Does the proximal humeral bone quality influence alignment after reverse total shoulder arthroplasty with short humeral stems?

PURPOSE: When compared to standard-length humeral stem in reverse total shoulder arthroplasty (RTSA), short humeral stems in RTSA require good proximal humeral metaphyseal bone quality to gain proper and secure fixation during prosthetic implantation. Shorter humeral stems potentially carry more risk of misalignment than standard or long humeral stems. The hypothesis was that misalignment of the short humeral stems is influenced by regional bone quality. METHODS: RTSA with a short curved humeral stem with neck-shaft angle (NSA) default of 132.5° was reviewed. The study group included 35 cases at a mean age of 75.97 (± 6.23) years. Deltoid-tuberosity index (DTI) was measured to evaluate proximal humeral bone quality. The deltoid tuberosity index was measured at immediately above position of the upper end of the deltoid tuberosity. Stem alignment was given by the angle measured in degrees between the intramedullary humeral shaft axis and the axis of the humeral implant stem. RESULTS: The patient's mean DTI was 1.37 ± 0.16 (median, 1.32; range, 1.12-1.80). 22 patients had poor bone quality (DTI < 1.4), compared to 13 patients with acceptable bone quality (DTI > 1.4). After RTSA, ten humeral components (29%) were neutrally aligned, whereas 25 humeral components (71%) were misaligned. There was no correlation between misalignment and DTI (r = 0.117; p = 0.504). But there was a strong correlation between misalignment and the patient's own NSA (r = - 0.47; p = 0.004). The postoperative stem position and stem misalignment are not associated with functional outcomes (p > 0.05). CONCLUSION: The misalignment of the short curved humeral stem frequently occurs. Poor reginal humeral bone quality does not influence misalignment after RTSA with a short humeral stem. Postoperative stem alignment is associated with the patient's preoperative NSA and method of neck cut. The misalignment does not affect functional outcomes for midterm follow-up. Further long-term follow-up studies are needed to confirm its clinical relevance.

Programmed Death Ligand 1 Regulatory Crosstalk with Ubiquitination and Deubiquitination: Implications in Cancer Immunotherapy.

Programmed death ligand 1 (PD-L1) plays a pivotal role in cancer immune evasion and is a critical target for cancer immunotherapy. This review focuses on the regulation of PD-L1 through the dynamic processes of ubiquitination and deubiquitination, which are crucial for its stability and function. Here, we explored the intricate mechanisms involving various E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) that modulate PD-L1 expression in cancer cells. Specific ligases are discussed in detail, highlighting their roles in tagging PD-L1 for degradation. Furthermore, we discuss the actions of DUBs that stabilize PD-L1 by removing ubiquitin chains. The interplay of these enzymes not only dictates PD-L1 levels but also influences cancer progression and patient response to immunotherapies. Furthermore, we discuss the therapeutic implications of targeting these regulatory pathways and propose novel strategies to enhance the efficacy of PD-L1/PD-1-based therapies. Our review underscores the complexity of PD-L1 regulation and its significant impact on the tumor microenvironment and immunotherapy outcomes.

Value of postoperative computed tomography for the diagnosis of lateral hinge fracture in medial opening-wedge supramalleolar osteotomy.

INTRODUCTION: It remains unclear whether computed tomography (CT) is superior to plain radiography in detecting lateral hinge fractures after medial opening-wedge supramalleolar osteotomy (SMO) of the ankle joint. This study aimed to evaluate the disparity between postoperative plain radiography and CT in detecting lateral hinge fractures after medial opening-wedge SMO and to identify the predictive factors of lateral hinge fractures. MATERIALS AND METHODS: This retrospective study included 39 patients who underwent medial opening-wedge SMO. The immediate postoperative plain radiography and CT scan images were retrieved, and the presence of lateral hinge fractures was independently determined. Depending on the fracture gap, the lateral hinge fractures were subclassified as stable (gap < 2 mm) or unstable (gap ≥ 2 mm) fractures. To investigate the predictive factors, the cases were divided based on diagnostic tools such as plain radiography and CT. RESULTS: The incidence of lateral hinge fractures was 48.7% (19/39) on plain radiographs and 61.5% (24/39) on CT scans. Five cases of lateral hinge fractures additionally detected on CT scans were stable fractures, and all had been classified as no fracture on plain radiographs. The unstable fractures that had been subclassified based on plain radiographs did not change on CT scans. None of the variables were associated with the presence of lateral hinge fractures on plain radiographs and CT scans. CONCLUSIONS: Postoperative CT after medial opening-wedge SMO has no additional diagnostic value if the lateral hinge fracture has already been diagnosed on plain radiography. Therefore, postoperative CT is only recommended when lateral hinge fractures are not visible on plain radiographs.

Does stress shielding after radial head arthroplasty affect functional outcomes?

BACKGROUND: Various complications related to the prosthesis, such as implant loosening and stress shielding phenomenon, could develop after prosthetic replacement of the radial head. Stress shielding is known to occur around rigidly fixed implants. The purpose of this study was to evaluate the clinical influence and causative factors of the stress shielding phenomenon after radial head arthroplasty (RHA). METHODS: Clinical records and radiographs of 56 patients with unreconstructable radial head fractures who received radial head replacement between 2009 and 2019 were reviewed. Exclusion criteria were infection, loosening, and follow-up of less than 24 months. After exclusion, 35 patients were enrolled. Patients were divided into two groups: an anatomical press-fit group (Anatomical Radial Head System; Acumed, Hillsboro, OR, USA) and a round bipolar cemented group (RHS; Tornier, Montbonnot Saint-Martin, France). Stress shielding around the prosthesis was assessed in the serial radiological examination. Clinical results were assessed using Mayo elbow performance score (MEPS), Quick Disabilities of the Arm, Shoulder, and Hand (q-DASH) score, range of motion (flexion-extension arc and pronation-supination arc), and visual analog scale score (VAS). Correlations between stress shielding phenomenon and demographic data and functional results were analyzed. RESULTS: At an average follow-up of 43.06 (± 14.6) months, 14 (40%) out of 35 fixed stems demonstrated stress shielding. Our results showed that the rate of stress shielding was significantly higher in cases with a bilateral ligament injury and in the anatomical press-fit group (p = 0.028 and p = 0.0091, respectively). However, stress shielding around prostheses did not affect the clinical results (p > 0.05). CONCLUSION: The stress shielding phenomenon around radial head prosthesis may vary according to prosthetic design and severity of ligament injuries. Stress shielding does not affect the mid-term outcomes in the treatment of acute fractures of the radial head. LEVEL OF EVIDENCE III: Retrospective Cohort Comparison; Treatment Study.

Flexion-extension-supination test compared to arthroscopic findings of biceps long head pathology: A physical examination that reflect anatomical evolution of human shoulder girdle.

The accuracy of physical examination for diagnosing lesions of the long head of the biceps tendon (LHBT) remains unsatisfactory. The purpose of this study was to describe a new diagnostic test, the Flexion-Extension-Supination (FES) test for diagnosing lesions of the long head of biceps tendon. A prospective study of 162 patients was performed to evaluate the diagnostic value of FES test. All the participants were evaluated on the basis of their clinical presentation, physical examination (FES test), radiologic findings and arthroscopic examination. Shoulder arthroscopy findings were used as the gold standard. To reduce the omission of the hidden lesion, LHBT was checked at the intra- and the extraarticular side via arthroscopic examination. Surgical findings related to biceps pathology were as follows: rotator cuff tears, 89.5% (145/162); subacromial impingement, 8.6% (14/162); and biceps tendinitis, 1.9% (3/162). The prevalence of biceps pathology was 77.2% (125/162) of all arthroscopic procedures. No significant differences for LHBT lesions were observed between the FES test and the arthroscopic findings (P = .850). The interrater reliability of the FES test was 0.747. After excluding inconclusive results between examiners, the sensitivity, specificity, positive predictive value, and negative predictive value of the FES test were 87.9%, 66.7%, 82.9%, and 63.2%, respectively. Positive and negative likelihood ratios were 2.67 and 0.18, respectively. The maneuvers of the FES test irritate intra- and extraarticular lesion of LHBT. The FES test is a reproducible and reliable test that can be used during physical examinations to evaluate patients with LHBT lesions.

Nicotinamide Riboside Vitamin B3 Mitigated C26 Adenocarcinoma-Induced Cancer Cachexia.

Nicotinamide riboside (NR), vitamin B3, is a substrate for nicotinamide adenine dinucleotide (NAD+)-consuming enzymes and is a coenzyme for hydride-transfer enzymes, including adenosine diphosphate (ADP)-ribose transferases, poly (ADP-ribose) polymerases, cADP-ribose synthases, and sirtuins, which play a central role in the aging process, neurodegenerative processes, and myopathy. Since cancer cachexia is a disease condition presenting with weight loss, skeletal muscle atrophy, and loss of adipose tissue in patients with advanced cancer, we hypothesized that NR intake could ameliorate sarcopenia. In this study, we investigated whether preemptive administration of NR ameliorated C26 adenocarcinoma-induced cancer cachexia and explored anti-cachexic mechanisms focused on the changes in muscle atrophy, cachexic inflammation, and catabolic catastrophe. Dietary intake of the NR-containing pellet diet significantly attenuated cancer cachexia in a mouse model. Starting with significant inhibition of cachexic factors, tumor necrosis factor alpha, and interleukin-6, NR significantly inhibited muscle-specific ubiquitin-proteasome ligases, such as atrogin-1, muscle RING-finger protein-1 (MuRF-1), mitofusin-2, and peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PCG-1α). Significant inhibition of epididymal fat lipolysis was noted with significant inhibition of adipose triglyceride lipase (ATGL) gene. Furthermore, NR administration significantly increased the levels of crucial enzymes involved in the biosynthesis of NAD+ and nicotinamide phosphoribosyl transferase and significantly inhibited the NAD+-sensitive deacetylase sirtuin 1 (SIRT1). Preemptive intake of NR in patients vulnerable to cachexia can be a preemptive option to ameliorate cancer cachexia.

Transcriptome profiling analysis of the response to walnut polyphenol extract in Helicobacter pylori-infected cells.

Dietary intervention to prevent Helicobacter pylori (H. pylori)-associated gastric diseases seems to be ideal with no risk of bacterial resistance, safe long-term intervention, and correcting pathogenic mechanisms including rejuvenation of precancerous atrophic gastritis and anti-mutagenesis. A transcriptome as set of all RNAs transcribed by certain tissues or cells demonstrates gene functions and reveals the molecular mechanism of specific biological processes against diseases. Here, we have performed RNAseq and bioinformatic analysis to explain proof of concept that walnut intake can rescue from H. pylori infection and explore unidentified mode of actions of walnut polyphenol extract (WPE). As results, BIRC3, SLC25A4, f3 transcription, VEGFA, AZU1, HMOX1, RAB3A, RELBTNIP1, ETFB, INPP5J, PPME1, RHOB, TPI1, FOSL1, JUND.RELB, KLF2, MUC1, NDRG1, ALDOA, ENO1, PFKP, GPI, GDF15, and NRTN genes were newly discovered to be enriched with WPE, whereas CCR4, BLNK, CCR7, CXCR4, CDO1, KLSG1, SELE, RASGRP2, PIK3R3, TSPAN32, HOXC-AS3, HCG8, BTNL8, and CXCL3 genes as inhibitory targets by WPE in H. pylori infection. We identified additional genes what WPE afforded actions of avoiding H. pylori-driven onco-inflammation and rejuvenating precancerous atrophic gastritis. Conclusively, after applying RNAseq analysis in order to document walnut intake for precision medicine against H. pylori infection, significant transcriptomic profiling applicable for validation were drawn.

Vertical Interfragmentary Doubled Suture for Displaced Patella Fractures: Sequential Compressive Tightening with Nice Knot.

In the treatment of displaced patella fractures, open reduction and internal fixation is essential for patellofemoral congruency and restoration of the knee extension mechanism. Various surgical techniques and materials can be used, and their clinical outcomes are favorable. However, soft-tissue and skin irritation, pain, and limited range of motion due to metallic hardware can occur, and removal of hardware such as screws and K-wire may be required after bony union. We present a vertical interfragmentary suture technique for patella fractures using sequential compressive tightening with the Nice knot. This knot-tying technique is low profile, provides stable fixation enough to hold displaced fractures, and does not require a secondary procedure for hardware removal.

Dietary walnut as food factor to rescue from NSAID-induced gastrointestinal mucosal damages.

Nuclear factor erythroid-derived 2-like 2 (Nrf-2) is transcription factor implicated in the antioxidant response element-mediated induction of endogenous antioxidant enzyme such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase, and NAD(P)H quinone dehydrogenase 1, among which HO-1 is an enzyme catalyzing the degradation of heme.producing biliverdin, ferrous iron, and carbon monoxide. In the stomach, as much as regulating gastric acid secretions, well-coordinated establishment of defense system stands for maintaining gastric integrity. In previous study, author et al. for the first time discovered HO-1 induction was critical in affording faithful gastric defense against various irritants including Helicobacter pylori infection, stress, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and toxic bile acids. In this review article, we can add the novel evidence that dietary walnut intake can be reliable way to rescue from NSAIDs-induced gastrointestinal damages via the induction of HO-1 transcribed with Nrf-2 through specific inactivation of Keap-1. From molecular exploration to translational animal model of indomethacin-induced gastrointestinal damages, significant induction of HO-1 contributed to rescuing from damages. In addition to HO-1 induction action relevant to walnut, we added the description the general actions of walnut extracts or dietary intake of walnut regarding cytoprotection and why we have focused on to NSAID damages.

Associations between age and dyslipidemia are differed by education level: The Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) cohort.

BACKGROUND: Dyslipidemia is a multifactorial disorder, which arises from complex interactions among genetic and environmental risk factors. Previous studies have established the deteriorating effect of aging on lipid profiles. However, little is known about the role of education level, a stable marker of socioeconomic status, which reflect modifiability of lifestyle risk factors. Therefore, we examined the association between age and individual dyslipidemia parameter across education level among healthy, middle-aged Korean women. METHODS: From 2049 middle-aged women, education attainment was classified into completion of elementary school or below, middle school, high school, college or above. Dyslipidemia was assessed in adherence to the 2018 Korean Dyslipidemia Treatment Guideline. Multivariable logistic regression and generalized linear model tested for associations between age and dyslipidemia parameter across education level and other known risk factors, including menopause, obesity, and current drinking and smoking. RESULTS: In this cross-sectional analysis, the prevalence of each dyslipidemia parameter was significantly different by age and education level. The odds ratio (OR) for dyslipidemia was higher among participants who were older and had received higher education (OR = 2.31, p for interaction = 0.008) than younger and low education counterpart. The interaction between age and education level remained significant for hypercholesterolemia (p for interaction = 0.003) and hyper-LDL-cholesterolemia (p for interaction = 0.002). CONCLUSIONS: Separate examination of individual dyslipidemia parameter indicated varying degree of interaction with age and education level. Such results imply that each type of lipid abnormality may arise from and be exacerbated by heterogeneous composition of biological and lifestyle risk factors, which may be reflected by education level.

Recent Advances in the Development of TGF-ß Signaling Inhibitors for Anticancer Therapy.

TGF-ß is a multifunctional cytokine that plays an important role in both physiologic and pathologic processes, including cancer. Importantly, TGF-ß has a dual role in tumorigenesis, acting as a tumor suppressor or a tumor promoter, depending on the stage of tumor development. The aberrantly upregulated production of TGF-ß has been strongly implicated in tumor progression, angiogenesis, and metastasis, as well as immune evasion. Therefore, hyperactivated TGF-ß signaling is considered a potential therapeutic target for cancer therapy. Numerous inhibitors of overactivated TGF-ß signaling have been developed, and some of them are currently in clinical trials. This review focuses on the TGF-ß signaling that contributes to tumor progression and immune evasion in the tumor microenvironment and presents recent achievements on TGF-ß signaling inhibition as a single or combined therapeutic approach in cancer therapy.

Role of omega-3 polyunsaturated fatty acids in preventing gastrointestinal cancers: current status and future perspectives.

INTRODUCTION: Although inflammation is defensive and healing process that maintains organ homeostasis, unresolved inflammation can lead to diseases. Polyunsaturated fatty acids (PUFAs), especially n-6 PUFAs abundant in Western diet, are precursors of pro-inflammatory mediators, whereas n-3 PUFAs possess anti-inflammatory properties. Therefore, interest in the cancer-preventive effect of n-3 PUFAs is increasing. Areas covered: We have observed significant reductions of gastrointestinal tumorigenesis in the Fat-1 transgenic mouse as evidenced that the decrease in Helicobacter pylori-infected gastric tumorigenesis, colon, biliary, and pancreatic cancer was seen in Fat-1 mice producing n-3 PUFAs. However, despite many studies showing benefits, evidence-based medicine regarding molecular pathology, epidemiology, and clinical achievement of cancer prevention of n-3 PUFAs are still limited. Expert commentary: Primary deficiency of eicosapentaenoic acids and docosahexaenoic acids in Western diets can explain the risk of cancer development and the importance of n-3/n-6 PUFA ratio in reducing cancer risk. Alteration of cell membrane composition during carcinogenesis is particularly important, due to increased rate of lipid/cholesterol synthesis in cancerous tissues. Here, we discuss that direct incorporation of n-3 PUFAs in the cell membrane corrects abnormal cellular proliferation and decreases inflammation-associated carcinogenesis. This is exemplified by cancer-preventive effects of n-3 PUFAs as fat sources for gastrointestinal cancers.

Supplementary Technique for Unstable Clavicle Shaft Fractures: Interfragmentary Wiring and Temporary Axial K-Wire Pinning.

BACKGROUND: Treatment of unstable clavicle fractures remains a challenge for orthopedic surgeons, but the evolution of treatment strategies has allowed for reliable results with minimal complications. Although several surgical options exist, open reduction with plating remains the treatment of choice for clavicle fractures. The purpose of this study is to determine an easy way to achieve successful preplating reduction while minimizing surrounding soft tissue damage during treatment of midshaft fractures of the clavicle. METHODS: A retrospective study included all consecutive adult patients operated on by a single surgeon for acute displaced clavicular midshaft fracture between January 2010 and October 2014. Hybrid technique with interfragmentary cerclage wiring, temporary axial K-wire pinning, or their combination was used in all patients. The demographic data and clinical outcomes, including operation time, union time, restoration of anatomy, shoulder functional score, and complications were evaluated. RESULTS: There were 54 male and 19 female patients, with an average age of 39.3 years (range, 18 to 77 years) for males and 58.3 years (range, 39 to 77 years) for females. They were followed up for 24 months (range, 12 to 44 months). All patients had reliable bone union after surgery using interfragmentary cerclage wiring and temporary axial K-wire fixation; fracture union was obtained at an average of 11.7 weeks (range, 8 to 21 weeks) postoperatively. Additionally, there was no postoperative loss of fracture reduction or plate loosening. At the final follow-up, all patients had regained excellent functional outcomes. CONCLUSIONS: The cognizant effort to achieve anatomic reduction without surrounding soft tissue insult before definitive plating allows excellent radiologic and functional outcomes. Interfragmentary cerclage wiring and temporary axial K-wire pinning can overcome difficulties associated with unstable clavicle fractures to allow proper fracture reduction. In this article, we introduce a concise technique for achieving the desired outcomes reliably and efficiently when treating unstable clavicle midshaft fractures.

The Role of Tripartite Motif Family Proteins in TGF-ß Signaling Pathway and Cancer.

TGF-ß signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The TGF-ß signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of TGF-ß signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the TGF-ß signaling pathway with relevance to cancer.

Primary exploration for radial nerve palsy associated with unstable closed humeral shaft fracture.

BACKGROUND: The treatment of radial nerve palsy caused by closed humeral shaft fracture is a matter of debate. The purpose of this study is to evaluate the outcome of early surgical management of radial nerve palsy in patients with unstable closed humeral shaft fractures and to determine whether patients with this injury should be surgically explored. METHODS: Medical records of 15 consecutive patients who had undergone open reduction and internal fixation for unstable closed humeral shaft fractures were reviewed. Injury mechanisms, radiographs, intraoperative findings of the injured nerve, and clinical improvement were analyzed. Of the 15 patients, two were injured during simple falls, two during baseball pitching, one by a fall from a height, one during skiing, and one by direct machine impaction during work. Fracture locations were middle humerus in six patients, middle-distal in eight patients, and middle-proximal in one patient. Fracture patterns were transverse fracture in six patients, butterfly segment fracture in four patients, oblique segment fracture in three patients, and spiral fracture in two patients. RESULTS: Eleven patients showed macroscopically intact nerves, and four had total nerve transection. All four patients with total nerve transection were injured in traffic accident. Of these four patients, one showed comminuted fracture with butterfly fragment on the middle-distal shaft and the other three showed displaced transverse fracture on the middle to middle-distal shaft area. Transected nerves were directly repaired in two patients. In the other two patients, humerus shortening and nerve grafting were performed because of mangled nerve endings. All patients who had intact nerves showed fully recovered function at the last follow-up. CONCLUSION: For radial nerve palsy accompanied by unstable humeral shaft fracture, primary exploration of the radial nerve and open reduction and plate fixation of the fracture should be considered as a treatment of choice. High-energy trauma, fracture location at the middle-distal humerus, and simple transverse fracture or comminuted fracture with butterfly fragment seems to be risk factors for radial nerve transection.

Targeted molecular ablation of cancer stem cells for curing gastrointestinal cancers.

INTRODUCTION: Abundance of the ATPase-binding cassette (ABC) transporters and deranged self-renewal pathways characterize the presence of cancer stem cells (CSCs) in gastrointestinal cancers (GI cancers), which play crucial roles in tumorigenesis, chemotherapy resistance, tumor recurrence, and cancer metastasis. Therefore, in order to ensure high cure rates, chemoquiescence, CSCs should be ablated. Recent advances in either understanding CSCs or biomarker identification enable scientists to develop techniques for ablating CSCs and clinicians to provide cancer cure, especially in GI cancers characterized by inflammation-driven carcinogenesis. Areas covered: A novel approach to ablate CSCs in GI cancers, including esophageal, gastric, and colon cancers, is introduced along with explored underlying molecular mechanisms. Expert commentary: Though CSC ablation is still in the empirical stages and not in clinical practice, several strategies for ablating CSCs in GI cancers had been published, proton-pump inhibitors (PPIs) that regulate the membrane-bound ABC transporters, which underlie drug resistance; chloroquine (CQ) that inhibits autophagy, which is responsible for tumor survival; Hedgehog/Wnt/Notch inhibitors that influence the underlying stem-cell growth, and some natural products including Korean red ginseng, cancer-preventive kimchi, Artemisia extract, EGCG from green tea, and walnut extracts.

Emerging Targets to Relieve Fat Stress-Induced Liver Diseases: UDCA, Tocotrienol, ω-3 PUFAs, and IgY Targeted NPC1L1 Cholesterol Transporter.

Fat stress-induced liver disease is a hepatic manifestation of metabolic syndrome initiated by excess fat accumulation and encompasses a wide spectrum of diseases from non-alcoholic fatty liver disease to nonalcoholic steatohepatitis, a precursor lesion progressing to more aggressive liver cirrhosis and hepatocellular carcinoma. Although the incidence of these fat stress-induced liver diseases is rapidly increasing worldwide in parallel with the growing epidemics of obesity and metabolic diseases, its exact pathogenesis is not well defined. Although obesity, sedentary life-style, altered dietary pattern, insulin resistance, altered intestinal barrier function, inflammatory cytokines, and oxidative stress have been acknowledged as contributing factors because of the indefinite pathogenesis of metabolic diseases, the only reliable treatment is lifestyle intervention composed of restrictive diet and exercise. Additionally, some existing medications such as pioglitazone and antioxidants such as vitamin E were reported to be effective; in this review, several novel agents especifically targeting nonalcoholic fatty liver disease pathogenesis under clinical trial will be introduced. These include an NPC1L1 blocker (ezetimibe), which significantly improved histological and symptomatic scores associated with steatohepatitis and fibrosis; clofibrate, phentoxyfylline, ursodeoxycholic acid, and tocopherol, all of which are prescribed to relieve fat stress; and additional IgY targeted NPC1L1, tocotrienol, ursodeoxycholic acid, and ω-3 polyunsaturated fatty acids, which are actively under investigation to confirm the safety of long-term use.

[Role of Inhibitory Transforming Growth Factor-ß Signal Smad7 in Helicobacter pylori-associated Gastric Damage].

BACKGROUND/AIMS: Transforming growth factor-beta (TGF-ß) is a cytokine implicated in the susceptibility, development, and progression of gastrointestinal cancer and certain other neoplasms. In the later stages of cancer, TGF-ß not only acts as a bystander of host-immune response, but also contributes to cell growth, invasion, and metastasis. In the current study, we generated gastric mucosal cells that stably express Smad7, and explored the Helicobacter pylori-associated biological changes between mock-transfected and Smad7-transfected RGM1 cells. METHODS: RGM1 cells stably transfected with Smad7 were infected with H. pylori, and molecular changes in apoptotic markers and inflammatory mediators were examined. Several candidate genes were explored in Smad7-overexpressing cells after H. pylori infection. RESULTS: Overexpression of Smad7 in RGM1 cells significantly increased the H. pylori-induced cytotoxicity compared to mock-transfected cells. Exaggerated increases in inflammatory mediators, cyclooxygenase 2, inducible NO synthase, and augmented apoptosis were noted in Smad7-overexpressing cells, whereas mitigated heme oxygenase 1 was noted in Smad7- overexpressing cells. These phenomena were reversed in cells transfected with Smad7 siRNA. CONCLUSIONS: These data suggest that inhibition of Smad7 is a possible target for mitigating H. pylori-associated inflammation.

Hepatic Elovl6 gene expression is regulated by the synergistic action of ChREBP and SREBP-1c.

Elongation of very long chain fatty acids protein 6 (ELOVL6), a rate-limiting enzyme for the elongation of saturated and monounsaturated fatty acids with 12, 14, and 16 carbons, plays a key role in energy metabolism and insulin sensitivity. Hepatic Elovl6 expression is upregulated in the fasting-refeeding response and in leptin-deficient ob/ob mice. Mouse Elovl6 has been shown to be a direct target of sterol regulatory element binding protein-1 (SREBP-1) in response to insulin. In the present study, we demonstrated that mouse and human Elovl6 expression is under the direct transcriptional control of carbohydrate response element binding protein (ChREBP), a mediator of glucose-induced gene expression. Serial deletion and site-directed mutagenesis studies revealed functional carbohydrate response elements (ChoREs) in the mouse and human Elovl6 promoters and gel shift assays and chromatin immunoprecipitation assays confirmed the binding of ChREBP to the Elovl6-ChoRE sites. In addition, the ectopic co-expression of ChREBP and SREBP-1c in HepG2 cells synergistically stimulated Elovl6 promoter activity and this synergistic activation was abolished by mutating the Elovl6 promoter ChoREs. Taken together, these results suggest that the synergistic action of ChREBP and SREBP-1c is necessary for the maximal induction of Elovl6 expression in the liver.

Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B.

In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved.