Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. METHODS: A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. RESULTS: After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. CONCLUSION: Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Interaction of gyrotactic moment of microorganisms and nanoparticles for magnetized and chemically reactive shear-thinning fluid with stratification phenomenon.

Nanotechnology has gained substantial attention on account of its vast applications in food manufacturing, heat exchanges, electronic cooling systems, medical treatment, coolant processes, energy production, biotechnology, transportation, biochemistry, nuclear reactors, and metrology. Currently, the phenomenon of bioconvection using nanomaterials has found wide industrial and technical implementations. Contemporary nanofluids are a dynamic source for illuminating heat transport systems related to engineering as well as industrial phenomena. Bioconvection has numerous applications in bio-micro-systems, owing to the augmentation in mass renovation besides collaborating, which are vital complications in diverse micro-systems. This study intended to model and examine an incompressible, unsteady 3D Casson fluid nanofluid with bioconvection on a stretching surface. A model by means of these characteristics is beneficial in applications, such as in nuclear reactors, coolants in automobiles, metallurgical procedures, energy construction, micro-manufacturing, industrial engineering, and geophysical fluid mechanics along with dynamics. The performance of the Brownian motion along with thermophoresis diffusion is assumed through an extraordinary effect of thermal radiation in the temperature equation of the fluid movement. This model was created by using PDE, which was then converted into an ODE system. The somatic behavior of substantial parameters was investigated graphically. Similarly, tables were interpreted to display the effect of the control of physical quantities on the local Nusselt number, local Sherwood number, and motile density. Consequently, it was determined that the temperature of Casson fluid grew exponentially with higher estimates of the magnetic parameter and the thermal Biot number. At the same time, we detected that augmented estimation of the Lewis number decreases the Casson fluid concentration. For growing values of the parameters, Biot number and the stretching parameter, there is a direct reaction for the microorganism profile.

Combined Effect of Cinnamon Bark Oil and Packaging Methods on Quality of Fresh Lamb Meat Patties during Storage at 4 °C.

The present study aimed to investigate the effects of adding cinnamon bark oil (CBO) on the quality of ground lamb meat, considering different packaging conditions, including modified atmospheric packaging (MAP) using Hengxian HX-300H and overwrapped packaging. The CBO was incorporated into lamb meat samples at three different levels: 0% (control), 0.025% and 0.05% (v/w). The samples were then subjected to three packaging methods: MAP1 (80% O2 + 20% CO2), MAP2 (40% O2 + 30% CO2 + 30% N2) and overwrapped packaging and stored at 4 °C for 0, 4, 8, 12 and 16 days. The findings of the present study revealed that the addition of 0.025% and 0.05% CBO under MAP1 condition significantly improved the color of the meat samples after 12 days of storage at 4 °C (p < 0.05). The overwrapped samples exhibited higher levels of thiobarbituric acid reactive substances (TBARS) compared to all other treatments, starting from day 4 of storage (p < 0.05). Furthermore, microbial counts were notably higher in the overwrapped samples than in all other samples after day 8 of storage (p < 0.05). In conclusion, the combination of 0.05% CBO with MAP proved to be an effective strategy for enhancing the color stability and oxidative stability of ground lamb meat. These results suggest that CBO can be utilized as a beneficial protective agent in meat packaging processes.

Dihydropyrazole Derivatives Act as Potent α-Amylase Inhibitors and Free Radical Scavengers: Synthesis, Bioactivity Evaluation, Structure-Activity Relationship, ADMET, and Molecular Docking Studies.

Dihydropyrazole (1-22) derivatives were synthesized from already synthesized chalcones. The structures of all of the synthesized compounds were confirmed by elemental analysis and various spectroscopic techniques. Furthermore, the synthesized compounds were screened against α amylase as well as investigated for antioxidant activities. The synthesized compounds demonstrate good to excellent antioxidant activities with IC50 values ranging between 30.03 and 913.58 µM. Among the 22 evaluated compounds, 11 compounds exhibit excellent activity relative to the standard ascorbic acid IC50 = 287.30 µM. Interestingly, all of the evaluated compounds show good to excellent α amylase activity with IC50 values lying in the range between 0.5509 and 810.73 µM as compared to the standard acarbose IC50 = 73.12 µM. Among the investigated compounds, five compounds demonstrate better activity compared to the standard. In order to investigate the binding interactions of the evaluated compounds with amylase protein, molecular docking studies were conducted, which show an excellent docking score as compared to the standard. Furthermore, the physiochemical properties, drug likeness, and ADMET were investigated, and it was found that none of the compounds violate Lipiniski's rule of five, which shows that this class of compounds has enough potential to be used as a drug candidate in the near future.

A novel homozygous missense substitution p.Thr313Ile in the PDE6B gene underlies autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family.

BACKGROUND: Retinitis pigmentosa (RP) is one of the most frequent hereditary retinal diseases that often starts with night blindness and eventually leads to legal blindness. Our study aimed to identify the underlying genetic cause of autosomal recessive retinitis pigmentosa (arRP) in a consanguineous Pakistani family. METHODS: Following a detailed ophthalmological examination of the patients by an ophthalmologist, whole-exome sequencing was performed on the proband's DNA to delineate the genetic cause of RP in the family. In-depth computational methods, in-silico analysis, and familial co-segregation study were performed for variant detection and validation. RESULTS: We studied an inbred Pakistani family with two siblings affected by retinitis pigmentosa. The proband, a 32 years old female, was clinically diagnosed with RP at the age of 6 years. A classical night blindness symptom was reported in the proband since her early childhood. OCT report showed a major reduction in the outer nuclear layer and the ellipsoid zone width, leading to the progression of the disease. Exome sequencing revealed a novel homozygous missense mutation (c.938C > T;p.Thr313Ile) in exon 12 of the PDE6B gene. The mutation p.Thr313Ile co-segregated with RP phenotype in the family. The altered residue (p.Thr313) was super conserved evolutionarily across different vertebrate species, and all available in silico tools classified the mutation as highly pathogenic. CONCLUSION: We present a novel homozygous pathogenic mutation in the PDE6B gene as the underlying cause of arRP in a consanguineous Pakistani family. Our findings highlight the importance of missense mutations in the PDE6B gene and expand the known mutational repertoire of PDE6B-related RP.

Exploring the role of lipoprotein(a) in cardiovascular diseases and diabetes in Chinese population.

A high level of lipoprotein (a) in the plasma has been associated with a variety of cardiovascular diseases and is considered to be an independent predictor of some other diseases. Based on recent studies, the concentration levels of Lp(a) in the Chinese population exhibit a distinctive variation from other populations. In the Chinese population, a high level of Lp(a) indicates a higher incidence of revascularization, platelet aggregation, and thrombogenicity following PCI. Increased risk of atherosclerotic cardiovascular disease (ASCVD) in Chinese population has been linked to higher levels of Lp(a), according to studies. More specifically, it has been found that in Chinese populations, higher levels of Lp(a) were linked to an increased risk of coronary heart disease, severe aortic valve stenosis, deep vein thrombosis in patients with spinal cord injuries, central vein thrombosis in patients receiving hemodialysis, and stroke. Furthermore, new and consistent data retrieved from several clinical trials also suggest that Lp (a) might also play an essential role in some other conditions, including metabolic syndrome, type 2 diabetes and cancers. This review explores the clinical and epidemiological relationships among Lp(a), cardiovascular diseases and diabetes in the Chinese population as well as potential Lp(a) underlying mechanisms in these diseases. However, further research is needed to better understand the role of Lp(a) in cardiovascular diseases and especially diabetes in the Chinese population.

Triple combination of SPR741, clarithromycin, and erythromycin against Acinetobacter baumannii and its tolerant phenotype.

AIMS: Extensively drug-resistant (XDR) Acinetobacter baumannii poses a severe threat to public health due to its ability to form biofilms and persister cells, which contributes to critical drug resistance and refractory device-associated infections. A novel strategy to alleviate such an emergency is to identify promising compounds that restore the antimicrobial susceptibility of existing antibiotics against refractory infections. METHODS AND RESULTS: Here, we found a significant synergy among three combinations of SPR741, clarithromycin and erythromycin with a potent antimicrobial activity against XDR A. baumannii (SPR741/CLA/E at 8/10/10 µg ml-1 for XDR AB1069 and at 10/16/10 µg ml-1 for XDR AB1208, respectively). Moreover, the triple combination therapy exhibits a significant antipersister and antibiofilm effect against XDR strains. Mechanistic studies demonstrate that SPR741 may promote intracellular accumulation of macrolides by permeabilizing the outer membrane as well as disrupting membrane potential and further enhance the quorum sensing inhibition activity of the macrolides against XDR A. baumannii and its biofilms. In addition, the triple combination of SPR741 with clarithromycin and erythromycin was not easy to induce resistance in A. baumannii and had effective antimicrobial activity with low toxicity in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: Collectively, these results reveal the potential of SPR741 in combination with clarithromycin and erythromycin as a clinical therapy for refractory infections caused by XDR A. baumannii.

Examining the effectiveness of information technology in sports psychology interventions: A comprehensive review / Examinar la eficacia de la tecnología de la información en las intervenciones de psicología deportiva: una revisión exhaustiva

The essential purpose of this research study is to determine the effectiveness related to information technology in sports psychology intervention. This research study depends upon primary data to determine the study and develop different questions. The informative technology is considered the independent variable, and the sport psychology intervention is the main dependent variable. I used smart PLS software to determine the research and generated informative results related to each variable, including independent and dependent. The descriptive statistic analysis, the correlation coefficient, the significant analysis, and the smart PLS algorithm model also explain the graphical analysis between them. The overall research study found that information technology directly and significantly relates to sport psychology interventions.(AU)

Research on the use of virtual playing fields for monitoring various sports / Investigación sobre el uso de campos de juego virtuales para el seguimiento de diversos deportes

The essential purpose of this research study is measure the use of virtual playing fields for monitoring various sports. This research study depends upon primary data analysis research measure the virtual playing fields related to the monitoring various sports. Research based on survey methods develops research questions related to the variables. for measuring the research study used smart PLS software and generate different results related to the variables. the R square, co-linearity statistic, total effects, significant analysis, also that smart PLS Algorithm model related to the use of virtual playing fields for monitoring various sports. Overall result founded that virtual playing felid is most important for monitoring various sport activities. Result also founded that there are positive and significant use of virtual playing fields for monitoring various sports.(AU)

Study on antibacterial effect of halicin (SU3327) against Enterococcus faecalis and Enterococcus faecium.

Enterococci are important pathogens of nosocomial infections and are increasingly difficult to treat due to their intrinsic and acquired resistance to a range of antibiotics. Therefore, there is an urgent need to develop novel antibacterial agents, while drug repurposing is a promising approach to address this issue. Our study aimed to determine the antimicrobial efficacy of halicin against enterococci and found that the minimum inhibitory concentrations (MIC) of halicin against different strains of Enterococcus faecalis and Enterococcus faecium ranged from 4 to 8 µg/ml. In addition, the synergistic antibacterial effect between halicin and doxycycline (DOX) against Enterococcus was observed through the checkerboard method, and it was observed that halicin and DOX could significantly synergistically inhibit biofilm formation and eradicate preformed biofilms at sub-MICs. Moreover, the electron microscope results revealed that halicin could also disrupt the bacterial cell membrane at high concentrations. Furthermore, it is also confirmed that the combination of halicin and DOX has no significant cytotoxic effect on erythrocytes and other human-derived cells. In addition, the mouse subcutaneous model and H&E staining showed that the combination of halicin and DOX could effectively reduce the bacterial load and inflammatory infiltration without obvious side effects. In nutshell, these results demonstrate the potential of halicin in combination with DOX as a novel therapy against infections by Enterococcus.

Changes in postmortem metabolites profile of atypical and typical DFD beef.

This study explored the changes in postmortem metabolites of atypical and typical DFD beef using UHPLC-Q-TOF/MS. The longissimus thoracis muscles were categorized into normal, atypical DFD and typical DFD groups. The L⁎, a⁎, b⁎, glycogen and lactic acid contents were lower (P < 0.05) in typical DFD than normal beef. A total of 240 compounds were significantly different among groups. Levels of glycerol-3-phosphate, d-ribose-5-phosphate, d-glucose-6-phosphate, d-fructose-6-phosphate, alpha-d-glucose-1-phosphate and dihydroxyacetone phosphate were higher in atypical DFD than those in the normal and typical DFD beef and the contents of 9 amino acids were elevated in typical DFD. KEGG analysis showed that metabolomic changes were primarily related with ATP-binding cassette transporters, metabolism of purine, central carbon, glycine, serine and threonine, biosynthesis of aminoacyl-tRNA, digestion and absorption of proteins, metabolism of amino sugar and nucleotide sugar, pyrimidine, bile secretion and galactose. In conclusion, development of atypical and typical DFD meat results in differences at level of postmortem metabolite concentrations of different metabolic pathways.

Targeting PI3K/AKT/mTOR pathway to enhance the anti-leukemia efficacy of venetoclax.

BACKGROUND: The treatment of acute myeloid leukemia (AML) is developing towards "targeted therapy", which faces challenges such as low sensitivity and drug resistance. Therefore, targeted drugs need to be used in combination with other drugs to overcome clinical problems. OBJECTIVE: AML cells and animal models were used to determine the synergistic anti-leukemic effect of Dactolisib (BEZ235) and Venetoclax (ABT199) and explore its mechanism. METHODS: In vitro experiments, we used cell counting kit-8 (CCK8), flow cytometry, real-time quantitative PCR (qPCR), and Western blot to detect the anti-leukemic effects of ABT199 and BEZ235. In vivo experiments, female nude mice were injected subcutaneously with THP-1 cells to form tumors, evaluate the combined effect of ABT199 and BEZ235 by indicators such as tumor size, tumor weight, Ki67 and cleaved-Caspase3 staining. The mice's body weight and HE staining were used to evaluate the liver injury and adverse drug reactions. RESULTS: The combination of BEZ235 and ABT199 has a synergistic effect through promoting apoptosis and inhibiting proliferation. The BEZ235 increased the drug sensitivity of ABT199 by reducing the MCL-1 protein synthesis and promoted the degradation of MCL-1 protein, which is considered as the mechanism of reversing ABT199 resistance. Furthermore, the BEZ235 and ABT199 can synergistically enhance the inhibition of PI3K/AKT/mTOR pathway. CONCLUSION: The combination of BEZ235 and ABT199 exhibits a synergistic anti-tumor effect in AML by down-regulating MCL-1 protein.

WITHDRAWN: Design and Evaluation of Floating Micro-Carriers for Effective Delivery of a Hydrophobic Drug

The article has been withdrawn at the request of the authors of the journal "Current Drug Delivery",Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

SPR741, Double- or Triple-Combined With Erythromycin and Clarithromycin, Combats Drug-Resistant Klebsiella pneumoniae, Its Biofilms, and Persister Cells.

Klebsiella pneumoniae has emerged as a major clinical and public health threat owing to the increasing prevalence of healthcare-associated infections caused by multidrug-resistant or extensively drug-resistant strains. However, increasing antibiotic resistance and the absence of clinically effective antimicrobial agents make combination therapy an urgent need. This study investigated the anti-microbial activity of SPR741, a polymyxin B derivative, in combination with macrolide antibiotics (erythromycin and clarithromycin), against extensively drug-resistant and pandrug-resistant K. pneumoniae. Monotherapy, double, and triple combination therapies were performed to identify the most effective treatment combination using in vitro checkerboard, time-killing kinetics. Furthermore, we evaluated the biofilm eradication and persister cell-killing activity of these combinations using laser confocal microscopy and colony forming unit counting. In addition, a neutropenic mouse thigh infection model was used to assess the therapeutic efficacy and toxicity of the triple antibiotic combination against pandrug-resistant K. pneumoniae in vivo. Our results suggested that SPR741 combined with macrolides exhibited strong synergistic antibacterial activity against extensively drug-resistant and pandrug-resistant K. pneumoniae. These antibiotic combinations could also effectively eradicate highly resistant bacterial biofilms and persister cells in vitro and demonstrate considerable efficacy and low toxicity in vivo. In summary, our findings indicated that SPR741, in combination with macrolide antibiotics (double or triple combination), has the potential to serve as a novel treatment option against drug-resistant K. pneumoniae -related infections.

Anti-hepatitis C virus drug simeprevir: a promising antimicrobial agent against MRSA.

Staphylococcus aureus is a major human pathogen, and the appearance of methicillin-resistant S. aureus (MRSA) renders S. aureus infections more challenging to treat. Therefore, new antimicrobial drugs are urgently needed to combat MRSA infections. Drug repurposing is an effective and feasible strategy. Here, we reported that the clinically approved anti-hepatitis C virus drug simeprevir had strong antibacterial activity against MRSA, with a minimum inhibitory concentration of 2-8 µg/mL. Simeprevir did not easily induce in vitro resistance. In addition, simeprevir significantly prevented S. aureus biofilm formation. Furthermore, simeprevir displayed limited toxicity in in vitro and in vivo assays. Moreover, simeprevir showed synergistic antimicrobial effects against both type and clinical strains of S. aureus. Simeprevir combined with gentamicin effectively reduced the bacterial burden in an MRSA-infected subcutaneous abscess mouse model. Results from a series of experiments, including membrane permeability assay, membrane potential assay, intracellular ATP level assay, and electron microscope observation, demonstrated that the action of simeprevir may be by disrupting bacterial cell membranes. Collectively, these results demonstrated the potential of simeprevir as an antimicrobial agent for the treatment of MRSA infections. KEY POINTS: • Simeprevir showed strong antibacterial activity against MRSA. • The antibacterial mechanism of simeprevir was mediated by membrane disruption and intracellular ATP depletion. • In vitro and in vivo synergistic antimicrobial efficacy between simeprevir and gentamicin was found.

A novel bactericidal small molecule, STK-35, and its derivative, STK-66, as antibacterial agents against Gram-negative pathogenic bacteria in vitro and in vivo.

Due to the increasing rate of antibiotic resistance and the emergence of persister cells of Gram-negative pathogenic bacteria, the development of new antibacterial agents is urgently needed to deal with this problem. Our results indicated that both newly identified small molecule STK-35 and its derivative STK-66 exhibited effective antibacterial properties against a variety of Gram-negative pathogens including Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. The minimal inhibitory concentrations and minimal bactericidal concentrations ranges were 0·0625-8 µg ml-1 and 0·125-16 µg ml-1 , respectively, while no haemolytic activity and mammalian cell cytotoxicity were observed. The time-killing assays showed STK-35/66 had strong bactericidal activity against Gram-negative pathogens. STK-35/66 also showed different degrees of synergistic antibacterial activity with conventional antibiotics and exhibited persister cells killing activity. Moreover, STK-35/66 effectively eradicated the pre-formed biofilms of P. aeruginosa and A. baumannii. In addition, STK-35/66 significantly increased the survival rate of E. coli infected mice and induced a decrease in bacterial load of the peritonitis model. In nutshell, these results suggested that STK-35/66 possessed antimicrobial activity against Gram-negative pathogenic bacteria in vitro and in vivo, which could be considered as potential substitutes for the treatment of Gram-negative pathogenic infections after further structure optimization.

A novel homozygous missense variant p.D339N in the PKLR gene correlates with pyruvate kinase deficiency in a Pakistani family: a case report.

BACKGROUND: Pyruvate kinase deficiency is an exceptionally rare autosomal recessive Mendelian disorder caused by bi-allelic pathogenic variants in the PKLR gene. It is mainly characterized by chronic nonspherocytic hemolytic anemia though other symptoms such as splenomegaly, hepatomegaly, pallor, fatigue, iron overload, shortness of breath, hyperbilirubinemia, and gallstones might also prevail. CASE PRESENTATION: We present here a novel genetic defect in the PKLR gene that correlates with pyruvate kinase deficiency phenotype in a consanguineous family from North-Western Pakistan. The family included three affected individuals who were all born to consanguineous parents. The proband, a 13-year-old female of Pashtun ethnicity, showed chronic nonautoimmune hemolytic anemia since birth, extremely low hemoglobin (7.6 g/dL) and pyruvate kinase (12.4 U/g Hb) levels, splenomegaly, and hepatomegaly. Bone marrow aspirate showed a markedly decreased myeloid to erythroid ratio and hypercellular marrow particles due to hyperplasia of the erythroid elements. Molecular characterization of the proband's genomic DNA uncovered a likely pathogenic homozygous missense variant p.[D339N] in exon 7 of the PKLR gene. In-depth in silico analysis and familial cosegregation implies p.[D339N] as the likely cause of pyruvate kinase deficiency in this family. Further in vitro or in vivo studies are required to validate the impact of p.[D339N] on protein structure and/or stability, and to determine its role in the disease pathophysiology. CONCLUSIONS: In summary, these findings suggest a novel genetic defect in the PKLR gene as a likely cause of pyruvate kinase deficiency, thus further expanding the mutational landscape of this rare Mendelian disorder.

Effect of Animal Age, Postmortem Calcium Chloride Marination, and Storage Time on Meat Quality Characteristics of M. longissimus thoracis et lumborum of Buffalo Bulls.

This study investigated the effect of animal age, calcium chloride marination, and storage time on meat quality characteristics of buffalo bulls to suggest a cost-effective method of improving buffalo meat quality. The current study was designed considering the importance of buffalo meat and the usage of meat from spent buffalo animals in local markets of South Asian countries. A total of 36 animals comprised of 18 young and 18 spent buffalo bulls were selected. After slaughtering and 24 h of postmortem chilling, striploins were separated and cut into 16 steaks and equally divided into two groups, i.e., either marinated with calcium chloride or not. Meat quality characteristics were recorded on 0, 2, 4, 6, 8, and 10 days of storage. The results showed that the pH value of young animals was higher than the value of spent animals and pH was increased over the storage time. Color b*, C*, and h* values were higher in spent animals as compared with the young animals; however, values of colors L* and h* were higher and a* was lower in marinated samples than the values of non-marinated samples. Color a* and C* values were increased and h* was decreased with lengthening the storage time. The meat cooking loss was higher in marinated and the water-holding capacity was higher in non-marinated meat samples. Shear force values were lower in young animals and marinated samples than the values of spent animals and non-marinated meat samples, respectively. Sensory characteristic scores of marinated samples were better than the non-marinated samples. In conclusion, calcium chloride marination can be used to improve the quality characteristics of buffalo meat.

Two-year outcomes of the MINIject drainage system for uncontrolled glaucoma from the STAR-I first-in-human trial.

BACKGROUND/AIMS: The current study evaluates the efficacy and safety of the stand-alone implantation of the MINIject (iSTAR Medical, Wavre, Belgium) supraciliary, microinvasive glaucoma drainage device in patients with medically uncontrolled open-angle glaucoma. METHODS: This prospective, multicentre, first-in-human, single-arm interventional study evaluated stand-alone, ab interno implantation in 25 patients of a 5 mm long uveoscleral device made of STAR biocompatible material, which is a soft, microporous, flexible silicone. The primary outcome was the reduction of intraocular pressure (IOP) at 6 months compared with baseline, and follow-up continued until 2 years for 21 patients. Secondary outcomes included success defined as diurnal IOP of ≤21 mmHg and >5 mmHg with an IOP reduction of 20% without (complete) or with/without (qualified) glaucoma medication. RESULTS: Mean baseline IOP was 23.2±2.9 mmHg on 2.0±1.1 glaucoma medication ingredients and decreased to 13.8±3.5 mmHg (-40.7% reduction) on 1.0±1.3 medications 2 years after implantation. Complete success was achieved in 47.6% of patients (10/21) and qualified success in 100% of patients (21/21) at the 2-year follow-up. All patients achieved a 20% IOP reduction with 48% of patients medication-free. No serious ocular adverse events or additional glaucoma surgery were reported. Mean central endothelial cell density (ECD) mildly decreased from 2411 cells/mm2 (n=26) to 2341 cells/mm2 (n=21) at 24 months, which represents a 5% decrease for matched eyes. No patient had a ≥30% decrease in central ECD. CONCLUSION: This first-in-human study on the stand-alone implantation of the MINIject supraciliary drainage system shows promising IOP-lowering results and medication reduction over 24 months with few adverse events. TRIAL REGISTRATION NUMBER: NCT03193736.

Sarcoplasmic and myofibrillar phosphoproteins profile of beef M. longissimus thoracis with different pHu at different days postmortem.

BACKGROUND: The abnormal ultimate pH (pHu ) in postmortem muscles affect the meat quality and results in substantial economic losses. Dark, firm, and dry (DFD) meat linked with the higher postmortem pHu values and exhibited many quality issues such as dark color, tough texture and shorter shelf life. This research aimed to investigate the effect of protein phosphorylation on variations in beef pHu in order to explore the possible mechanisms underlying DFD meat formation. RESULTS: Glycogen and lactate contents were higher, while L* and a* were lower in high pHu beef. Shear force was higher in intermediate pHu group. Global phosphorylation of sarcoplasmic proteins was higher in low pHu samples on day 1 and of myofibrillar proteins was higher in intermediate pHu meat on days 1 and 2 postmortem. Sarcoplasmic protein bands with different phosphorylation levels were identified as containing some glycometabolism and stress response proteins and phosphorylated myofibrillar protein bands were identified sarcomeric and metabolic proteins. CONCLUSIONS: Phosphorylation of multiple proteins of glycolytic pathway and contractile machinery may play critical roles in development of DFD beef. © 2021 Society of Chemical Industry.