Lactococcus lactis KF140 Ameliorates Nonalcoholic Fatty Liver Disease Induced by Nε-Carboxymethyl-Lysine and High-Fat Diet.

SCOPE: Long-term consumption of excessive dietary advanced glycation end-products such as Nε-carboxymethyl-lysine (CML), which are produced by the Maillard reaction during food thermal processing, leads to nonalcoholic fatty liver disease (NAFLD) along with high fat consumption. The study previously finds that administration of Lactococcus lactis KF140 (LL-KF140) detoxifies CML by decreasing CML absorption both in a rat model and clinical trial. METHODS AND RESULTS: The present study evaluates the ameliorative effect of LL-KF140 on NAFLD and fatty liver-related biomarkers in a mouse model induced by CML and high fat. LL-KF140 is orally administered to mice at a concentration of 1 × 107 or 1 × 108 colony-forming unit (CFU) per mouse for 8 weeks. LL-KF140 administration ameliorates the NAFLD-related symptoms by reducing body weight and fat mass gain along with levels of serum aspartate transaminase, alanine transferase, and lipids as well as glucose intolerance and insulin resistance in CML-treated mice. In addition, histological analysis including staining and western blotting shows that LL-KF140 suppresses the lipogenesis pathway and CML absorption, thereby suppressing CML-induced NAFLD. CONCLUSION: These findings suggest that LL-KF140 attenuates dietary CML-induced NAFLD by suppressing the de novo lipogenesis pathway, and it may be used as a probiotic strain.

Evaluation of the root dentin bond strength and intratubular biomineralization of a premixed calcium aluminate-based hydraulic bioceramic endodontic sealer.

PURPOSE: This study evaluated the dentin bonding strength and biomineralization effect of a recently developed premixed calcium aluminate-based endodontic sealer (Dia-Root Bio Sealer) in comparison with existing calcium silicate-based sealers. METHODS: The root canals of 80 mandibular premolars were filled with Dia-Root Bio Sealer, Endoseal MTA, EndoSequence BC Sealer, and AH Plus Bioceramic Sealer. Medial and apical specimens were then obtained by sectioning. The push-out bond strength was measured using the medial specimens, and the failure mode was recorded. Intratubular biomineralization in the apical specimens was analyzed using scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS). The data were analyzed using one-way analysis of variance followed by the Tukey test (P < 0.05). RESULTS: The push-out bond strength of Dia-Root Bio Sealer was significantly higher than that of the other tested materials, and a cohesive failure pattern was observed in all groups. Dia-Root Bio Sealer also exhibited a significantly higher degree of biomineralization than the other groups, and EDS analysis indicated that the biomineralized precipitates were amorphous calcium phosphate. CONCLUSION: The results of this study indicate that Dia-Root Bio Sealer has the potential to be used as an adequate root canal sealer due to its favorable bonding performance.

Identifying high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips: Impact of cooking parameters, including temperature, time, presoaking, and seasoning.

This study was conducted to identify high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips by studying the impact of various cooking parameters, including temperature, time, presoaking, and pre-seasoning treatments. The temperature and time had a surprisingly high impact on acrylamide formation. The chips prepared at high temperatures with longer cooking times contained an extremely high acrylamide content, reaching 12,786 ng/g (e.g., 170°C/19 min). A particularly concerning discovery was that the chips with extremely high acrylamide content (up to 17 times higher than the EU benchmark level for potato chips) did not appear overcooked or taste burnt. Higher cooking temperatures required shorter cooking times to properly cook lotus root chips for consumption. A high temperature with a short cooking time (170°C/13 min) greatly benefited acrylamide reduction compared to low temperature with a long cooking time (150°C/19 min). Presoaking in a 0.1% acetic acid solution and pre-seasoning with 1% salt reduced acrylamide levels by 61% and 47%, respectively. However, presoaking in water, vinegar solution, and citric acid solution did not significantly decrease the acrylamide content in the chips. Furthermore, some seasonings significantly increased acrylamide levels (up to 7.4 times higher). For the first time, these findings underscore the high risks associated with air-frying lotus root chips without considering these factors. This study also provides proper air-frying parameters and pretreatment strategies for minimizing acrylamide formation in air-fried lotus chips.

Surface property changes observed in zirconia during etching with high-concentration hydrofluoric acid over various immersion times.

This study investigated the degree of phase transformation, surface roughness, and bond strength of zirconia immersed for various times in a 40% hydrofluoric acid (HF) solution. Non-etched sintered zirconia specimens were used as the control, while experimental groups were etched with a 40% HF solution for 5, 10, 20, 40, 80, 160 and 320 min. In each of the control and experimental groups, five specimens for X-ray diffraction analysis, four for surface morphology and surface roughness analysis, and ten for bonding strength measurement were used. As a result, the surface roughness of zirconia increased as the application time increased during the 40% HF etching, but the bond strength between zirconia and resin cement did not increase proportionally. The phase transformation from tetragonal to monoclinic also gradually increased with application time.

Heavy metal concentration according to shrimp species and organ specificity: Monitoring and human risk assessment.

This study assessed heavy metal levels (lead (Pb), cadmium (Cd), total arsenic (tAs), arsenite (As (III)), arsenate (As (V)), monomethyl arsenic acid (MMA), dimethylarsinic acid (DMA), total mercury (tHg), and methylmercury (MeHg)) in six organs (total portion, head, body, shell, muscle, and intestine) of 11 shrimp species distributed in Korea. Shrimp exhibited significant variability in heavy metal accumulation, with Alaskan pink and dried shrimp (Lesser glass, Southern rough, and Chinese ditch prawn) showing the highest metal concentrations. Notably, the intestine having the highest overall metal content, while Cd was most prominent in the head, tHg was highest in the muscle. The Hazard Quotient values of 11 shrimp species in South Korea were below the European Food Safety Authority's allowable limits for heavy metals. This study illuminates the heavy metal profiles of distributed shrimp in Korea and emphasizes the ongoing need for monitoring heavy metals on seafood to ensure consumer safety.

Dietary Nε-(carboxymethyl)lysine is a trigger of non-alcoholic fatty liver disease under high-fat consumption.

The irreversible glycation of proteins produces advanced glycation end products (AGEs) which are triggered to bind the receptor for AGE (RAGE), thereby activating mitogen-activated protein kinase/nuclear factor-κB signaling pathway and stimulating proinflammatory cytokines, ultimately leading to chronic disorders. In this study, we focus the promoting effect of Nε-carboxymethyl-lysine (CML), one of the most dietary AGEs, on non-alcoholic fatty liver disease (NAFLD) and evaluated NAFLD-related biomarkers. Oxidative stress and hepatic steatosis were assessed in oleic acid (OA)-induced HepG2 cells. Using OA-induced HepG2 cells, we show that CML results in oxidative stress and steatosis and drives major changes in hepatic lipid metabolism. Administration of CML exacerbated NAFLD-related symptoms by increasing body and liver weight gain, serum alanine aminotransferase and lipid levels, and insulin resistance in mild high-fat diet-induced mice. Moreover, hepatic histological analysis data, such as staining, western blotting, and RNA-seq, indicate that CML aggravates NAFLD in association with activation of the de novo lipogenesis pathway, consistent with the in vitro assays. Our findings could contribute to model studies related to the prevention and treatment of NAFLD progression due to excessive consumption of dietary AGEs.

Monitoring arsenic species concentration in rice-based processed products distributed in South Korean markets and related risk assessment.

Rice is an important grain as a major source of carbohydrates in Asia but contains more arsenic (As) than other grains. A total of 239 rice-based processed foods (rice, n = 30; rice cake, n = 30; porridge, n = 39; noodles, n = 33; bread, n = 20; snack, n = 59; powder, n = 28) were purchased in 2019 from domestic markets to measure total As (tAs) and As species. The average tAs and inorganic As (iAs) in each sample group ranged from 20 to 180 µg/kg (porridge for baby to noodle) and 4.4-85 µg/kg (porridge for baby to powder), respectively. The correlation between the iAs and tAs was affected by the variety of ingredients, such as the presence of seaweed (tAs) and the milling type of rice (iAs). Although rice cakes and baby rice-based powders are a source of concern for both adults and children, respectively, risk assessments indicate that most rice-based foods are generally safe to consume in South Korea. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01270-9.

MiR-155-5p Elevated by Ochratoxin A Induces Intestinal Fibrosis and Epithelial-to-Mesenchymal Transition through TGF-ß Regulated Signaling Pathway In Vitro and In Vivo.

Ochratoxin A (OTA) is a mycotoxin that induces fibrosis and epithelial-to-mesenchymal transitions (EMT) in kidneys and livers. It enters our bodies through food consumption, where it is absorbed in the intestines. However, the impact of OTA on the intestines is yet to be studied. MicroRNA (miRNAs) are small non-coding single-stranded RNAs that block the transcription of specific mRNAs and are, therefore, involved in many biochemical processes. Our findings indicate that OTA can induce EMT and intestinal fibrosis both in vivo and in vitro. This study examines the impact of OTA on intestinal toxicity and the role of miRNAs in this process. Following OTA treatment, miR-155-5p was the most elevated miRNA by next-generation sequencing. Our research showed that OTA increased miR-155-5p levels through transforming growth factor ß (TGF-ß), leading to the development of intestinal fibrosis and EMT. Additionally, the study identified that the modulation of TGF-ß and miR-155-5p by OTA is linked to the inhibition of CCAAT/enhancer-binding protein ß (C/EBPß) and Smad2/3 accumulation in the progression of intestinal fibrosis.

Perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide-dimer acid (GenX): Hepatic stress and bile acid metabolism with different pathways.

Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms.

Biomechanical impact of elbow motion in elbow stiffness.

BACKGROUND: A mechanical block in the elbow due to osteophytes in the olecranon fossa is a common clinical symptom for elbow stiffness. PURPOSE/HYPOTHESIS: This study aims to understand the biomechanical characteristics or changes in the stiff elbow in the resting (or neutral) and swing position of the arm using a cadaveric model. The hypotheses included the following: (1) a difference exists in the articular contact pressure of the elbow by comparing the non-stiff and stiff models in in vivo studies; (2) the degree of stiffness would affect the increase of the joint loading of the elbow. STUDY DESIGN: Controlled laboratory study, cadaveric study. METHODS: Eight fresh-frozen specimens from individuals of both sexes were included in the biomechanical study. The specimen was mounted on a custom-designed jig system with gravity-assisted muscle contracture to mimic the elbow in a standing position. The elbow was tested in two conditions (the resting and passive swing). Contact pressure was recorded for three seconds in the resting position, which was the neutral position of the humerus. By dropping the forearm from 90° of the elbow flexion, the passive swing was performed. The specimens were tested sequentially in three stages of stiffness (stage 0, no stiffness; stage 1, 30° of extension limitation; and stage 2, 60° of extension limitation). After data collection was completed in stage 0, a stiff model was sequentially created for each stage. The stiff model of the elbow was created by blocking the olecranon by inserting a 2.0 K-wire into the olecranon fossa horizontally with the intercondylar axis. RESULTS: The mean contact pressures were 279 ± 23, 302 ± 6, and 349 ± 23 kPa in stages 0, 1, and 2, respectively. The increases in the mean contact pressure in stages 2 versus 0 were significant (P < 0.0001). The mean contact pressures were 297 ± 19, 310 ± 14, and 326 ± 13 kPa in stages 0, 1, and 2, respectively. The peak contact pressures were 420 ± 54, 448 ± 84, and 500 ± 67 kPa in stages 0, 1, and 2, respectively. The increases in mean contact pressure in stage 2 versus 0 were significant (P = 0.039). The increases in peak contact pressure in stages 0 versus 2 were significant (P = 0.007). CONCLUSIONS: The elbow bears the load created by gravity and muscle contracture in the resting and swing motion. Moreover, extension limitation of stiff elbow increases the load bearing in the resting position and swing motion. Careful surgical management should be considered for meticulous clearance of bony spur around olecranon fossa to resolve the extension limitation of the elbow.

Push-out bond strength and intratubular biomineralization of a hydraulic root-end filling material premixed with dimethyl sulfoxide as a vehicle.

Objectives: This study was designed to evaluate the parameters of bonding performance to root dentin, including push-out bond strength and dentinal tubular biomineralization, of a hydraulic bioceramic root-end filling material premixed with dimethyl sulfoxide (Endocem MTA Premixed) in comparison to a conventional powder-liquid-type cement (ProRoot MTA). Materials and Methods: The root canal of a single-rooted premolar was filled with either ProRoot MTA or Endocem MTA Premixed (n = 15). A slice of dentin was obtained from each root. Using the sliced specimen, the push-out bond strength was measured, and the failure pattern was observed under a stereomicroscope. The apical segment was divided into halves; the split surface was observed under a scanning electron microscope, and intratubular biomineralization was examined by observing the precipitates formed in the dentinal tubule. Then, the chemical characteristics of the precipitates were evaluated with energy-dispersive X-ray spectroscopic (EDS) analysis. The data were analyzed using the Student's t-test followed by the Mann-Whitney U test (p < 0.05). Results: No significant difference was found between the 2 tested groups in push-out bond strength, and cohesive failure was the predominant failure type. In both groups, flake-shaped precipitates were observed along dentinal tubules. The EDS analysis indicated that the mass percentage of calcium and phosphorus in the precipitate was similar to that found in hydroxyapatite. Conclusions: Regarding bonding to root dentin, Endocem MTA Premixed may have potential for use as an acceptable root-end filling material.

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.

Ochratoxin A induces endoplasmic reticulum stress and fibrosis in the kidney via the HIF-1α/miR-155-5p link.

Ochratoxin A (OTA) is a ubiquitous fungal toxin found in agricultural products and foods that is toxic to both humans and animals. OTA mainly affects kidney, but the mechanisms underlying OTA-induced nephrotoxicity remain not fully understood. MicroRNA (miRNA) is involved in key cellular processes. The toxic mechanism and regulatory effects of miRNAs on OTA toxicity in kidney, and particularly the role of HIFα-1/miR-155-5p on OTA-caused ER stress and fibrosis, were investigated in this study. OTA induced hypoxia-like conditions such as ER stress and fibrosis in HK-2 cells and renal tissues via modulating HIF-1α, which was followed by regulation of ER stress-related proteins (GRP78 and ATF-4), as well as fibrosis-related markers (fibronectin, α-SMA, and E-cadherin). Notably, a total of 62 miRNAs showed significant differential expression in kidney of OTA-treated mice. Under OTA exposure, HIF-1α enhanced miR-155-5p expression, causing ER stress and fibrosis in HK-2 cells. HIF-1α knockdown decreased OTA-induced miR-155-5p expression as well as ER stress and fibrotic responses, whereas miR-155-5p overexpression restored this. Our data suggest that OTA enhances ER stress and fibrosis in the kidney through upregulating the HIF-1α/miR-155-5p link.

Glyoxal-derived advanced glycation end-products, Nε-carboxymethyl-lysine, and glyoxal-derived lysine dimer induce apoptosis-related gene expression in hepatocytes.

BACKGROUND: Advanced glycation end-products (AGEs) are proteins or lipids that have been glycated nonenzymatically by reducing sugars and their derivatives such as methylglyoxal. AGEs are known to cause inflammation, oxidative stress, and diseases in the human body. The toxic effects of AGEs and their structures on the origin of the protein being modified have not been well studied. METHODS AND RESULTS: Five different types of AGEs: AGE1 (glucose-derived), AGE2 (glyceraldehyde-derived), AGE3 (glycolaldehyde-derived), AGE4 (methylglyoxal-derived), and AGE5 (glyoxal-derived); were used to examine the effect of AGEs on HepG2 cells. AGE2 through 5 increase the production of reactive oxygen species (ROS) in liver cells, an initiating factor for apoptosis. At the mRNA and protein levels, AGE5 treatment showed the greatest increase in expression of apoptosis-related factors such as Bax, p53, and Caspase 3. Quantitative analysis revealed that Nε-carboxymethyl-lysine (CML) and glyoxal-lysine dimer (GOLD) were the important types of AGE5. The ROS generation and the expression of apoptotic factors both increased when cells were treated with CML and GOLD. CONCLUSION: These findings suggest that AGE5 treatment activates the apoptosis-related gene expression in hapatocytes, with CML and GOLD as potential major AGE compounds.

Effects of barium titanate on the dielectric constant, radiopacity, and biological properties of tricalcium silicate-based bioceramics.

This study evaluated the effect of barium titanate (BT) on the dielectricity, radiopacity, and biological properties of tricalcium silicate (C3S). C3S/BT samples were prepared with varying proportions of BT (0, 20, 40, and 60 wt%; referred to as BT00, BT20, BT40, and BT60, respectively). Dielectric constant and radiopacity were measured. Cytocompatibility was evaluated on human dental pulp cells. After surgical procedures on rat mandible, immunohistochemistry and Masson's trichrome staining were performed. The dielectric constant increased with higher proportions of BT (p<0.05). BT40 and BT60 satisfied the clinical guideline of radiopacity. There were no significant differences among groups in the cytocompatibility tests (p>0.05). New bone was observed well, along with the expressions of the dentin matrix protein 1 (DMP1), osteocalcin (OC), and osteonectin (ON) in BT40 and BT60. Conclusively, the contents of 40-60 wt% of BT in C3S provided proper radiopacity, favorable cytocompatibility, and beneficial effect on bone regeneration.

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.