C-terminally mutated tubby protein accumulates in aggresomes

The tubby protein (Tub), a putative transcription factor, plays important roles in the maintenance and function of neuronal cells. A splicing defect-causing mutation in the 3'-end of the tubby gene, which is predicted to disrupt the carboxy-terminal region of the Tub protein, causes maturity-onset obesity, blindness, and deafness in mice. Although this pathological Tub mutation leads to a loss of function, the precise mechanism has not yet been investigated. Here, we found that the mutant Tub proteins were mostly localized to puncta found in the perinuclear region and that the C-terminus was important for its solubility. Immunocytochemical analysis revealed that puncta of mutant Tub co-localized with the aggresome. Moreover, whereas wild-type Tub was translocated to the nucleus by extracellular signaling, the mutant forms failed to undergo such translocation. Taken together, our results suggest that the malfunctions of the Tub mutant are caused by its misfolding and subsequent localization to aggresomes.ope

Multiple roles of phosphoinositide-specific phospholipase C isozymes

Phosphoinositide-specific phospholipase C is an effector molecule in the signal transduction process. It generates two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. Currently, thirteen mammal PLC isozymes have been identified, and they are divided into six groups: PLC-beta, -gamma, -delta, -epsilon, -zeta and -eta. Sequence analysis studies demonstrated that each isozyme has more than one alternative splicing variant. PLC isozymes contain the X and Y domains that are responsible for catalytic activity. Several other domains including the PH domain, the C2 domain and EF hand motifs are involved in various biological functions of PLC isozymes as signaling proteins. The distribution of PLC isozymes is tissue and organ specific. Recent studies on isolated cells and knockout mice depleted of PLC isozymes have revealed their distinct phenotypes. Given the specificity in distribution and cellular localization, it is clear that each PLC isozyme bears a unique function in the modulation of physiological responses. In this review, we discuss the structural organization, enzymatic properties and molecular diversity of PLC splicing variants and study functional and physiological roles of each isozyme.open19320

Macrolide-refractory Mycoplasma pneumoniae pneumonia and hemophagocytic lymphohistiocytosis: case report and literature review

Mycoplasma pneumoniae causes various extra-pulmonary complications. As a rare but fatal hematological complication, hemophagocytic lymphohistiocytosis (HLH) can be observed in children with M. pneumoniae infection. We report a case of a 6-year-old girl with HLH who was initially presumed to have macrolide-refractory M. pneumoniae pneumonia. Despite the combination treatment of antimicrobial and anti-inflammatory agents, she showed persistent fever, hepatosplenomegaly, and thrombocytopenia. Secondary HLH associated with M. pneumoniae should be considered if unexplained clinical deterioration is noted in children with macrolide-refractory M. pneumoniae pneumonia

Effect of Agrimonia pilosa Ledeb Extract on the Antinociception and Mechanisms in Mouse

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 µg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (α2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by α2-adrenergic receptor, but not opioidergic and serotonergic receptors

Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia

IntroductionL-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN.MethodsThe study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias.ResultsThe analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17–1.62) or the complete response rate (OR 0.86; 95% CI = 0.29–2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36–2.78 and OR 1.24; 95% CI, 0.50–3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups.ConclusionThere is no clear rationale for avoiding Asp-TPN in ASNase-treated patients

Comparison of Surgical Burden, Radiographic and Clinical Outcomes According to the Severity of Baseline Sagittal Imbalance in Adult Spinal Deformity Patients

Objective To determine the clinical impact of the baseline sagittal imbalance severity in patients with adult spinal deformity (ASD). Methods We retrospectively reviewed patients who underwent ≥ 5-level fusion including the pelvis, for ASD with a ≥ 2-year follow-up. Using the Scoliosis Research Society-Schwab classification system, patients were classified into 3 groups according to the severity of the preoperative sagittal imbalance: mild, moderate, and severe. Postoperative clinical and radiographic results were compared among the 3 groups. Results A total of 259 patients were finally included. There were 42, 62, and 155 patients in the mild, moderate, and severe groups, respectively. The perioperative surgical burden was greatest in the severe group. Postoperatively, this group also showed the largest pelvic incidence minus lumbar lordosis mismatch, suggesting a tendency towards undercorrection. No statistically significant differences were observed in proximal junctional kyphosis, proximal junctional failure, or rod fractures among the groups. Visual analogue scale for back pain and Scoliosis Research Society-22 scores were similar across groups. However, severe group’s last follow-up Oswestry Disability Index (ODI) scores significantly lower than those of the severe group. Conclusion Patients with severe sagittal imbalance were treated with more invasive surgical methods along with increased the perioperative surgical burden. All patients exhibited significant radiological and clinical improvements after surgery. However, regarding ODI, the severe group demonstrated slightly worse clinical outcomes than the other groups, probably due to relatively higher proportion of undercorrection. Therefore, more rigorous correction is necessary to achieve optimal sagittal alignment specifically in patients with severe baseline sagittal imbalance

Compositional assessment of carotenoid-biofortified rice using substantial equivalence

One important aspect in assessing the safety of genetically modified (GM) crops for human consumption is characterizing their nutrient composition. A β-carotene-biofortified rice was generated by inserting phytoene synthase (Psy) and carotene desaturase (Crtl) genes isolated from Capsicum and Pantoea into the genome of a conventional variety of rice (Nakdongbyeo). Nutrients (proximates, amino acids, fatty acids, minerals, and vitamins), anti-nutritive components (trypsin inhibitors and phytic acid), and ferulic acid in GM rice were compared with those in the parent line Nakdongbyeo. Statistical comparisons to test for equivalence showed that all of the analyzed components in the GM plants were equivalent to those in its non-transgenic counterpart, and most nutritional components fell within the range of values reported for other commercial lines, indicating the safety of the GM plant.Key words: Genetically modified crop, β-Carotene, Transgenic rice, Nutrient, Substantial equivalence

Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn

We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor

Lung function, coronary artery calcification, and metabolic syndrome in 4905 Korean males

SummaryBackgroundImpaired lung function is an independent predictor of cardiovascular mortality. We assessed the relationships of lung function with insulin resistance (IR), metabolic syndrome (MetS), systemic inflammation and coronary artery calcification score (CACS) measured by computed tomography (CT) scan an indicator of coronary atherosclerosis.MethodsWe identified 4905 adult male patients of the Health Promotion Center in Samsung Medical Center between March 2005 and February 2008 and retrospectively reviewed the following data for these patients: pulmonary function, CT-measured CACS, anthropometric measurement, fasting glucose, insulin, lipid profiles, serum C-reactive protein (CRP) and homeostatic model assessment (HOMA-IR). MetS was defined according to the AHA/NHLBI criteria.ResultsWhen the subjects were divided into four groups according to quartiles of FVC or FEV1 (% pred), serum CRP level, HOMA-IR, prevalence of MetS and CACS significantly increased as the FVC or FEV1 (% pred) decreased. The odds ratios (ORs) for MetS in the lowest quartiles of FVC and FEV1 (% pred) were 1.85 (95% CI, 1.49–2.30; p<0.001) and 1.47 (95% CI, 1.20–1.81; p<0.001) respectively. The ORs for the presence of coronary artery calcification in the lowest quartiles of FVC and FEV1 (% pred) were 1.31 (95% CI, 1.09–1.58; p=0.004) and 1.22 (95% CI, 1.02–1.46; p=0.029) respectively. Obesity, CRP, HOMA-IR, and the presence of coronary artery calcium were independent risk predictors for impaired lung function.ConclusionMetabolic syndrome, insulin resistance, coronary atherosclerosis, and systemic inflammation are closely related to the impaired lung function