Surface Passivation of Carbon Dots for Tunable Biological Performance.

Recent investigations were shifted this trend toward exploring the biomedical applicability of CDs, relevant to chronic diseases. Herein, a systematic approach is demonstrated for studying the effect of variation in the surface passivation of CDs for tuning its optical character and biological performance. Alginate and pectin were successfully clustered oxygen-surface passivated CDs, while, chitin was used to nucleate nitrogen-surface passivated CDs. Pectin-treated with base (4.1 ± 1.8 nm) and chitin-treated acid (3.5 ± 1.7 nm) were ingrained the smallest O-surface passivated CDs and N-surface passivated CDs, respectively. However, N-surface passivated CDs were shown with the highest optical activity. CDs colloids prepared from alginate, pectin & chitin, resulted in reduction of tumor cell viability percentage to be 80.8%, 74.0% & 69.0% respectively. O-surface passivated CDs nucleated from alginate showed the highest anti-proliferative effects. Moreover, O-surface passivated CDs (from alginate) showed the supremacy in inhibition of inflammation, while, increasing of its concentration ten times resulted in significant increment in inhibition percent to be 28% & 42%, using 1 µg/mL & 10 µg/mL, respectively. In summarization, it could be decided that, compared to N-surface passivated CDs (from chitin), O-surface passivated CDs (from alginate) showed excellency in application as a concurrent anti-inflammatory/antitumor drug, to be applied as a potential therapeutical reagent for treatment of inflammation, in production of vaccines, immune-therapeutics, and immune-suppressive drugs.

A Case-based Implementation of Heart Failure Therapies, a Consensus Pathway by the Saudi Heart Failure Working Group.

The implementation of guideline-directed medical therapy (GDMT) in heart failure (HF) has many challenges in real-world clinical practice. The consensus document is written considering the variability of the clinical presentation of HF patients. HF medical therapies need frequent dose adjustment during hospital admission or when patients develop electrolyte imbalance, acute kidney injury, and other acute illnesses. The paper describes clinical scenarios and graphs that will aid the managing physicians in decision-making for HF therapy optimization.

Tracking the therapeutic efficacy of a ketone mono ester and ß-hydroxybutyrate for ulcerative colitis in rats: New perspectives.

Ulcerative colitis (UC) is an inflammatory condition that affects the colon's lining and increases the risk of colon cancer. Despite ongoing research, there is no identified cure for UC. The recognition of NLRP3 inflammasome activation in the pathogenesis of UC has gained widespread acceptance. Notably, the ketone body ß-hydroxybutyrate inhibits NLRP3 demonstrating its anti-inflammatory properties. Additionally, BD-AcAc 2 is ketone mono ester that increases ß-hydroxybutyrate blood levels. It has the potential to address the constraints associated with exogenous ß-hydroxybutyrate as a therapeutic agent, including issues related to stability and short duration of action. However, the effects of ß-hydroxybutyrate and BD-AcAc 2 on colitis have not been fully investigated. This study found that while both exogenous ß-hydroxybutyrate and BD-AcAc 2 produced the same levels of plasma ß-hydroxybutyrate, BD-AcAc 2 demonstrated superior effectiveness in mitigating dextran sodium sulfate-induced UC in rats. The mechanism of action involves modulating the NF-κB signaling, inhibiting the NLRP3 inflammasome, regulating antioxidant capacity, controlling tight junction protein expression and a potential to inhibit apoptosis and pyroptosis. Certainly, BD-AcAc 2's anti-inflammatory effects require more than just increasing plasma ß-hydroxybutyrate levels and other factors contribute to its efficacy. Local ketone concentrations in the gastrointestinal tract, as well as the combined effect of specific ketone bodies, are likely to have contributed to the stronger protective effect observed with ketone mono ester ingestion in our experiment. As a result, further investigations are necessary to fully understand the mechanisms of BD-AcAc 2 and optimize its use.

Nano-scaled polyacrylonitrile for industrialization of nanofibers with photoluminescence and microbicide performance.

Nanofibers are investigated to be superiorly applicable in different purposes such as drug delivery systems, air filters, wound dressing, water filters, and tissue engineering. Herein, polyacrylonitrile (PAN) is thermally treated for autocatalytic cyclization, to give optically active PAN-nanopolymer, which is subsequently applicable for preparation of nanofibers through solution blow spinning. Whereas, solution blow spinning is identified as a process for production of nanofibers characterized with high porosity and large surface area from a minimum amounts of polymer solution. The as-prepared nanofibers were shown with excellent photoluminescence and microbicide performance. According to rheological properties, to obtain spinnable PAN-nanopolymer, PAN (12.5-15% wt/vol, honey like solution, 678-834 mPa s), thermal treatment for 2-4 h must be performed, whereas, time prolongation resulted in PAN-nanopolymer gelling or rubbering. Size distribution of PAN-nanopolymer (12.5% wt/vol) is estimated (68.8 ± 22.2 nm), to reflect its compatibility for the production of carbon nanofibers with size distribution of 300-400 nm. Spectral mapping data for the photoluminescent emission showed that, PAN-nanopolymer were exhibited with two intense peaks at 498 nm and 545 nm, to affirm their superiority for production of fluorescent nanofibers. The microbial reduction % was estimated for carbon nanofibers prepared from PAN-nanopolymer (12.5% wt/vol) to be 61.5%, 71.4% and 81.9%, against S. aureus, E. coli and C. albicans, respectively. So, the prepared florescent carbon nanofibers can be potentially applicable in anti-infective therapy.

Imaging Reactive Oxygen Radicals in Excised Mouse Lung Trapped by Reaction with Hydroxylamine Probes Using 1 GHz Rapid Scan Electron Paramagnetic Resonance.

PURPOSE: Oxidative stress is proposed to be critical in acute lung disease, but methods to monitor radicals in lungs are lacking. Our goal is to develop low-frequency electron paramagnetic resonance (EPR) methods to monitor radicals that contribute to the disease. PROCEDURES: Free radicals generated in a lipopolysaccharide-induced mouse model of acute respiratory distress syndrome reacted with cyclic hydroxylamines CPH (1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride) and DCP-AM-H (4-acetoxymethoxycarbonyl-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid), which were converted into the corresponding nitroxide radicals, CP• and DCP•. The EPR signals of the nitroxide radicals in excised lungs were imaged with a 1 GHz EPR spectrometer/imager that employs rapid scan technology. RESULTS: The small numbers of nitroxides formed by reaction of the hydroxylamine with superoxide result in low signal-to-noise in the spectra and images. However, since the spectral properties of the nitroxides are known, we can use prior knowledge of the line shape and hyperfine splitting to fit the noisy data, yielding well-defined spectra and images. Two-dimensional spectral-spatial images are shown for lung samples containing (4.5 ± 0.5) ×1014 CP• and (9.9 ± 1.0) ×1014 DCP• nitroxide spins. These results suggest that a probe that accumulates in cells gives a stronger nitroxide signal than a probe that is more easily washed out of cells. CONCLUSION: The nitroxide radicals in excised mouse lungs formed by reaction with hydroxylamine probes CPH and DCP-AM-H can be imaged at 1 GHz.

Pyrimidine-5-carbonitrile derivatives as sprout for CQDs proveniences: Antitumor and anti-inflammatory potentiality.

A comparative study is proposed to show the effect of variation in the heteroatoms in the main skeleton of CQDs proveniences, on their affinity for nucleation of CQDs, as anti-inflammatory and anticancer drugs. Heterocyclic-based CQDs sprout was successfully exploited for preparation of three CQDs proveniences, named as; 2-(2,5-dimethoxyphenyl)-4,6-dioxo-6,11-dihydro-4H-pyrimido[2,1-b] quinazoline-3-carbonitrile (compound A), 2-(2,5-dimethoxyphenyl)-4,6-dioxo-4H,6H-benzo[e]pyrimido[2,1-b][1,3]oxazine-3-carbonitrile (compound S) and 2-(2,5-dimethoxyphenyl)-4,6-dioxo-4H,6H-benzo[e]pyrimido[2,1-b][1,3] thiazine-3-carbonitrile (compound T). Chemical formulas of CQDs proveniences & CQDs were verified via FTIR, 1HNMR, 13CNMR & XRD. Particle size of TM-CQDs, A-CQDs, S-CQDs & T-CQDs were estimated to be 3.7 ± 1.4, 4.6 ± 1.6, 5.9 ± 1.6 nm and 3.0 ± 1.3 nm, respectively. All of CQDs proveniences & CQDs were examined for their affinity as anti-inflammatory drugs via Griess assay. CQDs ingrained from TM (TM-CQDs) were detected with the highest NO inhibition% by increasing its concentration from 10 up to 100 µM to be 40 % to 89 %, respectively. Moreover, their anti-tumor performance against MCF-7: breast Adenocarcinoma cell line was approved via sulforhodamine B assay, whereas, IC50 was evaluated for TM-CQDs, A-CQDs, S-CQDs and T-CQDs to be 38.16, 36.09, 100 and 100 µg/ml, respectively.

Involvement of silver and palladium with red peanuts skin extract for cotton functionalization.

A systematic study is currently demonstrated approach for approving the superior role of silver and palladium metallic particles in acting the role of mordant with acquiring the dyed cotton fabrics excellence in color fastness with additional functions of antimicrobial potentiality and UV-protection action. Whereas, samples were dyed with extract of red peanuts skin as natural textile colorant (RPN dye). The represented data revealed that, in absence of mordant, the samples treated with metal precursors prior to dyeing were exhibited with the excellent color strength, color fastness, antimicrobial action and UV-protection action. Color fastness (washing, rubbing and light fastness) was estimated to be in the range of very good-excellent. Sample pretreated with silver salt and dyed in the absence of mordant was graded with excellent UV-protection action (UPF 31.5, UVB T% 2.6% and UVB blocking percent 97.4%). Antimicrobial potency against E. coli, S. aureus and Candida albicans through inhibition zone and the reduction percent was approved to be in the range of excellence (93.01-99.51%) for the samples dyed in absence of mordant and pretreated with either silver or palladium precursors.

Selective separation of chlorophyll-a using recyclable hybrids based on Zn-MOF@cellulosic fibers.

Chlorophyll-a as pigments, exist in the green organelles for plants that act in photosynthesis. Different studies were considered with demonstration of an effective separation technique of Chlorophyll-a without decomposition; however, the reported methods were disadvantageous with expensiveness and low quantum yield. The current work uniquely represents an investigative method for the separation of Chlorophyll-a from spinach extract using cellulosic hybrids based on ZIF-8 @cellulosic fibers (Zn-zeolitic imidazolate frameworks@cellulosic fibers) as a cost effective and recyclable absorbents. To obtain hybrids, ZIF-8 was in-situ prepared over the cellulosic fibers (bamboo, modal and cotton). The untreated and treated fibers were well characterized via FTIR, SEM, EDX, XRD, in order to approve the successive impregnation of ZIF-8. Whereas, the microscopic images showed that, microcrystalline ZIF-8 rods with length of 1.3-4.4 µm were grown over the cellulosic fibers. The obtained hybrids and the untreated fibers were exploited in the separation of Chlorophyll-a via the adsorption/desorption process. The chlorophyll-adsorption was followed Langmuir isotherm and pseudo-second order model. The Langmuir maximum capacities of Chlorophyll-a onto hybrids were followed the order of ZIF-8@cotton (583.6 mg/g) > ZIF-8@modal (561.3 mg/g) > ZIF-8@bamboo (528.7 mg/g). After incorporation of ZIF-8, the maximum adsorption capacities of cellulosic fibers were enhanced by 1.4-1.9 times. Adsorption of chlorophyll onto the applied hybrids was lowered by 27-28%, after five repetitive washing cycles. The data summarized that; chlorophyll was effectively separated by the synthesized ZIF-8@cellulosic fibers hybrids, whereas, the prepared hybrids showed good reusability for application on wider scaled purposes.

STA9090 as a Potential Therapeutic Agent for Liver Fibrosis by Modulating the HSP90/TßRII/Proteasome Interplay: Novel Insights from In Vitro and In Vivo Investigations.

Liver fibrosis is a progressive condition characterized by the build-up of fibrous tissue resulting from long-term liver injury. Although there have been advancements in research and treatment, there is still a need for effective antifibrotic medication. HSP90 plays a crucial role in the development of fibrosis. It acts as a molecular chaperone that assists in the proper folding and stability of TßRII, potentially regulating the signaling of TGF-ß1. It has been established that TßRII can be degraded through the proteasome degradation system, either via ubiquitination-dependent or -independent pathways. In the present study, STA9090 demonstrated promising effects in both in vitro and in vivo models. It reduced LDH leakage, prolonged the survival rate of hepatocytes in rats with liver fibrosis, and improved liver function. Importantly, STA9090 exerted pleiotropic effects by targeting proteins involved in limiting collagen production, which resulted in improved microscopic features of the rat livers. Our findings suggest that STA9090-induced inhibition of HSP90 leads to the degradation of TßRII, a fibrogenic client protein of HSP90, through the activation of the 20S proteasomal degradation system. We also revealed that this degradation mechanism is not dependent on the autophagy-lysosomal pathway. Additionally, STA9090 was found to destabilize HIF-1α and facilitate its degradation, leading to the reduced transcription of VEGF. Moreover, STA9090's ability to deactivate the NFκB signaling pathway highlights its potential as an anti-inflammatory and antifibrotic agent. However, further research is necessary to fully elucidate the underlying mechanisms and fully capitalize on the therapeutic benefits of targeting HSP90 and associated pathways.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Use of Electron Paramagnetic Resonance (EPR) to Evaluate Redox Status in a Preclinical Model of Acute Lung Injury.

PURPOSE: Patients with hyper- vs. hypo-inflammatory subphenotypes of acute respiratory distress syndrome (ARDS) exhibit different clinical outcomes. Inflammation increases the production of reactive oxygen species (ROS) and increased ROS contributes to the severity of illness. Our long-term goal is to develop electron paramagnetic resonance (EPR) imaging of lungs in vivo to precisely measure superoxide production in ARDS in real time. As a first step, this requires the development of in vivo EPR methods for quantifying superoxide generation in the lung during injury, and testing if such superoxide measurements can differentiate between susceptible and protected mouse strains. PROCEDURES: In WT mice, mice lacking total body extracellular superoxide dismutase (EC-SOD) (KO), or mice overexpressing lung EC-SOD (Tg), lung injury was induced with intraperitoneal (IP) lipopolysaccharide (LPS) (10 mg/kg). At 24 h after LPS treatment, mice were injected with the cyclic hydroxylamines 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride (CPH) or 4-acetoxymethoxycarbonyl-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid (DCP-AM-H) probes to detect, respectively, cellular and mitochondrial ROS - specifically superoxide. Several probe delivery strategies were tested. Lung tissue was collected up to one hour after probe administration and assayed by EPR. RESULTS: As measured by X-band EPR, cellular and mitochondrial superoxide increased in the lungs of LPS-treated mice compared to control. Lung cellular superoxide was increased in EC-SOD KO mice and decreased in EC-SOD Tg mice compared to WT. We also validated an intratracheal (IT) delivery method, which enhanced the lung signal for both spin probes compared to IP administration. CONCLUSIONS: We have developed protocols for delivering EPR spin probes in vivo, allowing detection of cellular and mitochondrial superoxide in lung injury by EPR. Superoxide measurements by EPR could differentiate mice with and without lung injury, as well as mouse strains with different disease susceptibilities. We expect these protocols to capture real-time superoxide production and enable evaluation of lung EPR imaging as a potential clinical tool for subphenotyping ARDS patients based on redox status.

Myopia Progression Among School-Aged Children in the COVID-19 Distance-Learning Era.

Objective: To investigate the effect of online learning and other environmental factors on myopia progression during the Coronavirus pandemic (COVID-19). Methods: A retrospective cohort study from 2018 to 2021. Data from children aged 6-14 were gathered during three visits: pre-pandemic, at the beginning, and during the pandemic. Demographics (hours spent on screens for educational, recreational purposes, outdoors, and type of screen), best-corrected distance visual acuity (BCDVA), uncorrected distance visual acuity (UCDVA), and cycloplegic refraction were gathered. Results: Of 150 patients, 70 [47%] were boys. The mean age was 11 (2.4) years. Participants mainly used mobile phones (62%) and had insufficient outdoor play (88%). Of the 300 eyes, 221 (74%) showed myopia progression. A significant difference in spherical equivalent (SE) was found between pre-pandemic and post-pandemic periods (-0.29 (0.23) D vs -0.40 (0.11) D; p =0.023). Additionally, UCDVA showed a difference between the initial and 1st follow-up visits (0.57 (0.37) vs 0.64 (0.36), p =0.001), and the first and 2nd follow-up visits (0.64 (0.36) vs 0.70 (0.36), p =0.001). Significant hazard ratio for change in SE in patients with higher age (>9 years), (HR [95% confidence interval (CI)], 0.71 [0.51-0.84]), greater recreational screen usage (HR [95% CI], 1.26 [1.15-1.66]), and insufficient outdoor time (HR [95% CI], 1.45 [1.35-1.67]). Conclusion: Myopia progression was accelerated during the COVID-19 pandemic. Younger age, prolonged screen use, and insufficient outdoor time contributed to increased myopia progression. However, the type of device used had no significant effect.

Maillard reaction for nucleation of polymer quantum dots from chitosan-glucose conjugate: Antagonistic for cancer and viral diseases.

Polymer dots (PDs) ingrained from biopolymers are characterized by their biocompatibility & non-toxicity to be superiorly applicable for biomedicines. The point of novelty in the current study is to focus on the effect of Maillard reaction for conjugation of chitosan with glucose to enhance the affinity of chitosan as a biological resource of PDs. Chitosan-glucose conjugate was firstly prepared by Maillard reaction. PDs were nucleated from chitosan (C1 acidic, 10.6 nm & C2 basic, 11.4 nm) and chitosan-glucose conjugate (C3 acidic, 6.8 nm & C4 basic, 5.7 nm). The affinity of chitosan versus chitosan-glucose conjugate as molecular precursors for PDs as antiviral and anticancer laborers was studied. The synthesized PDs were tested against lung cancer (NSCLC, A549) and the estimated IC50 was 282.4 & 165.4 µg/mL for PDs (C3 & C4) ingrained from chitosan-glucose conjugate. The antiviral action of PDs against Coronavirus (229E) was estimated and the obtained IC50 for C3 & C4 was 43.6 and 19.3 mg/mL, respectively. PDs ingrained from chitosan-glucose conjugate showed higher anticancer and antiviral activities compared to that clustered from chitosan. Consequently, the modification of chitosan via Maillard reaction enhanced the biological affinity of the obtained PDs to be effectively applicable as antitumor and antiviral laborers.

Ischemic cardiomyopathy versus non-ischemic cardiomyopathy in diabetic patients: clinical characteristics, management, and long-term outcomes.

BACKGROUND: Diabetes mellitus causes ischemic heart disease (IHD) through macrovascular or microvascular involvement. Diabetes-associated hypertension, dyslipidemia, and obesity further increase coronary artery disease risk and can cause left ventricular hypertrophy leading to heart failure with preserved ejection fraction independent of IHD. This study was undertaken to evaluate the differences in demographics, clinical characteristics, Echocardiographic parameters, management, and outcomes between non-ischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) patients in cohort of diabetes patients. METHODS: This retrospective study included diabetes patients with reduced ejection fraction (≤40) who were hospitalized with heart failure between January 2014 and February 2020. Patients were divided into two groups: group 1; ICM and group 2; NICM. Data obtained on above mentioned features including mortality and heart failure readmissions were compared between the two groups. RESULTS: A total of 612 diabetes patients admitted with acute heart failure were screened of which 442 were included. Group 1 (ICM) had 361 patients (81.7%) and group 2 (NICM) had 81 patients (18.3%). Patients in group 1 were older, predominantly males and with higher prevalence of hypertension, smoking and insulin dependent Diabetes while group 2 patients had higher BMI and higher prevalence of cardiac rhythm problems. No significant difference was detected in 5-year-mortality between the two groups (P=0.165). However, heart failure associated hospitalizations were higher in group 2 though it was not statistically significant (P=0.062). CONCLUSION: There was no difference in 5-years mortality between ICM and NICM in diabetes patients. However, NICM patients had higher prevalence of obesity and rhythm problems.

The Safety and Efficacy of Low-Molecular-Weight Heparin in Pregnant Women With Rheumatic Heart Disease and Valves Replacement.

BACKGROUND: In patients with rheumatic heart disease (RHD) and prosthetic valve replacement, the risk of thromboembolic complications is the highest during and immediately after pregnancy. Therapeutic anticoagulation during this period is crucial to minimize the risk of thromboembolic complications. The use of low-molecular-weight heparin (LMWH) remains an off-label indication. The type of anticoagulants used, dosing regimens, target anti-Xa levels, and frequency of anti-Xa monitoring are highly variable in the pregnant population and have been derived from pilots, observational studies, and empirical evidence. Herein, in a real-world setting, we sought to examine the efficacy and safety of variable anticoagulation options with a focus on LMWH in the management of RHD-related valvular disease in pregnant women. METHODS: This study is a retrospective study conducted at a large university-affiliated tertiary care center (King Saud University Medical City) between January 2011 and February 2020. All pregnant women with RHD who had heart valve replacements were reviewed. Patient data were extracted for demographic information, baseline characteristics, anticoagulation type, and primary outcomes. Primary endpoints were thromboembolic events, hemorrhagic complications, and fetal outcomes. RESULTS: A total of 744 pregnancies in 149 women were identified. The mean age ± SD of the women was 43.8 ± 12 years. A total of 86 women (58%) were on the LMWH regimen, 35 women (23%) were on LMWH and warfarin regimen, and 28 women (19%) were on unfractionated heparin (UFH) and warfarin regimen. Overall, thromboembolic events developed in five (0.7%) pregnancies. Of those, two were in the LMWH group, two were in the LMWH and warfarin group, and one was in the UFH and warfarin group. In addition, significant hemorrhagic complications occurred in five pregnancies. Of these, two occurred in the LMWH group, two in the LMWH and warfarin group, and one in the UFH and warfarin group. No adverse maternal and fetal outcomes were noted. CONCLUSION: This study presents the largest retrospective study of variable anticoagulation options in pregnant women with RHD and prosthetic valve replacement. LMWH is both safe and effective in preventing major thromboembolic complications compared to other forms of anticoagulation used during pregnancy.

Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth.

PURPOSE: Tumor relapse after radiotherapy is a major hurdle in treating pediatric H3K27M-mutant diffuse midline gliomas (DMG). Radiotherapy-induced stress increases association of BCL2 family of proteins with BH3 pro-apoptotic activators preventing apoptosis. We hypothesized that inhibition of radiotherapy-induced BCL2 with a clinically relevant inhibitor, venetoclax, will block BCL2 activity leading to increased apoptosis. BCL2 has never been implicated in DMG as a radiotherapy-induced resistant mechanism. EXPERIMENTAL DESIGN: We performed an integrated genomic analysis to determine genes responsible for radioresistance and a targeted drug screen to identify drugs that synergize with radiation in DMG. Effect of venetoclax on radiation-naïve and 6 Gy radiation on cells was evaluated by studying cell death, changes in BCL2 phosphorylation, reactive oxygen species (ROS), and apoptosis, as well as BCL2 association with BH3 apoptosis initiators. The efficacy of combining venetoclax with radiation was evaluated in vivo using orthotopic xenograft models. RESULTS: BCL2 was identified as a key regulator of tumor growth after radiation in DMGs. Radiation sensitizes DMGs to venetoclax treatment independent of p53 status. Venetoclax as a monotherapy was not cytotoxic to DMG cells. Postradiation venetoclax treatment significantly increased cell death, reduced BCL2-BIM association, and augmented mitochondrial ROS leading to increased apoptosis. Combining venetoclax with radiotherapy significantly enhanced the survival of mice with DMG tumors. CONCLUSIONS: This study shows that venetoclax impedes the antiapoptotic function of radiation-induced BCL2 in DMG, leading to increased apoptosis. Results from these preclinical studies demonstrate the potential use of the BCL2 inhibitor venetoclax combined with radiotherapy for pediatric DMG.

Affinity of carbon quantum dots anchored within metal organic framework matrix as enhancer of plant nourishment.

Nano-fertilizers were ascribed to be significantly advantageous with minimizing the negative effects of requiring excessive contents in the soil and reducing the number of times for fertilization. Herein, the superior affinity of carbon quantum dots (CQDs) anchored within metal organic framework (Cu-BTC) matrix was investigated for the first time as a fertilizer for sunflower. CQDs were nucleated from alkali-hydrolyzed carboxymethyl cellulose (CMC) via the hydrothermal technique. The synthesized CQDs (6.8 ± 3.7 nm) were anchored within Cu-BTC (crystalline rod-like structure) matrix, to produce CQDs@Cu-BTC composite. The obtained CQDs and CQDs@Cu-BTC were applied as nutrients for the sunflower plant. The chlorophyll a and carotenoids contents were 0.465 & 0.497 and 0.350 & 0.364 mg/g after treatment with CQDs & CQDs@Cu-BTC, respectively. The shoot length of sunflower sample was increased after feeding with CQDs and CQDs@Cu-BTC to be 38.7 and 46.5 cm, respectively. The obtained results confirmed that, the synthesized CQDs@Cu-BTC showed superiority as nutrient material via enhancing the growth and physiological properties of sunflower and consequently could be used as fertilizer for plants instead of the commercial nutrient.

Hemostatic profile detailing in apparent VWD cases: A cross sectional study.

The von willebrand disease (vWD) accounts to be one of the most common hereditary bleeding ailment that amounts its incidence to almost 1.5% of normal population. It is mostly associated with a defect in primary hemostasis as well as secondary defect in coagulation factor VIII as diagnosis of vwd happened to be challenging with earlier diagnostic criteria's. Testing Vwd in menorrhagia patients was not at ease. A cross-sectional study was conducted in female patients who have visited obstetrics and gynecology clinic at King Saud University Medical City (KSUMC), Riyadh, Saudi Arabia. The inclusion criteria consist of adult female patients between 16 and 45 years old with menorrhagia. A sample of 45 patients were screened and selected for the above-mentioned study. The SPSS Statistical analysis package was performed to analyze the data's. The fisher's exact test was conducted to compare the demographic variables. The independent samples t-test was conducted to compare the means of subjects. The P value of ≤0.05 considered as statistically significant. The cases manifested with a history of bleeding during periods stretching from 7 to 90 days. The vWD was reported in 6.6 % (n = 3) women out of the total 45 patients. The vWF: Ac mean ± SD (51.4 ± 6.3) and vWF: Ag Mean ± SD (93 ± 67) were significantly lesser in vWD patients with that of non-vWD (98.7 ± 22.6) vs (116 ± 42.4) (p = 0.027) (p = 0.032) respectively. WBC, ESR, MCV, MCH, Hemoglobin, PLT count, INR, PT, APTT and FVIII showed no significant difference among the groups (p > 0.05).