SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV).Results:In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.     

Lead-Free BiFeO3-Based Piezoelectrics: A Review of Controversial Issues and Current Research State

Lead-free electroceramics represent an emerging area of research that has the potential to enable new green advances in electronics. Research has mainly focused on the development of new piezoelectric materials for replacing lead containing oxides exhibiting superior electromechanical behavior. Lead-free BiFeO₃-based materials are not only the promising candidates to replace lead-based materials but also show intriguing properties which may inspire innovative material design for the next generation of lead-free piezoceramics. This review aims to highlight the current state of research and overlooked aspects in lead-free BiFeO₃-based ceramics, which could be insightful in elucidating certain controversial issues. Current strategies to reduce high conductivity, influence of chemical heterogeneity on both functional properties and crystal structure, effective heat treatment procedures, and the role of pseudo-cubic structures on the enhancement of piezoelectric properties are subjects of highlighted within this review as they have a significant impact on the quality of BiFeO₃-based lead-free piezoelectrics (but are often disregarded).     

Spontaneous reduction of transvaginal small bowel evisceration after abdominal hysterectomy for cervical cancer: A case report

Rationale:Transvaginal evisceration of the small bowel is an extremely rare condition after hysterectomy, which requires urgent surgical intervention to prevent serious bowel morbidity and mortality.Patient concerns:A 65-year-old woman presented with sudden-onset severe abdominal pain and a mass protruding through the vagina. The past surgical history was significant, with an abdominal hysterectomy for cervical cancer performed 11 weeks prior to presentation.Diagnosis:Pelvic examination revealed prolapsed small-bowel loops (18-20 cm in length). Pelvic computed tomography scan confirmed the presence of transvaginal evisceration of the small bowel.Interventions:Bowel reduction and urgent laparotomy were the selected treatment approaches for a detailed inspection and thorough washing of the intrα-abdominal cavity. A Foley catheter was inserted in the emergency room, with the subject in the lithotomy position. The prolapsed bowel loops spontaneously reduced without manual reduction, and the vault defect was repaired transvaginally.Outcomes:The patient experienced no postoperative complications and remained disease-free for 9months postoperatively.Lessons:Transvaginal evisceration of the small bowel should be considered a surgical emergency. A multidisciplinary approach to prompt case management involving clinicians in gynecology, general surgery, and emergency medicine is vital for preventing serious consequences. Hysterectomy is the most frequently performed gynecological surgical procedure, and evisceration occurs most often after hysterectomy. Therefore, patients should be informed about this rare but possible hysterectomy complication.     

Clinical Impact of Empirical Antibiotic Therapy in Patients With Coronavirus Disease 2019 Requiring Oxygen Therapy

Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically. However, the prognostic impact of empirical antibiotic therapy has not been evaluated. We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.     

Phloroglucinol (PG) purified from Ecklonia cava attenuates radiation-induced apoptosis in blood lymphocytes and splenocytes

Phloroglucinol (PG), a polyphenol compound of Eckloniacava known as brown algae abundant in Jeju island, has been proposed to exert the antioxidative and cytoprotective effects against oxidative stress. In this study, we confirmed that PG protected mice from damages caused by ionizing radiation and investigated its protection mechanism in detail. The result showed that PG increased the viability of splenocytes without cytotoxicity. Also, PG significantly enhanced the proliferation of splenocytes by limiting the increment of sub-G₁ DNA contents via the inhibition of reactive oxygen species production in 2 Gy-irradiated splenocytes. In addition, PG significantly decreased DNA damage and the number of apoptotic fragments in lymphocytes against oxidative stress. Also, PG increased the counts of endogenous spleen CFUs, compared with only ionizing radiation-irradiated mice. These results demonstrate the multi-faceted protection mechanisms of PG in mice against oxidative stress caused by ionizing radiation, providing the benefit of inhibiting apoptosis and strengthening hematopoiesis.     

Brassinin Induces Apoptosis in PC‐3 Human Prostate Cancer Cells through the Suppression of PI3K/Akt/mTOR/S6K1 Signaling Cascades

The oncogenic PI3K/Akt/mammalian target of rapamycin (mTOR) signaling axis and its downstream effector, the ribosomal protein S6 kinase 1 (S6K1) play a key role in mediating cell survival in various tumor cells. Here, we investigated the effects of brassinin (BSN), a phytoalexin first identified as a constituent of cabbage, on the PI3K/Akt/mTOR/S6K1 activation, cellular proliferation, and apoptosis in PC‐3 human prostate cancer. BSN exerted a significant dose‐dependent cytotoxicity and reduced constitutive phosphorylation of Akt against androgen‐independent PC‐3 cells as compared to androgen‐dependent LNCaP cells. Moreover, knockdown of androgen receptor (AR) by small interfering RNA enhanced the potential effect of BSN on induction of apoptosis in LNCaP cells. BSN clearly suppressed the constitutive activation of PI3K/Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, TUNEL staining, loss of mitochondrial membrane potential, down‐regulation of antiapoptotic and proliferative proteins, activation of caspase‐3, and cleavage of PARP. Additionally, BSN could block broad‐spectrum inhibition of PI3K/Akt/mTOR/S6K1 axes, and aberrant Akt activation by pcDNA3‐myr‐HA‐Akt1 plasmid could not prevent the observed suppressive effect of BSN on constitutive mTOR activation. Finally, overexpression of Bcl‐2 also attenuated BSN‐mediated apoptosis in PC‐3 cells. Taken together, our findings suggest that BSN can interfere with multiple signaling cascades involved in tumorigenesis and might be provided as a potential therapeutic candidate for both the prevention and treatment of prostate cancer. Copyright © 2013 John Wiley & Sons, Ltd.