. Moreover, Akt and extracellular-signal-regulated kinase (ERK) were phosphorylated in RCC cells with AGE4 treatment. As a result, this study demonstrated that AGE4-RAGE axis can promote the growth ability of RCC by inducing PCNA, MMPs, and inhibiting apoptosis in RCC via the Akt and ERK signaling pathways.

Open reduction and internal fixation using multiple nonabsorbable suture materials in acute patella fracture: comparison of clinical and radiological outcome with tension band wiring.

BACKGROUND: For treating displaced patella fractures, tension band wiring is the most widely used technique. However, implant removal surgery is often necessary to alleviate discomfort caused by fixation materials. On the contrary, fixation using nonabsorbable suture materials is anticipated to result in comparable outcomes without need for further implant removal surgery. However, there is a lack of clinical studies comparing the two fixation techniques (wire and nonabsorbable suture materials) for acute patella fractures. METHODS: From 2014 to 2018, we retrospectively reviewed 60 patients who underwent open reduction with internal fixation for acute patella fracture. Thirty patients (group 1) who received surgery using tension band wiring and 30 patients (group 2) who received surgery using nonabsorbable suture materials were enrolled. The average follow-up period was more than 1 year after operation. Operation time, postoperative bone union time, range of motion (ROM) of the knee joint, postoperative clinical results, and complications were compared between the two groups. RESULT: Operation time, clinical bone union, and radiologic bone union were not statistically different between groups 1 and 2. At 3 months postoperatively, flexion was 120.3 ± 9.4° in group 1 and 110.5 ± 7.7° in group 2, showing statistically significant difference (p = 0.037). At 6 and 12 months postoperatively, the ROM was similar in both groups. Hospital for special surgery score at 3 months postoperatively was 78.4 ± 8.2 in group 1 and 83.7 ± 8.7 in group 2, showing statistically significant differences (p = 0.032). However, at 6 and 12 months postoperatively, there were no statistical differences. Lysholm score at 3 months postoperatively was 73.5 ± 8.1 in group 1 and 80.4 ± 8.2 in group 2, showing statistically significant difference (p = 0.016), but at 6 and 12 months postoperatively, there were no statistical differences. CONCLUSION: Fixation using multiple nonabsorbable suture materials can be an alternative surgical method in managing patella fractures, along with tension band wiring.

Achilles Tendon Allograft for Superior Capsule Reconstruction in Irreparable Massive Rotator Cuff Tears.

BACKGROUD: Treatment remains a challenge in massive and irreparable rotator cuff tears (RCTs), and superior capsular reconstruction (SCR) has become an increasingly popular choice. The objective of this study was to evaluate clinical and radiological outcomes after SCR using an Achilles tendon allograft in irreparable massive RCTs. METHODS: From December 2015 to March 2018, 11 patients (mean age, 66.3 ± 5.8 years) with irreparable massive RCTs who underwent SCR using an Achilles tendon allograft were enrolled in this study. The range of motion (ROM), visual analog scale (VAS), clinical scores, muscle strength, and acromiohumeral distance (AHD) were measured preoperatively and at 3, 6, and 12 months, and final follow-up postoperatively. Magnetic resonance imaging (MRI) was performed preoperatively and at 6 months postoperatively to assess the global fatty degeneration index and graft failure. Ultrasonography was also conducted preoperatively and at 3, 6, and 12 months, and final follow-up postoperatively to assess graft continuity. RESULTS: The mean follow-up period was 27.6 months (range, 24-32 months). The shoulder ROM at final follow-up increased significantly in forward flexion (p = 0.023), external rotation (p = 0.018), internal rotation (p = 0.016), and abduction (p = 0.011). All patients showed improvement in VAS score (p = 0.005) and clinical scores (p < 0.001) compared with the preoperative state. Pseudoparalysis improved in all patients. The AHD was 3.88 mm (± 1.21 mm) preoperatively, 7.75 mm (± 1.52 mm, p = 0.014) at 6 months postoperatively, and 6.37 mm (± 1.72 mm, p = 0.031) at final follow-up. Graft removal and synovectomy were performed in 1 patient who developed postoperative infections. Radiological failure on follow-up MRI occurred in 2 patients at 6 and 12 months postoperatively, respectively. CONCLUSIONS: SCR using an Achilles tendon allograft in irreparable massive RCTs achieved functional and clinical improvement. The use of Achilles tendon allograft also has the advantages of short operation time without donor site morbidity, sufficient thickness, and robustness; therefore, this allograft can be a useful graft for SCR.

Methylglyoxal-Derived Advanced Glycation End Product (AGE4)-Induced Apoptosis Leads to Mitochondrial Dysfunction and Endoplasmic Reticulum Stress through the RAGE/JNK Pathway in Kidney Cells.

Advanced glycation end products (AGEs) are formed via nonenzymatic reactions between reducing sugars and proteins. Recent studies have shown that methylglyoxal, a potent precursor for AGEs, causes a variety of biological dysfunctions, including diabetes, inflammation, renal failure, and cancer. However, little is known about the function of methylglyoxal-derived AGEs (AGE4) in kidney cells. Therefore, we verified the expression of endoplasmic reticulum (ER) stress-related genes and apoptosis markers to determine the effects of AGE4 on human proximal epithelial cells (HK-2). Moreover, our results showed that AGE4 induced the expression of apoptosis markers, such as Bax, p53, and kidney injury molecule-1, but downregulated Bcl-2 and cyclin D1 levels. AGE4 also promoted the expression of NF-κB, serving as a transcription factor, and the phosphorylation of c-Jun NH2-terminal kinase (JNK), which induced cell apoptosis and ER stress mediated by the JNK inhibitor. Furthermore, AGE4 induced mitochondrial dysfunction by inducing the permeabilization of the mitochondrial membrane and ATP synthesis. Through in vitro and in vivo experiments, this study provides a new perspective on renal dysfunction with regard to the AGE4-induced RAGE /JNK signaling pathway, which leads to renal cell apoptosis via the imbalance of mitochondrial function and ER stress in kidney damage.

Inhibitory effect of caffeic acid on advanced glycation end product-induced renal fibrosis in vitro: A potential therapeutic target.

Advanced glycation end products (AGEs) are formed from amino acids and reducing sugars through nonenzymatic Maillard reaction. AGEs are known to induce oxidative stress, which may cause fibrosis or cancer. In this study, we investigated the protective effect of caffeic acid (CA) on AGE-mediated kidney epithelial to mesenchymal transition (EMT) in human HK-2 cells. Exposure to 100 µg/mL of AGEs by kidney epithelial cells raised the production of reactive oxygen species by 5.2-fold and decreased levels of glutathione. In addition, cardamonin, a ß-catenin inhibitor, was used to determine the signaling pathway for ß-catenin in which cardamonin inhibited the AGEs-induced translocation of ß-catenin into the nucleus, resulting in an inhibition of the EMT process. Similarly, our findings showed that, close to the control level, CA treatment decreased AGE-mediated oxidative stress, loss of E-cadherin expression, and overexpression of α-smooth muscle actin and fibronectin by inactivation of the ß-catenin pathway. Furthermore, AGE treatment enhanced the expression of collagen type I (1.99-fold) as well as the activity of metalloproteinases 2 (1.86-fold) and 9 (2.79-fold), but such increase was inhibited by the pretreatment of CA. In conclusion, this study determined the inhibitory effect of CA on AGE-induced ß-catenin signaling, which prevented the occurrence of EMT in kidney epithelial cells. This suggests that CA may be a potential target for AGE-induced renal fibrosis. PRACTICAL APPLICATION: Exposure of kidney epithelial cells to advanced glycation end products (AGEs) leads to a rise in reactive oxygen species and a decrease in glutathione, thereby increasing oxidative stress that may cause fibrosis. However, treatment of kidney cells with caffeic acid (CA) prior to their exposure to AGEs lowers oxidative stress and decreases fibrosis. This research reveals the beneficial influence of CA on renal fibrosis in laboratory-cultured kidney cells (in vitro), which makes CA a potential therapeutic target for AGE-induced fibrosis.

Clinical and Radiological Outcomes after Various Treatments of Midshaft Clavicle Fractures in Adolescents.

BACKGROUD: Controversy exists about the optimal treatment of midshaft clavicle fractures in the presence of significant displacement, comminution, or shortening of the fracture in adolescents. The purpose of this study was to compare the clinical and radiological outcomes of 4 different treatments for midshaft clavicle fractures in adolescents: conservative treatment with a figure-of-8 (FO8) brace, open reduction and internal fixation with a plate (OPL), minimally invasive plate osteosynthesis (MIPO), and intramedullary nail fixation with a threaded Steinmann pin (TSP). METHODS: A total of 94 teenagers with midshaft clavicle fractures were divided into the FO8, OPL, MIPO, and TSP groups (n = 24, 33, 16, and 21, respectively). We analyzed clinical and radiological outcomes and complications in each group and compared the results among the groups. RESULTS: All groups showed satisfactory clinical and radiological outcomes, but each group showed different results for the assessment items. The Constant-Murley scores were higher in the operated groups than in the FO8 group. Recovery of joint motion was faster in the operated groups. The TSP group had the highest cosmetic satisfaction with respect to the satisfaction score and measured scar length. Fracture union was achieved in all patients. At the final follow-up, the bone length was closer to normal in the OPL and TSP groups than in the FO8 and MIPO groups, and angulation was less in the OPL and TSP groups than in the MIPO and FO8 groups. The TSP and MIPO groups obtained faster bone healing than the OPL and FO8 groups. In the operated groups, 9 patients had metal-induced irritating symptoms; 1, supraclavicular nerve injury symptoms; and 4, refractures after plate removal. CONCLUSIONS: The nonoperatively treated group had no iatrogenic complications. The operated groups complained of various disadvantages induced by surgery; however, these groups achieved faster functional recovery and slightly better radiological and functional results than the nonoperative group.

Clinical Outcome of Arthroscopic Partial Repair of Large to Massive Posterosuperior Rotator Cuff Tears: Medialization of the Attachment Site of the Rotator Cuff Tendon.

BACKGROUD: The goal of this study was to evaluate the clinical and radiological outcomes of arthroscopic partial repair with medialization of the attachment site of the rotator cuff tendon and to identify prognostic factors affecting rotator cuff healing in patients with irreparable large to massive posterosuperior rotator cuff tears. METHODS: Between July 2012 and March 2016, 42 patients with irreparable large to massive posterosuperior rotator cuff tears underwent an arthroscopic partial repair with medialization of the attachment site of the rotator cuff tendon. All patients had a minimum of 2-year follow-up (mean, 35.4 ± 7.3 months). Clinical evaluation was performed using the visual analog scale, the University of California, Los Angeles shoulder rating scale, Constant score, and active range of motion. Radiological evaluation was performed using magnetic resonance imaging and simple radiography. RESULTS: Clinical outcomes at the final follow-up improved significantly compared with the preoperative values (all p < 0.001). The failure rate was 23.8% (10/42); however, clinical outcomes significantly improved regardless of cuff healing (all p < 0.001). The mean acromiohumeral distance was 6.5 ± 1.7 mm (range, 3.2-9.7 mm) before surgery and 6.3 ± 1.6 mm (range, 2.8-9.5 mm) at the final follow-up. Preoperative acromiohumeral distance was associated with failure of cuff healing in the univariate analysis (p = 0.043) and multivariate analysis (p = 0.048). A receiver operating characteristic curve was used to determine the predictive cutoff value for the smallest preoperative acromiohumeral distance for successful healing, which was calculated as 5.3 mm. CONCLUSIONS: Despite healing failure, arthroscopic partial repair with medialization can be a possible treatment option for irreparable large to massive posterosuperior rotator cuff tears because of the improvement in clinical outcome. The shorter preoperative acromiohumeral distance was the single most important factor negatively affecting cuff healing, and the likelihood of success of healing might be improved if a repair is performed when the preoperative acromiohumeral distance is < 5.3 mm.

Synergistic Interaction of Ochratoxin A and Acrylamide Toxins in Human Kidney and Liver Cells.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium, and it is found in many foods. Acrylamide (AA) can be produced in foods treated at high temperatures. In this study, we investigated the combined toxicity of OTA and AA against human renal and hepatic cells in vitro. The concentration at which the synergistic effect of OTA and AA occurs was determined using the combination index obtained from the cell viability results for OTA and AA individually or in combination. The synergistic toxicity of both substances was evaluated by cell viability and the production of reactive oxygen species. In addition, apoptosis-related markers were significantly upregulated by OTA and AA individually or in combination. To determine the combined toxic effects of OTA and AA on the cells, the levels of enzymes involved in the phase I reaction and apoptosis-related markers were determined using quantitative (q)PCR and Western blot. The expression levels of CYP enzymes CYP1A1 and CYP1A2 involved in the phase I reaction significantly increased when the cells were treated with OTA and AA in combination. The expression of apoptosis-related markers, Bcl2-associated X protein (Bax) and caspase 3, also increased when the cells were treated with OTA and AA in combination. Therefore, the synergistic toxicity of OTA and AA suggests that such effects may contribute to nephrotoxicity and hepatotoxicity.

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic ß-Cells.

To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic ß-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 µM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of ß-cells.

Effects of Thawing and Frying Methods on the Formation of Acrylamide and Polycyclic Aromatic Hydrocarbons in Chicken Meat.

Air frying is commonly used as a substitute for deep-fat frying. However, few studies have examined the effect of air frying on the formation of potential carcinogens in foodstuffs. This study aimed to investigate the formation of acrylamide and four types of polycyclic aromatic hydrocarbons (PAHs) in air-fried and deep-fat-fried chicken breasts, thighs, and wings thawed using different methods, i.e., by using a microwave or a refrigerator, or by water immersion. The acrylamide and PAHs were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS), respectively. Deep-fat-fried chicken meat had higher acrylamide (n.d.-6.19 µg/kg) and total PAH (2.64-3.17 µg/kg) air-fried chicken meat (n.d.-3.49 µg/kg and 1.96-2.71 µg/kg). However, the thawing method did not significantly affect the formation of either acrylamide or PAHs. No significant differences in the acrylamide contents were observed among the chicken meat parts, however, the highest PAH contents were found in chicken wings. Thus, the results demonstrated that air frying could reduce the formation of acrylamide and PAHs in chicken meat in comparison with deep-fat frying.

Methylglyoxal-derived advanced glycation end products induce matrix metalloproteinases through activation of ERK/JNK/NF-κB pathway in kidney proximal epithelial cells.

The accumulation of reactive α-dicarbonyl leading to advanced glycation end products (AGEs) have been linked to pathophysiological diseases in many studies, such as atherosclerosis, cataract, cancer, and diabetic nephropathy. Glycation-generated AGEs increase the expression of inflammatory cytokines by transferring signals to the cell by binding them to the receptor for AGEs (RAGE) on their cell surface. The effect of methylglyoxal-derived AGEs (AGE-4) on the induction of matrix metalloproteinases (MMPs) in rat ordinary kidney cells (NRK-52E) was explored in this research, among other AGEs. The cell treated with 100 µg/mL AGE-4 for 24 h showed a substantial rise in MMP-2 and MMP-9 expression relative to BSA control only and other AGEs through ERK, JNK, and NF-B pathways. Our findings therefore suggest that AGE-4 expresses MMPs through the AGE-4-RAGE axis, activating MAPK signals that may contribute to dysfunction of the kidney cell.

Surgical management of an accessory canal in a maxillary premolar: a case report.

We report the surgical endodontic treatment of a maxillary first premolar with a lateral lesion that originated from an accessory canal. Although lesions originating from accessory canals frequently heal with simple conventional endodontic therapy, some lesions may need additional and different treatment. In the present case, conventional root canal retreatment led to incomplete healing with the need for further treatment (i.e., surgery). Surgical endodontic management with a fast-setting calcium silicate cement was performed on the accessory canal using a dental operating microscope. At the patient's 9-month recall visit, the lesion was resolved upon radiography.

Characterization and Immunomodulatory Effects of High Molecular Weight Fucoidan Fraction from the Sporophyll of Undaria pinnatifida in Cyclophosphamide-Induced Immunosuppressed Mice.

Immunomodulation involves two mechanisms, immunostimulation and immunosuppression. It is a complex mechanism that regulates the pathophysiology and pathogenesis of various diseases affecting the immune system. Immunomodulators can be used as immunostimulators to reduce the side effects of drugs that induce immunosuppression. In this study, we characterized the chemical composition of high molecular weight fucoidan (HMWF) and low molecular weight fucoidan and compared their functions as natural killer (NK) cell-derived immunostimulators in vitro. We also tested the effectiveness of HMWF, which has a relatively high function in vitro, as an immunostimulator in immunosuppressed animal models. In these models, HWMF significantly restored NK cell cytotoxicity and granzyme B release to the control group level. In addition, the expression of interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α also increased in the spleen. This study suggests that HMWF acts as an effective immunostimulant under immunosuppressive conditions.