Hydrogen Peroxide Inhibits Hepatitis B Virus Replication by Downregulating HBx Levels via Siah-1-Mediated Proteasomal Degradation in Human Hepatoma Cells.

The hepatitis B virus (HBV) is constantly exposed to significant oxidative stress characterized by elevated levels of reactive oxygen species (ROS), such as H2O2, during infection in hepatocytes of patients. In this study, we demonstrated that H2O2 inhibits HBV replication in a p53-dependent fashion in human hepatoma cell lines expressing sodium taurocholate cotransporting polypeptide. Interestingly, H2O2 failed to inhibit the replication of an HBV X protein (HBx)-null HBV mutant, but this defect was successfully complemented by ectopic expression of HBx. Additionally, H2O2 upregulated p53 levels, leading to increased expression of seven in absentia homolog 1 (Siah-1) levels. Siah-1, an E3 ligase, induced the ubiquitination-dependent proteasomal degradation of HBx. The inhibitory effect of H2O2 was nearly abolished not only by treatment with a representative antioxidant, N-acetyl-L-cysteine but also by knockdown of either p53 or Siah-1 using specific short hairpin RNA, confirming the role of p53 and Siah-1 in the inhibition of HBV replication by H2O2. The present study provides insights into the mechanism that regulates HBV replication under conditions of oxidative stress in patients.

All-trans retinoic acid inhibits HCV replication by downregulating core levels via E6AP-mediated proteasomal degradation.

Here, we found that all-trans retinoic acid (ATRA), the most biologically active metabolite of vitamin A, strengthens the anti-viral defense mechanism of E6-associated protein (E6AP) that downregulates hepatitis C virus (HCV) Core levels via ubiquitin-dependent proteasomal degradation. For this effect, ATRA downregulated both protein and enzyme activity levels of DNA methyltransferase 1 and 3b and activated E6AP expression via promoter hypomethylation in HepG2 cells but not in Hep3B cells, in which p53 was absent. Ectopic p53 expression but not E6AP overexpression restored the ability of ATRA to downregulate HCV Core levels in Hep3B cells, suggesting a direct role of p53 in the E6AP-mediated ubiquitination of HCV Core. ATRA also downregulated HCV Core levels during HCV infection in Huh7D cells to inhibit virus replication, providing theoretical basis for the clinical application of ATRA against HCV infection.

Effect of perioperative transfusion of old red blood cells on postoperative complications after free muscle sparing transverse rectus abdominis myocutaneous flap surgery for breast reconstruction.

BACKGROUND: Transfusion with old red blood cells (RBCs) was associated with adverse clinical outcomes. The effect of perioperative transfusion of old RBCs on postoperative complications after free muscle sparing transverse rectus abdominis myocutaneous (TRAM) flap surgery was retrospectively investigated. METHODS: Two hundred sixty-one patients undergoing breast reconstruction were assigned to two groups: no transfusion and transfusion groups. Transfused patients were further divided according to the RBC storage duration (fresh, ≤14 days; old, >14 days). Postoperative complications such as vascular thrombosis, hematoma, and flap congestion were noted. RESULTS: Patients who received old blood (n = 34), compared with those received fresh blood (n = 40) or no transfusion (n = 187), had a higher incidence of postoperative complications (44.1% vs. 20.0% or 12.8%, P < 0.05). CONCLUSIONS: Perioperative transfusion of old RBCs can be associated with an increase in postoperative complications after free muscle sparing TRAM flap surgery.

Therapeutic singing-induced swallowing exercise for dysphagia in advanced-stage Parkinson's disease.

Background: With longer life spans and medical advancements, the rising number of patients with advanced-stage Parkinson's disease (PD) warrants attention. Current literature predominantly addresses dementia and fall management in these patients. However, exploring the impact of swallowing function on patients with advanced PD is crucial. Previous research has demonstrated notable enhancements in the quality of life related to voice for participants following a group singing-intervention program. To further elucidate the effect of individual singing-induced swallowing exercises, our study aimed to investigate the quantitative and qualitative effects of therapeutic singing on swallowing function in patients with advanced PD in comparison to a matched usual care control group. The hypothesis of this study is that therapeutic singing-induced swallowing exercises can assist to maintain swallowing function in patients with advanced PD. Methods: This prospective matched control study compared the effects of a 6-week therapeutic singing-based swallowing intervention on swallowing function and quality of life in patients with advanced PD. The intervention group received individual sessions with a music therapist and conventional individual physical therapy. The control group received the same standard physical therapy for 6 weeks without music intervention. The primary outcome measure was Video Fluoroscopic Dysphagia Scale (VDS). Results: The study revealed that the intervention group maintained swallowing function, whereas the control group experienced deterioration, indicating significant time-dependent changes in Penetration-Aspiration Scale (PAS), National Institutes of Health-Swallowing Safety Scale (NIH-SSS), and VDS. Analysis of PAS and NIH-SSS liquid food scores in both groups showed significant time effects. However, the intervention group exhibited no significant differences between the pre- and post-tests, indicating preservation of the swallowing function. VDS of liquid food indicated an interaction effect between time and group in the pharyngeal phase and total scores. The Swallowing-Quality of Life showed significant time-effect improvement in the intervention group. Conclusion: Therapeutic singing exercises may help maintain swallowing function in advanced PD patients, potentially enhancing quality of life related to swallowing in those with advanced-stage diseases. Clinical trial registration: https://cris.nih.go.kr/cris/search/listDetail.do, identifier KCT0008644.

Beneficial effects of fresh and fermented kimchi in prediabetic individuals.

BACKGROUND: With the increased incidence of diabetes mellitus, the importance of early intervention in prediabetes has been emphasized. We previously reported that fermented kimchi, a traditional Korean food, reduced body weight and improved metabolic factors in overweight participants. We hypothesized that kimchi and its fermented form would have beneficial effects on glucose metabolism in patients with prediabetes. METHODS: A total of 21 participants with prediabetes were enrolled. During the first 8 weeks, they consumed either fresh (1-day-old) or fermented (10-day-old) kimchi. After a 4-week washout period, they switched to the other type of kimchi for the next 8 weeks. RESULTS: Consumption of both types of kimchi significantly decreased body weight, body mass index, and waist circumference. Fermented kimchi decreased insulin resistance, and increased insulin sensitivity, QUICKI and disposition index values (p = 0.004 and 0.028, respectively). Systolic and diastolic blood pressure (BP) decreased significantly in the fermented kimchi group. The percentages of participants who showed improved glucose tolerance were 9.5 and 33.3% in the fresh and fermented kimchi groups, respectively. CONCLUSIONS: Consumption of kimchi had beneficial effects on glucose metabolism-related and anthropometric factors in participants with prediabetes. Fermented kimchi had additional effects on BP and insulin resistance/sensitivity. The percentage of participants who showed improvement in glucose tolerance was high in the fermented kimchi group.

Clinical significance of the cross-sectional area of the internal jugular vein.

OBJECTIVES: The aim of this study was to compare the cross-sectional area (CSA) of the right internal jugular vein (IJV) with that of the left IJV and to evaluate the anatomic location of the IJV in relation to the common carotid artery, utilizing computed tomography scans of the neck. DESIGN: Retrospective observational study. SETTING: A tertiary care hospital. PARTICIPANTS: Eighty patients with neck computed tomography scans scheduled for thyroid surgery. INTERVENTION: No. MEASUREMENTS AND MAIN RESULTS: Mean CSA of the right and left IJV were 165±81 and 119±57 mm(2), respectively (p<0.01). A relatively larger CSA of the right IJV, compared with that of the left , was seen in 63 (79%) patients. A larger CSA of the right IJV was shown in more right-handed subjects than left-handed subjects (82 v 43%, p<0.05). Small CSA (<50 mm(2)) of the right or left IJV were seen in 4 patients. Both IJVs were located commonly either laterally or anterolaterally to their common carotid arteries. A posterolateral position of the IJV was seen in 4 patients. CONCLUSIONS: This study suggested one advantage of using the right IJV compared with the left for central venous cannulation. However, anatomic variations of the IJV, such as a small CSA and a medial or posterior position, are not associated with demographic data. Although right-handedness was well-correlated with a larger ipsilateral IJV, a possibility of a larger contralateral IJV should be considered. Therefore, central venous cannulation with ultrasonography is recommended to avoid complications and repeated needling.

Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration.

Bone remodeling process relies on complex signaling pathway between osteoblasts and osteoclasts and control mechanisms to achieve homeostasis of their growth and differentiation. Despite previous achievements in understanding complicated signaling pathways between cells and bone extracellular matrices during bone remodeling process, a role of local ionic concentration remains to be elucidated. Here, we demonstrate that synthetic whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) nanoparticles can recapitulate early-stage of bone regeneration through stimulating osteogenic differentiation, prohibiting osteoclastic activity, and transforming into mechanically enhanced hydroxyapatite (HAP)-neo bone tissues by continuous supply of PO43- and Mg2+ under physiological conditions. In addition, based on their structural analysis, the dynamic phase transformation from WH into HAP contributed as a key factor for rapid bone regeneration with denser hierarchical neo-bone structure. Our findings suggest a groundbreaking concept of 'living bone minerals' that actively communicate with the surrounding system to induce self-healing, while previous notions about bone minerals have been limited to passive products of cellular mineralization.

In Vitro and In Vivo Evaluation of Whitlockite Biocompatibility: Comparative Study with Hydroxyapatite and ß-Tricalcium Phosphate.

Biomimicking ceramics have been developed to induce efficient recovery of damaged hard tissues. Among them, calcium phosphate-based bioceramics have been the most widely used because of their similar composition with human hard tissue and excellent biocompatibilities. However, the incomplete understanding of entire inorganic phases in natural bone has limited the recreation of complete bone compositions. In this work, broad biomedical evaluation of whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12), which is the secondary inorganic phase in bone, is conducted to better understand human hard tissue and to seek potential application as a biomaterial. Based on the recently developed gram-scale method for synthesizing WH nanoparticles, the properties of WH as a material for cellular scaffolding and bone implants are assessed and compared to those of hydroxyapatite (HAP: Ca10(PO4)6(OH)2) and ß-tricalcium phosphate (ß-TCP: ß-Ca3(PO4)2). WH-reinforced composite scaffolds facilitate bone-specific differentiation compared to HAP-reinforced composite scaffolds. Additionally, WH implants induce similar or better bone regeneration in calvarial defects in a rat model compared to HAP and ß-TCP implants, with intermediate resorbability. New findings of the properties of WH that distinguish it from HAP and ß-TCP are significant in understanding human hard tissue, mimicking bone tissue at the nanoscale and designing functional bioceramics.

Effect and appropriate restriction period of constraint-induced movement therapy in hemiparetic patients with brain injury: a brief report.

OBJECTIVE: To investigate the effect on fine motor ability and the appropriate restriction period of constraint-induced movement therapy in hemiparetic patients with brain injury. DESIGN: Nine chronic hemiparetic patients with brain injury were studied. After confirming the cessation of further recovery of fine motor ability by Purdue pegboard test and motor function by the Medical Research Council for three consecutive weeks, the affected hand was restricted with an opposition restriction orthosis. The fine motor ability of the affected hand was assessed weekly using Purdue pegboard test and the orthosis was taken off when the Purdue pegboard score showed no further increase over three consecutive weeks. RESULTS: Purdue pegboard score increased in all patients. The mean post-treatment Purdue pegboard score (10.7) was significantly increased over that of pre-treatment (8.7) (p < 0.05). The mean restriction period was 3.6 weeks (range, 2 to 5 weeks). CONCLUSION: Constraint-induced movement therapy is an effective therapeutic method to improve the fine motor ability of the hemiparetic hand of brain-injured patients. It can be assumed that the appropriate restriction period is best decided individually, on a case by case basis, according to the time that maximizes the hand function of the affected hand.

Screening and Characterization of Lactic Acid Bacteria Strains with Anti-inflammatory Activities through in vitro and Caenorhabditis elegans Model Testing.

The present study was conducted to screen candidate probiotic strains for anti-inflammatory activity. Initially, a nitric oxide (NO) assay was used to test selected candidate probiotic strains for anti-inflammatory activity in cultures of the murine macrophage cell line, RAW 264.7. Then, the in vitro probiotic properties of the strains, including bile tolerance, acid resistance, and growth in skim milk media, were investigated. We also performed an in vitro hydrophobicity test and an intestinal adhesion assay using Caenorhabditis elegans as a surrogate in vivo model. From our screening, we obtained 4 probiotic candidate lactic acid bacteria (LAB) strains based on their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell cultures and the results of the in vitro and in vivo probiotic property assessments. Molecular characterization using 16S rDNA sequencing analysis identified the 4 LAB strains as Lactobacillus plantarum. The selected L. plantarum strains (CAU1054, CAU1055, CAU1064, and CAU1106) were found to possess desirable in vitro and in vivo probiotic properties, and these strains are good candidates for further investigations in animal models and human clinical studies to elucidate the mechanisms underlying their anti-inflammatory activities.

Phase transformation from hydroxyapatite to the secondary bone mineral, whitlockite.

Whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) is the second most abundant mineral in hard tissues, but its precipitation mechanism or role in the body system is poorly understood. Here, using a newly discovered synthetic method for WH, we investigated the kinetic mechanism for the precipitation of WH under physiologically similar conditions, excluding any effects of toxic ions. Based on systematically classified stages in the precipitation process of WH, we monitored the transformation of calcium phosphate phases from neutral pH to acidic pH with the addition of H3PO4. The study revealed that at 70 °C, hydroxyapatite (HAP: Ca10(PO4)6(OH)2) transforms into dicalcium phosphate dihydrate (DCPD: CaHPO4·2H2O) and then into WH in the presence of Mg2+ ions as the pH decreases. The transformation process involves multiple intermediates, the stability of which depends on the cation (Ca and Mg) activities and the solution pH. WH is the most stable calcium phosphate compound below pH 4.2, whereas HAP is the most stable around neutral pH. We also found that Mg2+ ions, which are known to block the growth of HAP, can play a key role in WH formation. This study provides a new insight into the interplay of biologically important calcium phosphate compounds.

Biofunctionalized ceramic with self-assembled networks of nanochannels.

Nature designs circulatory systems with hierarchically organized networks of gradually tapered channels ranging from micrometer to nanometer in diameter. In most hard tissues in biological systems, fluid, gases, nutrients and wastes are constantly exchanged through such networks. Here, we developed a biologically inspired, hierarchically organized structure in ceramic to achieve effective permeation with minimum void region, using fabrication methods that create a long-range, highly interconnected nanochannel system in a ceramic biomaterial. This design of a synthetic model-material was implemented through a novel pressurized sintering process formulated to induce a gradual tapering in channel diameter based on pressure-dependent polymer agglomeration. The resulting system allows long-range, efficient transport of fluid and nutrients into sites and interfaces that conventional fluid conduction cannot reach without external force. We demonstrate the ability of mammalian bone-forming cells placed at the distal transport termination of the nanochannel system to proliferate in a manner dependent solely upon the supply of media by the self-powering nanochannels. This approach mimics the significant contribution that nanochannel transport plays in maintaining living hard tissues by providing nutrient supply that facilitates cell growth and differentiation, and thereby makes the ceramic composite "alive".

Severe neurologic manifestations in acute intermittent porphyria developed after spine surgery under general anesthesia: a case report.

Porphyrias are inherited metabolic disorders resulting from a specific enzyme defect in the heme biosynthetic pathway. Porphyrias are induced by various precipitants. Clinical features include abdominal pain, neurologic manifestations, autonomic neuropathy, and mental disturbance. Diagnosis may be delayed because of variable symptoms that mimic other diseases and because of the rarity of of porphyrias. Although most patients with known porphyria can complete anesthesia and surgery safely, undiagnosed porphyric patients are in danger of porphyric crisis due to inadvertent exposure to precipitating drugs and environment. We report a case of a patient who experienced delayed emergence with neurological disturbance after general anesthesia, ultimately diagnosed as acute intermittent porphyria.

Anesthetic management for a patient with severe mento-sternal contracture: difficult airway and scarce venous access -A case report-.

There are many problems in the anesthetic management of patients with scar contracture. In this case, a 41-year-old male with severe scar contracture on his face, neck, anterior chest, and both shoulders underwent surgery for resurfacing with flaps. We tried to awake fiberoptic orotracheal intubation with GlideScope® Video laryngoscope guide after surgical release of contracture under local anesthesia. We report a successful management of a patient with severe burn contracture achieved by combined effort of surgeons and anesthesiologists.

The postoperative C-reactive protein level can be a useful prognostic factor for poor outcome and symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Ninety-three patients undergoing surgical or endovascular operation secondary to aneurysmal subarachnoid hemorrhage (SAH) were retrospectively analyzed to determine the influence of the different time points of C-reactive protein (CRP) measurement on the prediction of vasospasm and clinical outcome. METHODS: Laboratory data such as the CRP level and the white blood cell count, preoperative demographic and clinical data, intraoperative and postoperative data, and complications such as intracerebral hemorrhage, hydrocephalus, vasospasm, and surgical decompression were collected at hospital discharge or symptomatic vasospasm and used as predictable factors for poor outcome (Modified Rankin Scale score 4 to 6). RESULTS: Twenty-three and 28 patients showed poor outcome and symptomatic vasospasm after SAH, respectively. Both preoperative and postoperative CRP levels were significantly higher in patients with a poor outcome compared with patients with a good outcome (P<0.05). The area under the receiver operating characteristic curve of CRP measured on postoperative day 1 or 2 (CRP POD1-2) for predicting a poor clinical outcome was 0.870, and its cutoff point of 4 mg/dL had a sensitivity of 0.826 and a specificity of 0.843. A high CRP level after aneurysm treatment was associated with severe neurological deterioration on admission, cerebral infarction, intracerebral hemorrhage, and surgical decompression (P<0.05). CRP POD1-2, and not the preoperative CRP, was an independent factor in predicting symptomatic vasospasm (P<0.05). In patients with symptomatic vasospasm, an increase in the postoperative CRP was associated with the time profile of developing symptomatic vasospasm. CONCLUSION: Postoperative CRP, especially CRP POD1-2, can be a useful prognostic factor for both poor outcome and symptomatic vasospasm in patients with aneurysmal SAH.

Intake of brown rice lees reduces waist circumference and improves metabolic parameters in type 2 diabetes.

Intake of whole grains has been associated with lower risks of type 2 diabetes and cardiovascular disease. Brown rice is unrefined whole grain and is produced by removing the outermost layers containing the germ and bran, which are rich in nutrients including dietary fiber, vitamins, minerals, and other unmeasured dietary constituents. The lees of brown rice (LB) are by-products of its fermentation in the process of manufacturing takju, a Korean turbid rice wine. In this study, we hypothesized that intake of LB would reduce waist circumference, a strong risk factor for cardiovascular disease in type 2 diabetic patients. A randomized, double-blind, placebo-controlled study was scheduled for 12 weeks. Thirty subjects were randomly assigned to receive a supplement prepared from the LB or from a mixed-grain dietary product (MG). Body weight, waist circumference, body composition, lipid profiles, and other laboratory parameters were measured. The LB group showed greater reduction in waist circumference (LB: 87.9 ± 8.8 to 85.1 ± 9.0 cm; MG: 86.9 ± 8.8 to 86.0 ± 9.3 cm; P = .032). In addition, the consumption of LB resulted in a significantly greater decrease in the level of aspartate transaminase (LB: 25.4 ± 8.5 to 21.0 ± 5.1 IU/mL; MG: 22.5 ± 5.3 to 22.4 ± 5.7 IU/mL; P = .044) and alanine transaminase (LB: 28.6 ± 11.3 to 21.9 ± 8.2 IU/mL; MG: 24.4 ± 7.5 to 24.5 ± 9.9 IU/mL; P = .038). Consumption of the LB was associated with a decreased waist circumference in type 2 diabetic patients. Further study is required to evaluate the metabolic effect of the extract of the LB in type 2 diabetes.

Fermented kimchi reduces body weight and improves metabolic parameters in overweight and obese patients.

Kimchi is a traditional fermented Korean food that has garnered international interest due to its various beneficial effects. Focusing on the effect of fermentation, this study hypothesized that consumption of fermented kimchi would have more beneficial effects compared with that of fresh kimchi on metabolic parameters that are related to cardiovascular disease and metabolic syndrome risks in overweight and obese subjects. Twenty-two overweight and obese patients with body mass indexes greater than 25 kg/m(2) were randomly assigned to two 4-week diet phases separated by a 2-week washout period (crossover design). During each diet phase, the subjects consumed either fresh or fermented kimchi. Anthropometric data showed significant decreases in body weight, body mass index, and body fat in both groups, and the fermented kimchi group showed a significant decrease in the waist-hip ratio and fasting blood glucose. Net differences in the systolic blood pressure, diastolic blood pressure, percent body fat, fasting glucose, and total cholesterol in the fermented kimchi group were significantly greater than those in the fresh kimchi group. There was also a tendency for a decrease in fasting insulin after consumption of fermented kimchi. Therefore, the ingestion of fermented kimchi had positive effects on various factors associated with metabolic syndrome, including systolic and diastolic blood pressures, percent body fat, fasting glucose, and total cholesterol, compared with the fresh kimchi. These results suggest that the maturity of kimchi (fresh vs fermented) may affect obesity, lipid metabolism, and inflammatory processes.