Cold atmospheric plasma enhances morphological and biochemical attributes of tomato seedlings.

Cold atmospheric plasma (CAP) is a physical technology with notable effects on living organisms. In the present study, tomato seeds (Solanum lycopersicum var. Bassimo Mill.) were exposed to CAP for various time intervals, ranging from 1 to 5 min, in both continuous and intermittent periods, and were compared with a control group that received no CAP treatment. Seedlings grown from treated seeds exhibited improvements in levels of growth traits, photosynthetic pigments, and metabolite contents when compared to the control group. Seedlings from seeds treated with S04 displayed significant increases in shoot and root lengths, by 32.45% and 20.60% respectively, compared to the control group. Moreover, seedlings from seeds treated with S01 showed a 101.90% increase in total protein, whereas those treated with S02 experienced a 119.52% increase in carbohydrate content. These findings highlight the substantial improvements in growth characteristics, photosynthetic pigments, and metabolite levels in seedlings from treated seeds relative to controls. Total antioxidant capacity was boosted by CAP exposure. The activities of enzymes including superoxide dismutase, catalase, and peroxidases were stimulated by S02 and exceeded control treatment by (177.48%, 137.41%, and 103.32%), respectively. Additionally, exposure to S04 increased the levels of non-enzymatic antioxidants like flavonoids, phenolics, saponins, and tannins over the control group (38.08%, 30.10%, 117.19%, and 94.44%), respectively. Our results indicate that CAP-seed priming is an innovative and cost-effective approach to enhance the growth, bioactive components, and yield of tomato seedlings.

The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell-Mediated Killing of AML Leukemic Stem Cells.

The prognosis of patients with acute myeloid leukemia (AML) is limited, especially for elderly or unfit patients not eligible for hematopoietic stem cell (HSC) transplantation. The disease is driven by leukemic stem cells (LSCs), which are characterized by clonal heterogeneity and resistance to conventional therapy. These cells are therefore believed to be a major cause of progression and relapse. We designed MP0533, a multispecific CD3-engaging DARPin (designed ankyrin repeat protein) that can simultaneously bind to three antigens on AML cells (CD33, CD123, and CD70), aiming to enable avidity-driven T cell-mediated killing of AML cells co-expressing at least two of the antigens. In vitro, MP0533 induced selective T cell-mediated killing of AML cell lines, as well as patient-derived AML blasts and LSCs, expressing two or more target antigens, while sparing healthy HSCs, blood, and endothelial cells. The higher selectivity also resulted in markedly lower levels of cytokine release in normal human blood compared to single antigen-targeting T-cell engagers. In xenograft AML mouse models, MP0533 induced tumor-localized T-cell activation and cytokine release, leading to complete eradication of the tumors while having no systemic adverse effects. These studies show that the multispecific-targeting strategy used with MP0533 holds promise for improved selectivity towards LSCs and efficacy against clonal heterogeneity, potentially bringing a new therapeutic option to this group of patients with high unmet need. MP0533 is currently being evaluated in a dose-escalation phase 1 study in patients with relapsed or refractory AML (NCT05673057).

Carcinogenesis and Prognostic Utility of Arginine Methylation-Related Genes in Hepatocellular Cancer.

Protein arginine methylation is among the most important post-translational modifications and has been studied in cancers such as those of the lung and breast. However, comparatively less has been investigated regarding hepatocellular carcinoma, with an annual incidence of almost one million cases. Through using in silico methods, this study examined arginine methylation-related gene expression and methylation levels, and alongside network and enrichment analysis attempted to find how said genes can drive tumorigenesis and offer possible therapeutic targets. We found a robust relationship among the selected methylation genes, with ⅞ showing prognostic value regarding overall survival, and a medley of non-arginine methylation pathways also being highlighted through the aforementioned analysis. This study furthers our knowledge of the methylation and expression patterns of arginine histone methylation-related genes, offering jumping points for further wet-lab studies.

Survival and Enrichment Analysis of Epithelial-Mesenchymal Transition Genes in Bladder Urothelial Carcinoma.

The escalating prevalence of bladder cancer, particularly urothelial carcinoma, necessitates innovative approaches for prognosis and therapy. This study delves into the significance of genes related to epithelial-mesenchymal transition (EMT), a process inherently linked to carcinogenesis and comparatively better studied in other cancers. We examined 1184 EMT-related gene expression levels in bladder urothelial cancer cases through the TCGA dataset. Genes shown to be differentially expressed in relation to survival underwent further network and enrichment analysis to uncover how they might shape disease outcomes. Our in silico analysis revealed a subset of 32 genes, including those significantly represented in biological pathways such as VEGF signaling and bacterium response. In addition, these genes interact with genes involved in the JAK-STAT signaling pathway. Additionally, some of those 32 genes have been linked to immunomodulators such as chemokines CCL15 and CCL18, as well as to various immune cell infiltrates. Our findings highlight the prognostic utility of various EMT-related genes and identify possible modulators of their effect on survival, allowing for further targeted wet lab research and possible therapeutic intervention.

Increased Glucagon Immunoreactivity in a Rat Model of Diet-induced Obesity following Sleeve Gastrectomy.

OBJECTIVE: Bariatric surgery is currently the most effective treatment for obesity, and procedures such as Roux-en Y gastric bypass and sleeve gastrectomy (SG) also result in rapid improvements in insulin sensitivity and glucose tolerance. In addition, these procedures cause changes in the secretion of various gut-derived hormones. The role these hormones play in the mechanism of the beneficial effects of bariatric surgery is still debated, but nonetheless, their importance provides inspiration for novel obesity-targeted pharmacotherapies. METHODS: Male Sprague Dawley rats were fed either regular chow or a cafeteria diet to induce obesity. A sub-group of the obese animals then underwent either sham surgery or SG. RESULTS: Following a 4-week recovery period, SG rats weighed significantly less than obese or sham-operated rats. Improvements in glucose tolerance and insulin sensitivity also occurred in the SG group, but these were not always statistically significant. We measured the intracellular lipid content of liver samples and found that obese rats showed signs of non-alcoholic fatty liver disease, which were significantly ameliorated by SG. There were significantly higher glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) responses to a standard mixed meal in the SG group, as well as paradoxically higher glucagon secretion. CONCLUSION: These data highlight the need for more specific anti-glucagon antibodies to characterize the changes in proglucagon-derived peptide concentrations that occur following SG. Further studies are required to determine whether these peptides contribute to the therapeutic effects of SG.

Outcomes of Surgical Repair of Tetralogy of Fallot: A Comparison Between the Adult and Pediatric Population.

Introduction Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Early detection and timely treatment have provided successful repair of the anomaly in the developed world. However, in the developing world, there is still a burden of uncorrected TOF patients reaching adulthood. The goal of this study is to determine whether there is any difference in postoperative complications between adult and pediatric populations following surgical correction for TOF. Methods This study involved all those patients who received primary or secondary surgical repair for TOF in our facility between January 2017 and December 2020. The patients were split according to their age into the pediatric group if they were under 18 years and the adult group if they were 18 years or older. Patients with absent pulmonary valve or pulmonary atresia were not included in this study. Patients with large major aortopulmonary collateral arteries (MAPCA) were also excluded from this study. All patients underwent total correction through a median sternotomy approach. The ventricular septal defect was closed with a Bard knitted fiber patch. The right ventricular outflow tract (RVOT) was augmented by excising muscle bands or fibrous bands in the RVOT. If the annulus was smaller than the 3.5 z score, then a transannular patch was done using an autologous pericardium. The main pulmonary artery was augmented in every surgery using an autologous pericardial patch. All patients were shifted to the ICU on the ventilator and were extubated after fulfillment of the extubation criteria. Postoperative complications measured included re-opening, re-intubation, prolonged ventilation (>24 hours), and mortality within the index hospital admission. The clinical data of all patients were prospectively collected and analyzed using the chi-square test and t-test. A p-value of less than or equal to 0.05 was considered significant. Results The total number of patients was 134. This included 83 males (60.1%). A total of 114 patients who were aged below 18 years were included in the pediatric group, and 20 patients aged equal to or more than 18 years were included in the adult group. The mean average perfusion time in minutes in the adult group was 125.8 and in the pediatric group, it was 98.79. Similarly, the mean average of the cross-clamp time was also longer in the adult group at 89.55 minutes versus 69.63 minutes in the pediatric group. Overall, in the adult group, three (15%) patients had postoperative complications, while in the pediatric group, a total of 14 (11.9%) patients had postoperative complications (p = 0.001). However, there was no significant difference in the number of re-openings (8.5% vs. 10%; p = 0.8). The total mortality observed was 16 (11.59%). This included 14 (11.9%) in the pediatric group and two (10%) in the adult group. There was no significant difference between the two groups (p = 0.8). Conclusions Surgical repair of TOF can be performed in both adult and pediatric populations with acceptable outcomes. The mortality rate was found to be slightly greater in the pediatric population compared to the adults. However, it can be seen that the number of postoperative complications is greater in adults. Further research is needed to optimize outcomes for both pediatric and adult patients with TOF.

Regulation of SELENOF translation by eIF4a3: Possible role in prostate cancer progression.

The levels of the SELENOF selenoprotein are dramatically reduced in prostate cancer compared to adjacent benign tissue and reducing SELENOF in prostate epithelial cells results in the acquisition of features of the transformed phenotype. It was hypothesized that the aberrant increase in the eiF4a3 translation factor, which has an established role in RNA splicing and the regulation of selenoprotein translation, contributes to the lower levels of SELENOF. Using the available databases, eIF4a3 messenger RNA (mRNA) levels are elevated in prostate cancer compared to normal tissue as is the hypomethylation of the corresponding gene. Using a prostate cancer tissue microarray, we established that eiF4a3 levels are higher in prostate cancer tissue. Ectopic expression of eIF4a3 in prostate cancer cells reduced SELENOF levels and attenuated the readthrough of the UGA codon using a specialized reporter construct designed to examine UGA decoding, with the opposite effects observed using eIF4a3 knock-down constructs. Direct binding of eIF4a3 to the regulatory regions of SELENOF mRNA was established with pull-down experiments. Lastly, we show that an eIF4a3 inhibitor, eIF4a3-IN-2, increases SELENOF levels, UGA readthrough, and reduces binding of eIF4a3 to the SELENOF mRNA 3'-UTR in exposed cells. These data establish eIF4a3 as a likely prostate cancer oncogene and a regulator of SELENOF translation.

Biocontrol agent of root-knot nematode Meloidogyne javanica and root-rot fungi, Fusarium solani in okra morphological, anatomical characteristics and productivity under greenhouse conditions.

This study was conducted to evaluate the ability of some fungal culture filtrate, as biocontrol agents against okra wilt caused by Fusarium solani. and Meloidogyne javanica. In the present study, fungal culture filtrates (FCFs) of Aspergillus terreus (1), Aspergillus terreus (2), Penicillium chrysogenum, and Trichoderma spp. were tested against M. javanica in vitro. The effects of P. chrysogenum and Trichoderma spp. (FCFs) in controlling root-rot fungi and root-knot nematode disease complex on okra plants were studied under greenhouse conditions (In vivo). In vitro experiment, the results revealed cumulative rate of J2s mortality of M. javanica reached to 97.67 and 95% by P. chrysogenum and Trichoderma spp., respectively, after 72 h. incubation. Additionally, Trichoderma spp exhibited the most effective inhibitory activity against the pathogen's radial growth, with a percentage of 68%. P. chrysogenum ranked second with 53.88%, while A. terreus (2) demonstrated the weakest inhibitory effect of 24.11%. T6 [Nematode infection (M. javanica) + Fungus infection (F. solani) + Overflowed with fungal culture filtrate (P. chrysogenum)] and T8 [Nematode infection (M. javanica) + Fungus infection (F. solani) + spray with fungal culture filtrate (P. chrysogenum)] had the greatest effects on nematode galling indices on okra roots and substantially reduced the reproductive factors in the greenhouse (In vivo experiment). T6 was the best treatment to decrease disease severity, as reached (28%) relatively. On the other hand, T12 [(Fungus infection (F. solani) + (Dovex 50% fungicide with irrigation water)] recorded the lowest disease severity reaching (8%) relatively. The results showed that nematode infection or fungus infection or both decreased all studied anatomical characteristics of okra root, stem, and leaves. We concluded from this study that root-knot nematode and root-rot fungi were reduced by using fungal culture filtrates and could improve plant growth.

Unusual Fungal Endocarditis Causing Disseminated Infection After Renal Transplant.

Fungal endocarditis is a relatively uncommon disease; it mostly affects those with intracardiac devices and those with compromised immune systems. Scedosporium apiospermum (S. apiospermum), the asexual state of Pseudoallescheria boydii, has become increasingly reported as an opportunistic pathogen. These filamentous fungi present in soil, sewage, and polluted waters, and was previously recognized to cause human infection after their inhalation or traumatic subcutaneous implantation. In immunocompetent individuals, it usually causes localized diseases depending on the site of entry such as skin mycetoma. However, in immunocompromised hosts, the fungus species appear to disseminate and cause invasive infections, frequently reported to be life-threatening with poor response to antifungal medications. S. apiospermum invasive endocarditis remains a rare complication, mostly cited in immunocompetent hosts with prosthetic cardiac valves or other intracardiac devices and severely immunocompromised patients with hematologic neoplasia. Herein, we describe the case of a renal transplant patient on immunosuppressive medications who presented with S. apiospermum fungal septic infection that invaded the left ventricular outflow tract (LVOT) causing endocarditis with disseminated infection and resulted in poor clinical outcome.

Associations of selenoprotein expression and gene methylation with the outcome of clear cell renal carcinoma.

Selenoproteins are a ubiquitous class of proteins defined by having a selenocysteine amino acid residue. While many of the selenoproteins have been well characterized with important roles in oxidation-reduction reactions and hormone synthesis among others, there exist some whose biological roles are not as well understood as denoted by the "SELENO" root. In this study, we explored associations between the reported RNA levels of "SELENO" proteins and clear cell renal cell carcinoma (ccRCC), the most common subtype of renal carcinoma in the US. Utilizing The Cancer Genome Atlas (TCGA) alongside other in silico tools, we discovered higher mRNA expression of Selenoprotein I, T, and P was associated with better overall survival outcomes and differential expression of other selenoproteins based on tumor stage. Additionally, we uncovered relative hypomethylation among selenoproteins in primary ccRCC tumor samples compared to normal tissue. Network and enrichment analysis showed numerous genes through which selenoproteins may modulate cancer progression and outcomes such as DERL1, PNPLA2/3, MIEN1, and FOXO1 which have been well-described in other cancers. In light of our findings highlighting an association of selenoprotein methylation and expression patterns with ccRCC outcome, further wet lab research is warranted.

Guanfacine Normalizes the Overexpression of Presynaptic α-2A Adrenoceptor Signaling and Ameliorates Neuropathic Pain in a Chronic Animal Model of Type 1 Diabetes.

BACKGROUND: Diabetes is associated with several complications, including neuropathic pain, which is difficult to manage with currently available drugs. Descending noradrenergic neurons possess antinociceptive activity; however, their involvement in diabetic neuropathic pain remains to be explored. METHODS: To infer the regulatory role of this system, we examined as a function of diabetes, the expression and localization of alpha-2A adrenoceptors (α2-AR) in the dorsal root ganglia and key regions of the central nervous system, including pons and lumbar segment of the spinal cord using qRT-PCR, Western blotting, and immunofluorescence-based techniques. RESULTS: The data revealed that presynaptic synaptosomal-associated protein-25 labeled α2-AR in the central and peripheral nervous system of streptozotocin diabetic rats was upregulated both at the mRNA and protein levels. Interestingly, the levels of postsynaptic density protein-95 labeled postsynaptic neuronal α2-AR remained unaltered as a function of diabetes. These biochemical abnormalities in the noradrenergic system of diabetic animals were associated with increased pain sensitivity as typified by the presence of thermal hyperalgesia and cold/mechanical allodynia. The pain-related behaviors were assessed using Hargreaves apparatus, cold-plate and dynamic plantar aesthesiometer. Chronically administered guanfacine, a selective α2-AR agonist, to diabetic animals downregulated the upregulation of neuronal presynaptic α2-AR and ameliorated the hyperalgesia and the cold/mechanical allodynia in these animals. CONCLUSION: Together, these findings demonstrate that guanfacine may function as a potent analgesic and highlight α2-AR, a key component of the descending neuronal autoinhibitory pathway, as a potential therapeutic target in the treatment of diabetic neuropathic pain.

Enhancement of photosynthesis efficiency and yield of strawberry (Fragaria ananassa Duch.) plants via LED systems.

Due to advances in the industrial development of light-emitting diodes (LEDs), much research has been conducted in recent years to get a better understanding of how plants respond to these light sources. This study investigated the effects of different LED-based light regimes on strawberry plant development and performance. The photosynthetic pigment content, biochemical constituents, and growth characteristics of strawberry plants were investigated using a combination of different light intensities (150, 200, and 250 µmol m-2 s-1), qualities (red, green, and blue LEDs), and photoperiods (14/10 h, 16/8 h, and 12/12 h light/dark cycles) compared to the same treatment with white fluorescent light. Plant height, root length, shoot fresh and dry weight, chlorophyll a, total chlorophyll/carotenoid content, and most plant yield parameters were highest when illuminated with LM7 [intensity (250 µmol m-2 s-1) + quality (70% red/30% blue LED light combination) + photoperiod (16/8 h light/dark cycles)]. The best results for the effective quantum yield of PSII photochemistry Y(II), photochemical quenching coefficient (qP), and electron transport ratio (ETR) were obtained with LM8 illumination [intensity (250 µmol m-2 s-1) + quality (50% red/20% green/30% blue LED light combination) + photoperiod (12 h/12 h light/dark cycles)]. We conclude that strawberry plants require prolonged and high light intensities with a high red-light component for maximum performance and biomass production.

Changes in the expression of meteorin-like (METRNL), irisin (FNDC5), and uncoupling proteins (UCPs) after bariatric surgery.

OBJECTIVE: Bariatric surgery is currently the most effective treatment for severe obesity. This study aims to investigate the changes in expression levels of meteorin-like protein (METRNL), irisin (FNDC5), and uncoupling proteins (UCP) 1/2/3 following bariatric surgery to understand their involvement in enhancing metabolism after surgery. METHOD: A total of 40 participants were enrolled in this interventional study, 20 with obesity BMI ≥ 35 kg/m2 and 20 with BMI ≤ 25 kg/m2 . Bariatric surgery (laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) was performed. The levels of various molecules of interest were analyzed before and after surgery. RESULTS: Gene expression analysis revealed significantly higher levels of METRNL, UCP1, and UCP3 in individuals with obesity when compared with healthy individuals before surgery (p < 0.05). Gene expression levels of METRNL and UCP2 showed a significant increase after bariatric surgery (p < 0.05). METRNL plasma level was significantly higher in individuals with obesity before surgery (mean [SEM], 55,222.6 [1,421.1] pg/mL, p = 0.0319), as well as at 6 and 12 months (57,537.3 [1,303.9] pg/mL, p = 0.0005; 59,334.9 [1,214.3] pg/mL, p < 0.0001) after surgery. CONCLUSION: The changes in the levels of various molecules of interest support their possible involvement in the inflammatory and thermogenic responses following bariatric surgery.

Increasing the performance of cucumber (Cucumis sativus L.) seedlings by LED illumination.

Light is one of the most important limiting factors for photosynthesis and the production of plants, especially in the regions where natural environmental conditions do not provide sufficient sunlight, and there is a great dependence on artificial lighting to grow plants and produce food. The influence of light intensity, quality, and photoperiod on photosynthetic pigments content and some biochemical and growth traits of cucumber seedlings grown under controlled conditions was investigated. An orthogonal design based on a combination of different light irradiances, ratio of LEDs and photoperiods was used. Treaments consisted of three light irradiance regimes (80, 100, and 150 µmol m-2 s-1) provided by light-emitting diodes (LEDs) of different ratios of red and blue (R:B) (30:70, 50:50, and 70:30) and three different photoperiods (10/14, 12/12, and 14/10 h). The white light was used as a control/reference. Plant height, hypocotyl length, stem diameter, leaf area, and soluble sugar content were highest when exposed to LM9 (150 µmol m-2 s-1; R70:B30; 12/12 h) light mode, while the lowest values for the above parameters were obtained under LM1 (80 µmol m-2 s-1; R30:B70; 10/14 h). Higher pigments contents (chlorophyll a, chlorophyll b, and carotenoid) were obtained when light regime LM9 (150 µmol m-2 s-1; R70:B30; 12/12 h) was applied. In general, cucumber seedlings grown under the LM9 regime showed a significant increase in growth as well as photosynthetic capacity. It seems that the content of photosynthetic pigments is the key factor responsible for the performance of cucumber seedlings grown under different lighting modes, compared to other traits studied. We recommend monitoring the content of chlorophyll a, b, and their ratio value when studying the light requirement of cucumber plants.

Association Between Factors Involved in Bone Remodeling (Osteoactivin and OPG) With Plasma Levels of Irisin and Meteorin-Like Protein in People With T2D and Obesity.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various molecules involved in bone remodeling in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic (ND) and 104 T2D. A Multiplex assay was used to assess the level of various osteogenic molecules namely osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to ND individuals (p ≤ 0.05). Using Spearman's correlation, a positive correlation was observed between irisin and Osteoactivin as well as OPG (p < 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p < 0.05). The strong positive association shown in this study between irisin, METRNL and various molecules with osteogenic properties emphasize a possible interaction between these organs. This report suggests that having a dysregulation in the level of the aforementioned molecules could potentially affect the development of bone and muscle related complications that are associated with obesity and T2D.

GenACO a multi-objective cached data offloading optimization based on genetic algorithm and ant colony optimization.

BACKGROUND: Data exchange and management have been observed to be improving with the rapid growth of 5G technology, edge computing, and the Internet of Things (IoT). Moreover, edge computing is expected to quickly serve extensive and massive data requests despite its limited storage capacity. Such a situation needs data caching and offloading capabilities for proper distribution to users. These capabilities also need to be optimized due to the experience constraints, such as data priority determination, limited storage, and execution time. METHODS: We proposed a novel framework called Genetic and Ant Colony Optimization (GenACO) to improve the performance of the cached data optimization implemented in previous research by providing a more optimum objective function value. GenACO improves the solution selection probability mechanism to ensure a more reliable balancing of the exploration and exploitation process involved in finding solutions. Moreover, the GenACO has two modes: cyclic and non-cyclic, confirmed to have the ability to increase the optimal cached data solution, improve average solution quality, and reduce the total time consumption from the previous research results. RESULT: The experimental results demonstrated that the proposed GenACO outperformed the previous work by minimizing the objective function of cached data optimization from 0.4374 to 0.4350 and reducing the time consumption by up to 47%.

Microarray analysis reveals ONC201 mediated differential mechanisms of CHOP gene regulation in metastatic and nonmetastatic colorectal cancer cells.

The imipramine ONC201 has antiproliferative effects in several cancer cell types and activates integrated stress response pathway associated with the induction of Damage Inducible Transcript 3 (DDIT3, also known as C/EBP homologous protein or CHOP). We investigated the signaling pathways through which ONC201/CHOP crosstalk is regulated in ONC201-treated nonmetastatic and metastatic cancer cell lines (Dukes' type B colorectal adenocarcinoma nonmetastatic SW480 and metastatic LS-174T cells, respectively). Cell proliferation and apoptosis were evaluated by MTT assays and flow cytometry, gene expression was assessed by Affymetrix microarray, signaling pathway perturbations were assessed in silico, and key regulatory proteins were validated by Western blotting. Unlike LS-174T cells, SW480 cells were resistant to ONC201 treatment; Gene Ontology analysis of differentially expressed genes showed that cellular responsiveness to ONC201 treatment also differed substantially. In both ONC201-treated cell lines, CHOP expression was upregulated; however, its upstream regulatory mechanisms were perturbed. Although, PERK, ATF6 and IRE1 ER-stress pathways upregulated CHOP in both cell types, the Bak/Bax pathway regulated CHOP only LS-174T cells. Additionally, CHOP RNA splicing profiles varied between cell lines; these were further modified by ONC201 treatment. In conclusion, we delineated the signaling mechanisms by which CHOP expression is regulated in ONC201-treated non-metastatic and metastatic colorectal cell lines. The observed differences could be related to cellular plasticity and metabolic reprogramming, nevertheless, detailed mechanistic studies are required for further validations.

Effects of light spectrum on morpho-physiological traits of grafted tomato seedlings.

It is already known that there are many factors responsible for the successful grafting process in plants, including light intensity. However, the influence of the spectrum of light-emitting diodes (LEDs) on this process has almost never been tested. During the pre-grafting process tomato seedlings grew for 30 days under 100 µmol m-2 s-1 of mixed LEDs (red 70%+ blue 30%). During the post-grafting period, seedlings grew for 20 days under the same light intensity but the lightening source was either red LED, mixed LEDs (red 70% + blue 30%), blue LED or white fluorescent lamps. This was done to determine which light source(s) could better improve seedling quality and increase grafting success. Our results showed that application of red and blue light mixture (R7:B3) caused significant increase in total leaf area, dry weight (total, shoot and root), total chlorophyll/carotenoid ratio, soluble protein and sugar content. Moreover, this light treatment maintained better photosynthetic performance i.e. more effective quantum yield of PSII photochemistry Y(II), better photochemical quenching (qP), and higher electron transport rate (ETR). This can be partially explained by the observed upregulation of gene expression levels of PsaA and PsbA and the parallel protein expression levels. This in turn could lead to better functioning of the photosynthetic apparatus of tomato seedlings and then to faster production of photoassimilate ready to be translocated to various tissues and organs, including those most in need, i.e., involved in the formation of the graft union.

Effect of sleeve gastrectomy on the expression of meteorin-like (METRNL) and Irisin (FNDC5) in muscle and brown adipose tissue and its impact on uncoupling proteins in diet-induced obesity rats.

BACKGROUND: Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves metabolic homeostasis by modulating energy expenditure and enhancing thermogenesis through increasing the expression level of meteorin-like protein (METRNL) and fibronectin type III domain-containing protein 5 (FNDC5/Irisin) through uncoupling proteins 1/2/3 (UCP1, UCP2, and UCP3). OBJECTIVES: To study the effect of SG on the levels of proteins involved in thermogenesis process. SETTING: Laboratory rats at Kuwait University. METHODS: Male Sprague-Dawley rats, aged 4 to 5 weeks, were divided into 2 groups, control (n = 11) and diet-induced obesity (DIO) (n = 22). The control group was fed regular rat chow ad libitum, whereas the DIO group was fed cafeteria diet "high-fat/carbohydrate diet" ad libitum. At 21 weeks, rats in the DIO group that weighed 20% more than the control group animals underwent surgery. These rats were randomly subdivided into Sham and SG operation groups. Gene expression was evaluated, and enzyme-linked immunosorbent assays were employed to assess the changes in gene and protein levels in tissue and circulation. RESULTS: The protein expression data revealed an increase in METRNL levels in the muscles and white adipose tissue of SG animals. METRNL level in circulation in SG animals was reduced compared with control and Sham rats. The level of Irisin increased in the muscle of SG animals compared with the control and Sham group animals; however, a decrease in Irisin level was observed in the white adipose tissue and brown adipose tissue of SG animals compared with controls. Gene expression analysis revealed decreased METRNL levels in muscle tissues in the SG group compared with the control group animals. Increased expression of FNDC5 (Irisin), UCP2, and UCP3 in the muscle tissue of SG animals was also observed. Furthermore, the levels of UCP1, UCP2, UCP3, and METRNL in the brown adipose tissue of SG animals were upregulated. No significant alteration in the gene expression of Irisin was observed in brown adipose tissue. CONCLUSIONS: Sleeve gastrectomy induces weight loss through complex mechanisms that may include browning of fat.

Evolution of Patiromer Use: a Review.

PURPOSE OF REVIEW: The purpose of this review is to present data from clinical trials that resulted in the key data supporting the use of patiromer as a potassium binder in clinical practice today. RECENT FINDINGS: In addition to trials that support the current Food and Drug Administration label and published over the past 3 years, the recently published Spironolactone With Patiromer in the Treatment of Resistant Hypertension in Chronic Kidney Disease (AMBER) trial provides clear benefits of patiromer use in a group of resistant hypertension patients. The AMBER was a phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled study that evaluated 295 participants stratified by local serum potassium measurement (4.3 to < 4.7 mmol/L vs 4.7 to 5.1 mmol/L) and history of diabetes and chronic kidney disease. The focus was on enabling participants with resistant hypertension to achieve blood pressure goals by using spironolactone. Additionally, the ongoing Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure (DIAMOND) trial is designed to demonstrate how patiromer is an "enabler" of therapies that are needed to either control resistant hypertension or reduce mortality in heart failure but generate hyperkalemia. These and other studies are discussed in detail. Patiromer is one of two new potassium binders that are far better tolerated than the previous agent and can be given chronically to participants who need life-saving therapies but have elevations of potassium into a dangerous range as a consequence.