Boron Stress Activates the General Amino Acid Control Mechanism and Inhibits Protein Synthesis

Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS) of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance

Lithium promotes long-term neurological recovery after spinal cord injury in mice by enhancing neuronal survival, gray and white matter remodeling, and long-distance axonal regeneration

Spinal cord injury (SCI) induces neurological deficits associated with long-term functional impairments. Since the current treatments remain ineffective, novel therapeutic options are needed. Besides its effect on bipolar mood disorder, lithium was reported to have neuroprotective activity in different neurodegenerative conditions, including SCI. In SCI, the effects of lithium on long-term neurological recovery and neuroplasticity have not been assessed. We herein investigated the effects of intraperitoneally administered lithium chloride (LiCl) on motor coordination recovery, electromyography (EMG) responses, histopathological injury and remodeling, and axonal plasticity in mice exposed to spinal cord transection. At a dose of 0.2, but not 2.0 mmol/kg, LiCl enhanced motor coordination and locomotor activity starting at 28 days post-injury (dpi), as assessed by a set of behavioral tests. Following electrical stimulation proximal to the hemitransection, LiCl at 0.2 mmol/kg decreased the latency and increased the amplitude of EMG responses in the denervated hindlimb at 56 dpi. Functional recovery was associated with reduced gray and white matter atrophy rostral and caudal to the hemitransection, increased neuronal survival and reduced astrogliosis in the dorsal and ventral horns caudal to the hemitransection, and increased regeneration of long-distance axons proximal and distal to the lesion site in mice receiving 0.2 mmol/kg, but not 2 mmol/kg LiCl, as assessed by histochemical and immunohistochemical studies combined with anterograde tract tracing. Our results indicate that LiCl induces long-term neurological recovery and neuroplasticity following SCI.TUBA ; Istanbul Medipol University ; Turkish Academy of Science

SPAD GREENNESS TO ESTIMATE GENOTYPIC VARIATION IN FLAG LEAF CHLOROPHYLL IN SPRING WHEAT UNDER MEDITERRANEAN CONDITIONS

Leaf chlorophyll (Chl) is emphasized as an indicator for photosynthesis in wheat (Triticum aestivum L.). SPAD greenness meters are used to predict extractable Chl, but few studies have evaluated relationships between flag leaf greenness and Chl among wheat genotypes. Sixteen spring wheat genotypes with similar development patterns were studied in eight environments (2 years, 2 irrigation treatments and 2 sowing times) to investigate the precision of the SPAD-502 meter to predict Chl content/concentration. Relationships of Chl with SPAD greenness generally best fit linear and quadratic models. Relationships of SPAD greenness with Chl concentration were weak and inconsistent. Strongest associations were observed with Chla content (highest R2= 0.71 under late sowing), whereas associations with Chlb content were weak (highest R2 = 0.46) or insignificant. Relationships between SPAD greenness and total Chl content ranged from low (R2 = 0.24, p = 0.054) to moderate (R2 = 0.64, p < 0.001) under rainfed conventional-sowing and late-sowing conditions in the second year, respectively. SPAD greenness can be used to diagnose spring wheat genotypes differing in flag leaf Chla and total Chl content under warm Mediterranean conditions, but may not always applicable in cooler Mediterranean conditions, where genetic variability, especially in Chlb, was not expressed adequatelyLeaf chlorophyll (Chl) is emphasized as an indicator for photosynthesis in wheat (Triticum aestivum L.). SPAD greenness meters are used to predict extractable Chl, but few studies have evaluated relationships between flag leaf greenness and Chl among wheat genotypes. Sixteen spring wheat genotypes with similar development patterns were studied in eight environments (2 years, 2 irrigation treatments and 2 sowing times) to investigate the precision of the SPAD-502 meter to predict Chl content/concentration. Relationships of Chl with SPAD greenness generally best fit linear and quadratic models. Relationships of SPAD greenness with Chl concentration were weak and inconsistent. Strongest associations were observed with Chla content (highest R2= 0.71 under late sowing), whereas associations with Chlb content were weak (highest R2 = 0.46) or insignificant. Relationships between SPAD greenness and total Chl content ranged from low (R2 = 0.24, p = 0.054) to moderate (R2 = 0.64, p < 0.001) under rainfed conventional-sowing and late-sowing conditions in the second year, respectively. SPAD greenness can be used to diagnose spring wheat genotypes differing in flag leaf Chla and total Chl content under warm Mediterranean conditions, but may not always applicable in cooler Mediterranean conditions, where genetic variability, especially in Chlb, was not expressed adequatel

Emergency right hemicolectomy for inflammatory cecal masses mimicking acute appendicitis

Background: Unexpected inflammatory cecal masses of uncertain etiology, encountered in the emergency surgical departments can be indistinguishable, and appropriate operative management of these cases is a dilemma for the surgeons

Emergency right hemicolectomy for inflammatory cecal masses mimicking acute appendicitis

Background: Unexpected inflammatory cecal masses of uncertain etiology, encountered in the emergency surgical departments can be indistinguishable, and appropriate operative management of these cases is a dilemma for the surgeons. Methods: Over a 30-months period between January 2009 and June 2011, a series of 3032 patients who live in sub-urban underwent emergency surgery for clinical diagnosis of acute appendicitis and ileocecal resection or right hemicolectomy for inflammatory cecal mass were performed in 48 patients. Results: 28 men and 20 women from suburban between ages 16-73 presented with right iliac fossa pain. The major presenting symptom was pain in the right iliac fossa (100%). On physical examination; tenderness at or near the McBurney point was detected in 44 (91,6%) patients. The range of the leucocyte level was between 8.000 to 24.000 and mean level is 16.000. After initial laparoscopic exploration, ileocecal resection or right hemicolectomy was performed conservatively because of the uncertainty of the diagnosis. Overall 32 patients underwent ileocecal resection and 16 patients underwent right hemicolectomy. Pathology revealed appendicular phlegmon in 18 patients, perforated cecal diverticulitis in 12 patients, tuberculosis in 6 patients, appendiceal and cecal rupture in 4 patients, malign mesenquimal neoplasm in 4 patients, non-spesific granulomatous in 2 patients and appendecular endometriosis in 2 patients. Conclusion: Most inflammatory cecal masses are due to benign pathologies and can be managed safely and sufficiently with ileocecal resection or right hemicolectomy. The choice of the surgical procedure depends on the experience of the surgical team

Hepatotoxicity associated with statins

Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies. Most of investigations have focused on both these adverse effects and mechanisms of drug induced toxicity. The present review has attempted to compile almost all of the existing studies on the hepatotoxicity of statins but not rhabdomyolysis. The aim of our study is to provide an overview of the studies on the statin-associated hepatotoxicity and to discuss the published studies. The researchers are of the opinion that the research on this topic is incomplete but extremely necessary

Image-Guided Enhanced PDT/PTT Combination Therapy Using Brominated Hemicyanine-Loaded Folate Receptor-Targeting Ag₂S Quantum Dots

Tumor-targeting nanoparticles and phototherapies are the two major trends in tumor-specific, local cancer therapy with minimal side effects. Organic photosensitizers (PSs) usually offer effective photodynamic therapy (PDT) but require enhanced solubility and tumor-targeting, which may be provided by a nanoparticle. Near-infrared (NIR)-emitting Ag2S quantum dots may act as a delivery vehicle for the PS, NIR tracking agent, and as a phototherapy (PTT) agent. A combination of the two provides luminescent dual-phototherapy agents with tumor-specificity and image-guided and enhanced cytotoxicity as a result of synergistic PDT and PTT. In this study, brominated hemicyanine (Hemi-Br), a photosensitizer, was loaded onto folic acid (FA)-tagged, glutathione (GSH)-coated Ag2S quantum dots (AS-GSH QDs) to provide enhanced phototoxicity via a photodynamic and mild photothermal effect in folate receptor(+) cancer cell lines at clinically relevant 640 nm irradiation. Final particles (AS-GSH-FA/Hemi-Br) had a hydrodynamic size of 75.5 nm, dual emission at both 705 and 910 nm, and a 93% light-to-heat conversion efficiency under 640 nm laser irradiation. In vitro cytotoxicity studies were conducted with folate receptor (FR)-positive HeLa and -negative A549 cell lines to differentiate receptor-mediated uptake. Enhanced phototoxicity on HeLa cells was observed with AS-GSH-FA/Hemi-Br compared to free Hemi-Br and AS-GSH-FA QDs due to increased uptake of the photosensitizer via active targeting and combination therapy, which is especially visible at the safe dose of single agents. Upon irradiation with a 640 nm (300 mW, 0.78 W/cm2) laser for 5 min, the viability of the HeLa cells decreased from 64% to 42 and 25% when treated with free Hemi-Br, AS-GSH-FA, and AS-GSH-FA/Hemi-Br, respectively. Overall, AS-GSH-FA/Hemi-Br provides image-guided enhanced PDT/PTT, which may be adopted for different FR(+) tumors

The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries

Background Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. Methods We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1,2017, and Dec 31,2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. Findings The cohort included 4064 children from 149 countries. The median age at diagnosis was 23.2 months (IQR 11.0-36.5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0.8%) of 636 children from high-income countries, 55 (5.4%) of 1027 children from upper-middle-income countries, 342 (19. 7%) of 1738 children from lower-middle-income countries, and 196 (42.9%) of 457 children from low-income countries. Enudeation surgery was available for all children and intravenous chemotherapy was available for 4014 (98.8%) of 4064 children. The 3-year survival rate was 99.5% (95% CI 98.8-100.0) for children from high-income countries, 91.2% (89.5-93.0) for children from upper-middle-income countries, 80.3% (78.3-82.3) for children from lower-middle-income countries, and 57.3% (524-63-0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16.67; 95% CI 4.76-50.00), cT4 advanced tumour compared to cT1 (8.98; 4.44-18.18), and older age at diagnosis in children up to 3 years (1.38 per year; 1.23-1.56). For children aged 3-7 years, the mortality risk decreased slightly (p=0.0104 for the change in slope). Interpretation This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Y