A comparative study of the efficacy of NAXOZOL compared to celecoxib in patients with osteoarthritis.

OBJECTIVE: Selective cyclooxygenase-2 inhibitors (celecoxib) can minimize the gastrointestinal complications related to non-steroidal anti-inflammatory drug (NSAID) use. NAXOZOL is a new combination formulation designed to provide sequential delivery of a non-enteric-coated, immediate-release esomeprazole strontium tetrahydrate 20 mg mantle followed by an enteric-coated naproxen 500 mg core. However, there have been no studies comparing NAXOZOL to celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis. This study was undertaken to compare the effects of NAXOZOL and celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis. METHODS: The randomized enrolled patients were divided into two treatment groups: a NAXOZOL group and a celecoxib group. All participants received treatments (NAXOZOL, 500/20 mg (naproxen 500 mg, esomeprazole strontium tetrahydrate 20 mg) twice per day versus celecoxib, 200 mg daily) on a 1:1 allocation basis for 12 weeks. The primary outcome was the Leeds Dyspepsia Questionnaire (LDQ) score used for non-inferiority testing. Secondary outcome measures included the Gastrointestinal Symptom Rating Scale (GSRS) score, Visual Analogue Scale (VAS) score, European Quality of Life-5 dimensions (EQ-5D) scale and the EQ-5D Visual Analogue Scale (EQ VAS). Other outcome measures included the use of supplementary or rescue drugs, and the incidence of adverse events. RESULTS: The baseline-adjusted LDQ scores immediately after 12 weeks of treatment in NAXOZOL group were not inferior to those in celecoxib group. The overall change in the baseline-adjusted GSRS score, VAS score, EQ-5D, and EQ VAS was not different between the two groups. The usage of supplementary drugs and the drug-related incidence of adverse events were not different. However, the days to use rescue drug were longer in celecoxib group than in NAXOZOL group. CONCLUSION: NAXOZOL was not inferior to celecoxib in protecting the gastrointestinal tract and providing pain relief in patients with osteoarthritis.

KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), one of the most common maternally inherited mitochondrial diseases, is caused by mitochondrial DNA mutations that lead to mitochondrial dysfunction. Several treatment options exist, including supplementation with CoQ10, vitamins, and nutrients, but no treatment with proven efficacy is currently available. In this study, we investigated the effects of a novel NAD+ modulator, KL1333, in human fibroblasts derived from a human patient with MELAS. KL1333 is an orally available, small organic molecule that reacts with NAD(P)H:quinone oxidoreductase 1 (NQO1) as a substrate, resulting in increases in intracellular NAD+ levels via NADH oxidation. To elucidate the mechanism of action of KL1333, we used C2C12 myoblasts, L6 myoblasts, and MELAS fibroblasts. Elevated NAD+ levels induced by KL1333 triggered the activation of SIRT1 and AMPK, and subsequently activated PGC-1α in these cells. In MELAS fibroblasts, KL1333 increased ATP levels and decreased lactate and ROS levels, which are often dysregulated in this disease. In addition, mitochondrial functional analyses revealed that KL1333 increased mitochondrial mass, membrane potential, and oxidative capacity. These results indicate that KL1333 improves mitochondrial biogenesis and function, and thus represents a promising therapeutic agent for the treatment of MELAS.

Depression in breast cancer patients who have undergone mastectomy: A national cohort study.

OBJECTIVE: The objective of this study was to compare the incidence of post-operative depression in breast cancer patients who have undergone mastectomy with the incidence of post-operative depression in non-breast cancer participants (controls). METHODS: Using data from the Korean Health Insurance Review and Assessment Service (HIRA), we selected 2,130 patients with breast cancer who have undergone mastectomy for this national cohort study and matched these patients 1:4 with 8,520 control participants according to age, sex, income, region, and pre-operative depression. The incidence of post-operative depression was measured from mastectomy year to post-op year 10. The Mann-Whitney U test was used for data analysis, and the false-discovery rate was applied to determine statistical significance (P < 0.05). RESULTS: The incidence of depression was higher in the breast cancer with mastectomy group than in the control group up to 3 years after mastectomy). However, there was no difference in the incidence of depression between the breast cancer with mastectomy group and the control group after post-op 4 years. The incidence of depression was higher in the breast cancer with mastectomy group than in the control group up to 2 years after mastectomy, and there was no difference in the incidence of depression between the two groups after post-op 3 years in middle-aged and older adults (≥ 40 years old). In young adults (≤ 39 years old), the incidence of depression was significantly higher in the breast cancer with mastectomy group than in the control group in mastectomy year. CONCLUSION: Patients undergoing mastectomy for breast cancer experience depression more frequently than healthy people. However, patients overcome their depressive mood symptoms during the postoperative period. Young adults overcome their symptoms more quickly than middle-aged and older adults.

Beta-lapachone, a modulator of NAD metabolism, prevents health declines in aged mice.

NADH-quinone oxidoreductase 1 (NQO1) modulates cellular NAD(+)/NADH ratio which has been associated with the aging and anti-aging mechanisms of calorie restriction (CR). Here, we demonstrate that the facilitation of NQO1 activity by feeding ß-lapachone (ßL), an exogenous NQO1 co-substrate, prevented age-dependent decline of motor and cognitive function in aged mice. ßL-fed mice did not alter their food-intake or locomotor activity but did increase their energy expenditure as measured by oxygen consumption and heat generation. Mitochondrial structure and numbers were disorganized and decreased in the muscles of control diet group but those defects were less severe in ßL-fed aged mice. Furthermore, for a subset of genes associated with energy metabolism, mice fed the ßL-diet showed similar changes in gene expression to the CR group (fed 70% of the control diet). These results support the potentiation of NQO1 activity by a ßL diet and could be an option for preventing age-related decline of muscle and brain functions.