Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Full-Endoscopic versus Minimally Invasive Lumbar Interbody Fusion for Lumbar Degenerative Diseases : A Systematic Review and Meta-Analysis

ObjectiveAlthough full-endoscopic lumbar interbody fusion (Endo-LIF) has been tried as the latest alternative technique to minimally invasive transforaminal lumbar interobody fusion (MIS-TLIF) since mid-2010, the evidence is still lacking. We compared the clinical outcome and safety of Endo-LIF to MIS-TLIF for lumbar degenerative disease. MethodsWe systematically searched electronic databases, including PubMed, EMBASE, and Cochrane Library to find literature comparing Endo-LIF to MIS-TLIF. The results retrieved were last updated on December 11, 2020. The perioperative outcome included the operation time, blood loss, complication, and hospital stay. The clinical outcomes included Visual analog scale (VAS) of low back pain and leg pain and Oswestry disability index (ODI), and the radiological outcome included pseudoarthosis rate with 12-month minimum follow-up. ResultsFour retrospective observational studies and one prospective observational study comprising 423 patients (183 Endo-LIF and 241 MIS-TLIF) were included, and the pooled data analysis revealed low heterogeneity between studies in our review. Baseline characteristics including age and sex were not different between the two groups. Operation time was significantly longer in Endo-LIF (mean difference [MD], 23.220 minutes; 95% confidence interval [CI], 10.669–35.771; p=0.001). However, Endo-LIF resulted in less perioperative blood loss (MD, -144.710 mL; 95% CI, 247.941–41.478; p=0.023). Although VAS back pain at final (MD, -0.120; p=0.586), leg pain within 2 weeks (MD, 0.005; p=0.293), VAS leg pain at final (MD, 0.099; p=0.099), ODI at final (MD, 0.141; p=0.093) were not different, VAS back pain within 2 weeks was more favorable in the Endo-LIF (MD, -1.538; 95% CI, -2.044 to -1.032; p<0.001). On the other hand, no statistically significant group difference in complication rate (relative risk [RR], 0.709; p=0.774), hospital stay (MD, -2.399; p=0.151), and pseudoarthrosis rate (RR, 1.284; p=0.736) were found. ConclusionRelative to MIS-TLIF, immediate outcomes were favorable in Endo-LIF in terms of blood loss and immediate VAS back pain, although complication rate, mid-term clinical outcomes, and fusion rate were not different. However, the challenges for Endo-LIF include longer operation time which means a difficult learning curve and limited surgical indication which means patient selection bias. Larger-scale, well-designed study with long-term follow-up and randomized controlled trials are needed to confirm and update the results of this systematic review.     

Establishment of Biomimetic Soft Tissue Integration with the Surface of Zirconia Fused with Platelet-Activating Peptide

Soft tissue sealing around zirconia (ZrO₂) abutment is critical for the long-term stability of dental implants. The goal of the study is to develop a strong basal lamina (BL)-mediated epithelial attachment to ZrO₂ via a novel physicochemical immobilization method. An electrophoretic fusion (EPF) method was applied to fuse a phosphonic acid (PA) linker to ZrO₂ discs. Bindings of the PA linker and the following protease activated receptor 4 (PAR4) were verified by Fourier-transform infrared spectroscopy (FITR). Then, ZrO₂ discs were doped in platelet-rich plasma (PRP). Platelet-derived growth factor (PDGF) was measured to assess platelet activation. PRP-doped discs were subsequently co-cultured with human gingival epithelial cells (OBA9) to evaluate establishment of basal lamina-mediated epithelial attachment. The EPF method achieved robust immobilization of the PA linker and PAR4 onto the ZrO₂ surface. The resultant PAR4-coupled ZrO₂ successfully induced platelet aggregation and activation. Furthermore, a BL-mediated epithelial attachment was established. The results are significant for clinical application to minimize the risk of developing peri-implant diseases.     

Rice-based breakfast improves fasting glucose and HOMA-IR in Korean adolescents who skip breakfast,but breakfast skipping increases aromatic amino acids associated with diabetes prediction in Korean adolescents who skip breakfast: a randomized,parallel-group,controlled trial

BACKGROUND/OBJECTIVESAdolescents who skip breakfast have an increased prevalence of chronic diseases. Thus, we aimed to evaluate whether the intake of rice-based breakfast had positive effects on blood glucose indices and to determine the possibility of diabetes prevalence in Korean youths who habitually skip breakfast.SUBJECTS/METHODSIn this randomized parallel-group controlled trial, 81 subjects who were suitable for compliance among 105 middle-and high-school students aged 12-18 years who usually skipped breakfast were included in this study (rice-meal group [RMG], n = 26; wheat-meal group [WMG], n = 29; general-meal group [GMG], n = 26). The RMG and WMG received a rice-based breakfast and a wheat-based breakfast for 12 weeks, respectively. The anthropometric indices, blood glucose indices, and metabolites were measured at baseline and the endpoint, respectively.RESULTSThe mean body weights in the RMG, WMG, and GMG groups at the endpoint were 62.44 kg, 61.80 kg, and 60.28 kg, respectively, and the mean body weights of the WMG and GMG groups at the endpoint were significantly higher than that at baseline (P < 0.05). The levels of fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly decreased in the RMG group at the endpoint compared to baseline (P < 0.05, P < 0.05, respectively). The levels of tryptophan and tyrosine in the WMG group at the endpoint were significantly higher than that those at baseline (P < 0.01, P < 0.05, respectively).CONCLUSIONSRice-based breakfast has positive effects on fasting insulin levels and HOMA-IR in Korean adolescents who skip breakfast. Additionally, it was found that a skipping breakfast could increase the prevalence of diabetes in adolescents who skip breakfast. Therefore, in addition to reducing breakfast skipping, it is vital to develop a rice-based menu that fits teenage preferences to prevent chronic diseases such as diabetes.Trial RegistrationClinical Research Information Service Identifier: KCT0004089     

β-Sitosterol Attenuates Dexamethasone-Induced Muscle Atrophy via Regulating FoxO1-Dependent Signaling in C2C12 Cell and Mice Model

Sarcopenia refers to a decline in muscle mass and strength with age, causing significant impairment in the ability to carry out normal daily functions and increased risk of falls and fractures, eventually leading to loss of independence. Maintaining protein homeostasis is an important factor in preventing muscle loss, and the decrease in muscle mass is caused by an imbalance between anabolism and catabolism of muscle proteins. Although β-sitosterol has various effects such as anti-inflammatory, protective effect against nonalcoholic fatty liver disease (NAFLD), antioxidant, and antidiabetic activity, the mechanism of β-sitosterol effect on the catabolic pathway was not well known. β-sitosterol was assessed in vitro and in vivo using a dexamethasone-induced muscle atrophy mice model and C2C12 myoblasts. β-sitosterol protected mice from dexamethasone-induced muscle mass loss. The thickness of gastrocnemius muscle myofibers was increased in dexamethasone with the β-sitosterol treatment group (DS). Grip strength and creatine kinase (CK) activity were also recovered when β-sitosterol was treated. The muscle loss inhibitory efficacy of β-sitosterol in dexamethasone-induced muscle atrophy in C2C12 myotube was also verified in C2C12 myoblast. β-sitosterol also recovered the width of myotubes. The protein expression of muscle atrophy F-box (MAFbx) was increased in dexamethasone-treated animal models and C2C12 myoblast, but it was reduced when β-sitosterol was treated. MuRF1 also showed similar results to MAFbx in the mRNA level of C2C12 myotubes. In addition, in the gastrocnemius and tibialis anterior muscles of mouse models, Forkhead Box O1 (FoxO1) protein was increased in the dexamethasone-treated group (Dexa) compared with the control group and reduced in the DS group. Therefore, β-sitosterol would be a potential treatment agent for aging sarcopenia.     

Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice

Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.     

Enchondral cartilage rests collagen-induced autoimmunity: a possible pathogenetic mechanism of otosclerosis

Collagen autoimmunity has been suggested as one etiologic mechanism to otosclerosis. Although substantial studies relating this disease to collagen autoimmunity have been reported, a basic understanding of the pathogenic mechanism involved is lacking. Some otosclerosis patients have a high level of antibody to type II collagen. In addition, complement and antibody were deposited in the stapes from otosclerosis patients. Furthermore, the otic capsule and stapes have been found to contain type II collagen by immunohistologic studies and biochemical analysis. Otospongiosis-like lesions have also been produced in rats by immunizing them with type II collagen. This finding led us to postulate a hypothesis of an autoimmunity to type II collagen as an etiopathogenesis of this illness. Our initial hypothesis has been updated to incorporate new findings in the field of cell biology. The role of interleukin 1, osteoclasts, osteoblasts, bone resorption, and other factors such as minor collagens, calcitonin, vitamin D, parathyroid hormone, collagenase, and prostaglandins are incorporated in this updated hypothesis.