iScience. 2023 Apr 25;26(5):106746. doi: 10.1016/j.isci.2023.106746. eCollection 2023 May 19.

ABSTRACT

The tumor, nodes and metastasis (TNM) classification system provides useful but incomplete prognostic information and lacks the assessment of the tumor microenvironment (TME). Collagen, the main component of the TME extracellular matrix, plays a nonnegligible role in tumor invasion and metastasis. In this cohort study, we aimed to develop and validate a TME collagen signature (CSTME) for prognostic prediction of stage II/III colorectal cancer (CRC) and to compare the prognostic values of "TNM stage + CSTME" with that of TNM stage alone. Results indicated that the CSTME was an independent prognostic risk factor for stage II/III CRC (hazard ratio: 2.939, 95% CI: 2.180-3.962, p < 0.0001), and the integration of the TNM stage and CSTME had a better prognostic value than that of the TNM stage alone (AUC(TNM+CSTME) = 0.772, AUC TNM = 0.687, p < 0.0001). This study provided an application of "seed and soil" strategy for prognosis prediction and individualized therapy.

PMID:37216096 | PMC:PMC10192940 | DOI:10.1016/j.isci.2023.106746

Front Pediatr. 2023 May 4;11:1163100. doi: 10.3389/fped.2023.1163100. eCollection 2023.

ABSTRACT

Animal models provide useful information on mechanisms in human disease conditions, but also on exploring (patho)physiological factors affecting pharmacokinetics, safety, and efficacy of drugs in development. Also, in pediatric patients, nonclinical data can be critical for better understanding the disease conditions and developing new drug therapies in this age category. For perinatal asphyxia (PA), a condition defined by oxygen deprivation in the perinatal period and possibly resulting in hypoxic ischemic encephalopathy (HIE) or even death, therapeutic hypothermia (TH) together with symptomatic drug therapy, is the standard approach to reduce death and permanent brain damage in these patients. The impact of the systemic hypoxia during PA and/or TH on drug disposition is largely unknown and an animal model can provide useful information on these covariates that cannot be assessed separately in patients. The conventional pig is proven to be a good translational model for PA, but pharmaceutical companies do not use it to develop new drug therapies. As the Göttingen Minipig is the commonly used pig strain in nonclinical drug development, the aim of this project was to develop this animal model for dose precision in PA. This experiment consisted of the instrumentation of 24 healthy male Göttingen Minipigs, within 24 h of partus, weighing approximately 600 g, to allow the mechanical ventilation and the multiple vascular catheters inserted for maintenance infusion, drug administration and blood sampling. After premedication and induction of anesthesia, an experimental protocol of hypoxia was performed, by decreasing the inspiratory oxygen fraction (FiO2) at 15%, using nitrogen gas. Blood gas analysis was used as an essential tool to evaluate oxygenation and to determine the duration of the systemic hypoxic insult to approximately 1 h. The human clinical situation was mimicked for the first 24 h after birth in case of PA, by administering four compounds (midazolam, phenobarbital, topiramate and fentanyl), frequently used in a neonatal intensive care unit (NICU). This project aimed to develop the first neonatal Göttingen Minipig model for dose precision in PA, allowing to separately study the effect of systemic hypoxia versus TH on drug disposition. Furthermore, this study showed that several techniques that were thought to be challenging or even impossible in these very small animals, such as endotracheal intubation and catheterization of several veins, are feasible by trained personnel. This is relevant information for laboratories using the neonatal Göttingen Minipig for other disease conditions or drug safety testing.

PMID:37215599 | PMC:PMC10195037 | DOI:10.3389/fped.2023.1163100

Alzheimers Dement (N Y). 2023 May 17;9(2):e12394. doi: 10.1002/trc2.12394. eCollection 2023 Apr-Jun.

ABSTRACT

Alzheimer's disease (AD) drug discovery has focused on a set of highly studied therapeutic hypotheses, with limited success. The heterogeneous nature of AD processes suggests that a more diverse, systems-integrated strategy may identify new therapeutic hypotheses. Although many target hypotheses have arisen from systems-level modeling of human disease, in practice and for many reasons, it has proven challenging to translate them into drug discovery pipelines. First, many hypotheses implicate protein targets and/or biological mechanisms that are under-studied, meaning there is a paucity of evidence to inform experimental strategies as well as high-quality reagents to perform them. Second, systems-level targets are predicted to act in concert, requiring adaptations in how we characterize new drug targets. Here we posit that the development and open distribution of high-quality experimental reagents and informatic outputs-termed target enabling packages (TEPs)-will catalyze rapid evaluation of emerging systems-integrated targets in AD by enabling parallel, independent, and unencumbered research.

PMID:37215505 | PMC:PMC10192886 | DOI:10.1002/trc2.12394

Front Pharmacol. 2023 May 5;14:1087850. doi: 10.3389/fphar.2023.1087850. eCollection 2023.

ABSTRACT

Acute respiratory viral infections (ARVI) are the most common illnesses worldwide. In some instances, mild cases of ARVI progress to hyperinflammatory responses, which are damaging to pulmonary tissue and requiring intensive care. Here we summarize available information on preclinical and clinical effects of XC221GI (1-[2-(1-methyl imidazole-4-yl)-ethyl]perhydroazin-2,6-dione), an oral drug with a favorable safety profile that has been tested in animal models of influenza, respiratory syncytial virus, highly pathogenic coronavirus strains and other acute viral upper respiratory infections. XC221GI is capable of controlling IFN-gamma-driven inflammation as it is evident from the suppression of the production of soluble cytokines and chemokines, including IL-6, IL-8, CXCL10, CXCL9 and CXCL11 as well as a decrease in migration of neutrophils into the pulmonary tissue. An excellent safety profile of XC221GI, which is not metabolized by the liver, and its significant anti-inflammatory effects indicate utility of this compound in abating conversion of ambulatory cases of respiratory infections into the cases with aggravated presentation that require hospitalization. This drug is especially useful when rapid molecular assays determining viral species are impractical, or when direct antiviral drugs are not available. Moreover, XC221GI may be combined with direct antiviral drugs to enhance their therapeutic effects.

PMID:37214455 | PMC:PMC10196389 | DOI:10.3389/fphar.2023.1087850

Front Mol Biosci. 2023 May 5;10:1209844. doi: 10.3389/fmolb.2023.1209844. eCollection 2023.

NO ABSTRACT

PMID:37214341 | PMC:PMC10196617 | DOI:10.3389/fmolb.2023.1209844

Front Endocrinol (Lausanne). 2023 May 5;14:1180254. doi: 10.3389/fendo.2023.1180254. eCollection 2023.

NO ABSTRACT

PMID:37214239 | PMC:PMC10196622 | DOI:10.3389/fendo.2023.1180254

Nat Rev Methods Primers. 2022;2(1):9. doi: 10.1038/s43586-022-00098-7. Epub 2022 Feb 10.

ABSTRACT

CRISPR screens are a powerful source of biological discovery, enabling the unbiased interrogation of gene function in a wide range of applications and species. In pooled CRISPR screens, various genetically encoded perturbations are introduced into pools of cells. The targeted cells proliferate under a biological challenge such as cell competition, drug treatment or viral infection. Subsequently, the perturbation-induced effects are evaluated by sequencing-based counting of the guide RNAs that specify each perturbation. The typical results of such screens are ranked lists of genes that confer sensitivity or resistance to the biological challenge of interest. Contributing to the broad utility of CRISPR screens, adaptations of the core CRISPR technology make it possible to activate, silence or otherwise manipulate the target genes. Moreover, high-content read-outs such as single-cell RNA sequencing and spatial imaging help characterize screened cells with unprecedented detail. Dedicated software tools facilitate bioinformatic analysis and enhance reproducibility. CRISPR screening has unravelled various molecular mechanisms in basic biology, medical genetics, cancer research, immunology, infectious diseases, microbiology and other fields. This Primer describes the basic and advanced concepts of CRISPR screening and its application as a flexible and reliable method for biological discovery, biomedical research and drug development - with a special emphasis on high-content methods that make it possible to obtain detailed biological insights directly as part of the screen.

PMID:37214176 | PMC:PMC10200264 | DOI:10.1038/s43586-022-00098-7

Interface Focus. 2023 Apr 14;13(3):20230009. doi: 10.1098/rsfs.2023.0009. eCollection 2023 Jun 6.

ABSTRACT

We present a scenario for the origin of biological coding, a semiotic relationship between chemical information stored in one location that links to chemical information stored in a separate location. Coding originated from cooperation between two, originally separate, collectively autocatalytic sets (CASs), one for nucleic acids and one for peptides. Upon interaction, a series of RNA folding-directed processes led to their joint cooperativity. The aminoacyl adenylate was the first covalent association made by these two CASs and solidified their interdependence, and is a palimpsest of this era, a relic of the original semiotic relationship between RNA and proteins. Coding was driven by selection pressure to eliminate waste in CASs. Eventually a 1 : 1 relationship between single amino acids and short RNA pieces was established, i.e. the 'genetic code'. The two classes of aaRS enzymes are remnants of the complementary information in two RNA strands, as postulated by Rodin and Ohno. Every stage in the evolution of coding was driven by the downward selection on the components of a system to satisfy the Kantian whole. Coding was engendered because there were two chemically distinct classes of polymers needed for open-ended evolution; systems with only one polymer cannot exhibit this characteristic. Coding is thus synonymous with life as we know it.

PMID:37213924 | PMC:PMC10198252 | DOI:10.1098/rsfs.2023.0009

Hortic Res. 2023 Apr 4;10(5):uhad061. doi: 10.1093/hr/uhad061. eCollection 2023 May.

ABSTRACT

Grapevine is one of the most economically important crops worldwide. However, the previous versions of the grapevine reference genome tipically consist of thousands of fragments with missing centromeres and telomeres, limiting the accessibility of the repetitive sequences, the centromeric and telomeric regions, and the study of inheritance of important agronomic traits in these regions. Here, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the cultivar PN40024 using PacBio HiFi long reads. The T2T reference genome (PN_T2T) is 69 Mb longer with 9018 more genes identified than the 12X.v0 version. We annotated 67% repetitive sequences, 19 centromeres and 36 telomeres, and incorporated gene annotations of previous versions into the PN_T2T assembly. We detected a total of 377 gene clusters, which showed associations with complex traits, such as aroma and disease resistance. Even though PN40024 derives from nine generations of selfing, we still found nine genomic hotspots of heterozygous sites associated with biological processes, such as the oxidation-reduction process and protein phosphorylation. The fully annotated complete reference genome therefore constitutes an important resource for grapevine genetic studies and breeding programs.

PMID:37213686 | PMC:PMC10199708 | DOI:10.1093/hr/uhad061

Front Microbiol. 2023 May 5;14:1154815. doi: 10.3389/fmicb.2023.1154815. eCollection 2023.

ABSTRACT

A major challenge in microbial ecology is to understand the principles and processes by which microbes associate and interact in community assemblages. Microbial communities in mountain glaciers are unique as first colonizers and nutrient enrichment drivers for downstream ecosystems. However, mountain glaciers have been distinctively sensitive to climate perturbations and have suffered a severe retreat over the past 40 years, compelling us to understand glacier ecosystems before their disappearance. This is the first study in an Andean glacier in Ecuador offering insights into the relationship of physicochemical variables and altitude on the diversity and structure of bacterial communities. Our study covered extreme Andean altitudes at the Cayambe Volcanic Complex, from 4,783 to 5,583 masl. Glacier soil and ice samples were used as the source for 16S rRNA gene amplicon libraries. We found (1) effects of altitude on diversity and community structure, (2) the presence of few significantly correlated nutrients to community structure, (3) sharp differences between glacier soil and glacier ice in diversity and community structure, where, as quantified by the Shannon γ-diversity distribution, the meta-community in glacier soil showed more diversity than in glacier ice; this pattern was related to the higher variability of the physicochemical distribution of variables in the former substrate, and (4) significantly abundant genera associated with either high or low altitudes that could serve as biomarkers for studies on climate change. Our results provide the first assessment of these unexplored communities, before their potential disappearance due to glacier retreat and climate change.

PMID:37213502 | PMC:PMC10196084 | DOI:10.3389/fmicb.2023.1154815

iScience. 2023 May 3;26(6):106795. doi: 10.1016/j.isci.2023.106795. eCollection 2023 Jun 16.

ABSTRACT

Runt-related transcription factor 1 (RUNX1) is oncogenic in diverse types of leukemia and epithelial cancers where its expression is associated with poor prognosis. Current models suggest that RUNX1 cooperates with other oncogenic factors (e.g., NOTCH1, TAL1) to drive the expression of proto-oncogenes in T cell acute lymphoblastic leukemia (T-ALL) but the molecular mechanisms controlled by RUNX1 and its cooperation with other factors remain unclear. Integrative chromatin and transcriptional analysis following inhibition of RUNX1 and NOTCH1 revealed a surprisingly widespread role of RUNX1 in the establishment of global H3K27ac levels and that RUNX1 is required by NOTCH1 for cooperative transcription activation of key NOTCH1 target genes including MYC, DTX1, HES4, IL7R, and NOTCH3. Super-enhancers were preferentially sensitive to RUNX1 knockdown and RUNX1-dependent super-enhancers were disrupted following the treatment of a pan-BET inhibitor, I-BET151.

PMID:37213235 | PMC:PMC10199266 | DOI:10.1016/j.isci.2023.106795

iScience. 2023 Apr 27;26(6):106754. doi: 10.1016/j.isci.2023.106754. eCollection 2023 Jun 16.

ABSTRACT

Hepatocellular carcinoma (HCC) is highly heterogeneous, and stemness signatures are frequently elevated in HCC tumor cells to generate heterogeneous subtypes via multidirectional differentiation. However, the mechanisms affecting the regulation of stemness in HCC remain unclear. In this study, we identified that lysosome-associated protein transmembrane-4β (LAPTM4B) was significantly overexpressed in stem-like tumor cell populations with multidirectional differentiation potential at the single cell level, and verified that LAPTM4B was closely related to stemness of HCC using in vitro and in vivo experiments. Mechanistically, elevated LAPTM4B suppresses Yes-associated protein (YAP) phosphorylation and ubiquitination degradation. In turn, stabilized YAP localizes to the nucleus and binds to cAMP responsive element binding protein-1 (CREB1), which promotes transcription of LAPTM4B. Overall, our findings suggest that LAPTM4B forms a positive feedback loop with YAP, which maintains the stemness of HCC tumor cells and leads to an unfavorable prognosis for HCC patients.

PMID:37213231 | PMC:PMC10197148 | DOI:10.1016/j.isci.2023.106754

Methods Mol Biol. 2023;2655:57-66. doi: 10.1007/978-1-0716-3143-0_5.

ABSTRACT

Human chromosomes have a complex 3D spatial organization in the cell nucleus, which comprises a hierarchy of physical interactions across genomic scales. Such an architecture serves important functional roles, as genes and their regulators have to physically interact to control gene regulation. However, the molecular mechanisms underlying the formation of those contacts remain poorly understood. Here, we describe a polymer-physics-based approach to investigate the machinery shaping genome folding and function. In silico model predictions on DNA single-molecule 3D structures are validated against independent super-resolution single-cell microscopy data, supporting a scenario whereby chromosome architecture is controlled by thermodynamics mechanisms of phase separation. Finally, as an application of our methods, the validated single-polymer conformations of the theory are used to benchmark powerful technologies to probe genome structure, such as Hi-C, SPRITE, and GAM.

PMID:37212988 | DOI:10.1007/978-1-0716-3143-0_5

Microbiol Spectr. 2023 May 22:e0098723. doi: 10.1128/spectrum.00987-23. Online ahead of print.

ABSTRACT

Shiga toxin-producing Escherichia coli (STEC) can give rise to a range of clinical outcomes from diarrhea to the life-threatening systemic condition hemolytic-uremic syndrome (HUS). Although STEC O157:H7 is the serotype most frequently associated with HUS, a major outbreak of HUS occurred in 2011 in Germany and was caused by a rare serotype, STEC O104:H4. Prior to 2011 and since the outbreak, STEC O104:H4 strains have only rarely been associated with human infections. From 2012 to 2020, intensified STEC surveillance was performed in Germany where the subtyping of ~8,000 clinical isolates by molecular methods, including whole-genome sequencing, was carried out. A rare STEC serotype, O181:H4, associated with HUS was identified, and like the STEC O104:H4 outbreak strain, this strain belongs to sequence type 678 (ST678). Genomic and virulence comparisons revealed that the two strains are phylogenetically related and differ principally in the gene cluster encoding their respective lipopolysaccharide O-antigens but exhibit similar virulence phenotypes. In addition, five other serotypes belonging to ST678 from human clinical infection, such as OX13:H4, O127:H4, OgN-RKI9:H4, O131:H4, and O69:H4, were identified from diverse locations worldwide. IMPORTANCE Our data suggest that the high-virulence ensemble of the STEC O104:H4 outbreak strain remains a global threat because genomically similar strains cause disease worldwide but that the horizontal acquisition of O-antigen gene clusters has diversified the O-antigens of strains belonging to ST678. Thus, the identification of these highly pathogenic strains is masked by diverse and rare O-antigens, thereby confounding the interpretation of their potential risk.

PMID:37212677 | DOI:10.1128/spectrum.00987-23

Microbiol Spectr. 2023 May 22:e0037323. doi: 10.1128/spectrum.00373-23. Online ahead of print.

ABSTRACT

The pGinger suite of expression plasmids comprises 43 plasmids that will enable precise constitutive and inducible gene expression in a wide range of Gram-negative bacterial species. Constitutive vectors are composed of 16 synthetic constitutive promoters upstream of red fluorescent protein (RFP), with a broad-host-range BBR1 origin and a kanamycin resistance marker. The family also has seven inducible systems (Jungle Express, Psal/NahR, Pm/XylS, Prha/RhaS, LacO1/LacI, LacUV5/LacI, and Ptet/TetR) controlling RFP expression on BBR1/kanamycin plasmid backbones. For four of these inducible systems (Jungle Express, Psal/NahR, LacO1/LacI, and Ptet/TetR), we created variants that utilize the RK2 origin and spectinomycin or gentamicin selection. Relevant RFP expression and growth data have been collected in the model bacterium Escherichia coli as well as Pseudomonas putida. All pGinger vectors are available via the Joint BioEnergy Institute (JBEI) Public Registry. IMPORTANCE Metabolic engineering and synthetic biology are predicated on the precise control of gene expression. As synthetic biology expands beyond model organisms, more tools will be required that function robustly in a wide range of bacterial hosts. The pGinger family of plasmids constitutes 43 plasmids that will enable both constitutive and inducible gene expression in a wide range of nonmodel Proteobacteria.

PMID:37212656 | DOI:10.1128/spectrum.00373-23

J Vis Exp. 2023 May 5;(195). doi: 10.3791/65285.

ABSTRACT

Transgenerational epigenetic inheritance (TEI) allows the transmission of information through the germline without changing the genome sequence, through factors such as non-coding RNAs and chromatin modifications. The phenomenon of RNA interference (RNAi) inheritance in the nematode Caenorhabditis elegans is an effective model to investigate TEI that takes advantage of this model organism's short life cycle, self-propagation, and transparency. In RNAi inheritance, exposure of animals to RNAi leads to gene silencing and altered chromatin signatures at the target locus that persist for multiple generations in the absence of the initial trigger. This protocol describes the analysis of RNAi inheritance in C. elegans using a germline-expressed nuclear green fluorescent protein (GFP) reporter. Reporter silencing is initiated by feeding the animals bacteria expressing double-stranded RNA targeting GFP. At each generation, animals are passaged to maintain synchronized development, and reporter gene silencing is determined by microscopy. At select generations, populations are collected and processed for chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction (qPCR) to measure histone modification enrichment at the GFP reporter locus. This protocol for studying RNAi inheritance can be easily modified and combined with other analyses to further investigate TEI factors in small RNA and chromatin pathways.

PMID:37212594 | DOI:10.3791/65285

Sheng Wu Gong Cheng Xue Bao. 2023 May 25;39(5):2053-2069. doi: 10.13345/j.cjb.230033.

ABSTRACT

In recent years, the petroleum-based plastic pollution problem has been causing global attention. The idea of "degradation and up-cycling of plastics" was proposed for solving the environmental pollution caused by non-degradable plastics. Following this idea, plastics would be firstly degraded and then reconstructed. Polyhydroxyalkanoates (PHA) can be produced from the degraded plastic monomers as a choice to recycle among various plastics. PHA, a family of biopolyesters synthesized by many microbes, have attracted great interest in industrial, agricultural and medical sectors due to its biodegradability, biocompatibility, thermoplasticity and carbon neutrality. Moreover, the regulations on PHA monomer compositions, processing technology, and modification methods may further improve the material properties, making PHA a promising alternative to traditional plastics. Furthermore, the application of the "next-generation industrial biotechnology (NGIB)" utilizing extremophiles for PHA production is expected to enhance the PHA market competitiveness, promoting this environmentally friendly bio-based material to partially replace petroleum-based products, and achieve sustainable development with carbon-neutrality. This review summarizes the basic material properties, plastic upcycling via PHA biosynthesis, processing and modification methods of PHA, and biosynthesis of novel PHA.

PMID:37212231 | DOI:10.13345/j.cjb.230033

Mol Ecol. 2023 Jun;32(11):2692-2694. doi: 10.1111/mec.16971. Epub 2023 Apr 30.

ABSTRACT

In aquatic ecosystems, marine and freshwater environments are separated by steep salinity gradients. The osmotic stress induced by this 'invisible wall' forms an insurmountable barrier for many aquatic lifeforms, including bacteria, algae and animals. Because the osmotic differences when transiting a salinity divide are so hard to overcome, most species have adapted exclusively to a marine or a freshwater lifestyle. A major consequence of this physiological specialization into marine and freshwater organisms is that transitions are relatively rare, impeding regular contact and colonization. While some animals use specialized organs or behaviour to cope with unfavourable salinity levels, unicellular algae such as diatoms are completely dependent on cellular mechanisms to mitigate salinity stress. In this issue of Molecular Ecology, Downey and colleagues investigate the transcriptomic response of a salinity-tolerant diatom to a shock treatment with freshwater (Molecular Ecology, 2023). Through frequent sampling and integration of existing RNA sequencing data, a fine-grained model of the acclimation to hypo-osmotic stress emerges. Deciphering the pathways that drive the acute and long-term acclimation to freshwater has major implications for diatom ecology, diversification and resilience to global change.

PMID:37212189 | DOI:10.1111/mec.16971

Epigenomics. 2023 May 22. doi: 10.2217/epi-2023-0078. Online ahead of print.

ABSTRACT

Nicotinamide metabolism is important in carcinogenesis. Nicotinamide affects the cellular methyl pool, thus affecting DNA and histone methylation and gene expression. Cancer cells have increased expression of nicotinamide N-methyl transferase (NNMT), the key enzyme in nicotinamide metabolism. NNMT contributes to tumor angiogenesis. Overexpression of NNMT is associated with poorer prognosis in cancers. Additionally, NNMT can contribute to cancer-associated morbidities, such as cancer-associated thrombosis. 1-methylnicotinamide (1-MNA), a metabolite of nicotinamide, has anti-inflammatory and antithrombotic effects. Therefore, targeting NNMT can affect both carcinogenesis and cancer-associated morbidities. Several antitumor drugs have been shown to inhibit NNMT expression in cancer cells. Implementing these drugs to reverse NNMT effects in addition to 1-MNA supplementation has the potential to prevent cancer-associated thrombosis through various mechanisms.

PMID:37212051 | DOI:10.2217/epi-2023-0078

Cell J. 2023 Apr 1;25(4):217-221. doi: 10.22074/cellj.2022.8165.

ABSTRACT

OBJECTIVE: Recent studies imply extensive applications for the human amniotic membrane (hAM) and its extract in medicine and ophthalmology. The content of hAM meets many requirements in eye surgeries, such as refractive surgery as the most important and commonly used method for treating the dramatically increasing refractive errors. However, they are associated with complications such as corneal haziness and corneal ulcer. This study was designed to evaluate the impact of amniotic membrane extracted eye drop (AMEED) on Trans-PRK surgery complications.

MATERIALS AND METHODS: This randomized controlled trial was performed during two years (July 1, 2019-September 1, 2020). Thirty-two patients (64 eyes), including 17 females and 15 males, aged 20 to 50 years (mean age of 29.59 ± 6.51) with spherical equivalent between -5 to -1.5 underwent Trans Epithelial Photorefractive Keratectomy (Trans-PRK) surgery. One eye was selected per case (case group) and the other eye was considered as control. Randomization was done using the random allocation rule. The case group was treated with AMEED, and the artificial tear drop every 4 hours. The control eyes received artificial tear drops instilled every 4 hours. The evaluation continued for three days after the Trans-PRK surgery.

RESULTS: A significant decrease in CED size was found in the AMEED group on the second day after surgery (P=0.046). Also, this group had a substantial reduction in pain, hyperemia, and haziness.

CONCLUSION: This study showed that AMEED drop can increase the healing rate of corneal epithelial lesions after Trans- PRK surgery and reduce the early and late complications of Trans-PRK surgery. Researchers and Ophthalmologists should consider AMEED as a selection in patients with persistent corneal epithelial defects and patients who have difficulty in corneal epithelial healing. We understood AMEED has a different effect on the cornea after surgery; therefore, the researcher must know AMEED's exact ingredients and help expand AMEED uses (registration number: TCTR20230306001).

PMID:37210641 | DOI:10.22074/cellj.2022.8165