Aberrant Changes Research Articles

Short term clinical observation of keratoconus treated with stromal lenticule addition keratoplasty combined with corneal collagen cross-linking

Objective: To investigate the efficacy of Femtosecond laser-assisted stromal lenticule addition keratoplasty (SLAK) combined with corneal collagen cross-linking (CXL) in the treatment of middle and advanced Keratoconus. Methods: It was a retrospective case series study. Data of 23 cases (24 eyes) of keratoconus treated with femtosecond laser-assisted SLAK combined with CXL in Laser Vision Centre of Xi'an No.1 Hospital from September 2020 to June 2022 were collected, including 16 males and 7 females, aged (23.69±5.18) years. The thickness, diopter number and diameter of the donor corneal stromal lens were assessed. uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and diopter were recorded before and 1, 3, and 6 months after surgery. Sirius 3D fault corneal topography instrument to measure flat simulated keratometry (Kf), steep simulated keratometry (Ks) and the difference between them (ΔK), as well as central corneal thickness (CCT) and corneal high-order aberration. Results: Six months after surgery, CCT (454.83±50.01) μm were significantly higher than before (384.92±35.45) μm (P<0.05). Six months after surgery, UCVA (1.41±0.32) was significantly lower than before (1.11±0.33)(P<0.05). Six months after surgery, spherical diopter [(-15.73±7.89) D], Kf [(56.82±4.76) D] and Ks [(61.00±4.70) D] were significantly higher than before [(-12.08±5.99) D, (53.55±4.95) D, (58.65±5.10) D] (P<0.05). There was no significant difference in BCVA, column mirror degree and higher order aberrations before and 6 months after surgery(P>0.05). No corneal stromal lens folds, melting and displacement were observed in all eyes during the follow-up period, and no corneal opacity or immune rejection was observed. Conclusions: femtosecond laser-assisted SLAK combined with CXL can significantly increase the corneal thickness of keratoconus and has good effectiveness. In addition, six months of postoperative follow-up of patients showed no significant changes in BCVA and high-order aberrations in the 6 mm central diameter of the cornea, and no postoperative adverse reaction were found in all eyes, indicating that the operation has certain safety.

Lead and Cadmium (Pb, Cd) Levels Determination in the Blood of the Gasoline Station Workers

The inhalation of hazardous fumes from lead containing gasoline in the workplace has become a major public health concern. These gases include extremely dangerous poisons that can induce aberrant changes in the functioning of a variety of essential organs. The current study aimed to estimate the concentration of blood lead level (BLLs) and blood cadmium level in male working gasoline station and compared with healthy people. An atomic absorption spectrophotometer (AAS) was used to measure cadmium and lead levels in the blood. The findings of this investigation revealed that there was significant increase in age (P-value = 0.002), mean age of worker station (32.0 ± 11.99) while in the control group (22.85 ± 2.18), the result of blood lead level shown (1.92 ±1.54) in gasoline station while in the control group (1.63 ±0.04) no significant differences was observed (P-value = 0.238). The main of blood cadmium level was 0.005 ±0.0069 in the gasoline station while in the control group (0.069 ±0.011) no significant differences were observed (P- value = 0.5), the smokers (n = 13) has (P &gt; 0.426) mean BLL (21.60 ± 12.88 μg/dL), while non-smoking workers (n = 8) the BLL mean was 15.52 ± 6.80 μg/dL. The results also show that there is a correlation between age and blood lead level while no correlation was observed in blood cadmium level.

Changes in relative peripheral refraction and optical quality in Chinese myopic patients after small incision lenticule extraction surgery.

To observe changes in retinal refraction difference values (RDV) and aberrations after small incision lenticule extraction (SMILE) surgery and evaluate their correlations. This study recruited 112 patients (112 eyes) who underwent SMILE for myopia. Participants were classified into the Low and Moderate Myopia group (LM, -0.50 to -6.0 D) and High Myopia group (HM, >-6.0 D) according to the central spherical equivalent (SE). RDVs in the five retinal eccentricities from 0° to 10°, 10° to 20°, 20° to 30°, 30° to 40°, and 40° to 53° are recorded as RDV-(0-10), RDV-(10-20), RDV-(20-30), RDV-(30-40), and RDV-(40-53), respectively; additionally, RDVs have four sectors, i.e., RDV-Superior (RDV-S), RDV-Inferior (RDV-I), RDV-Temporal (RDV-T), and RDV-Nasal (RDV-N). With a 3-month follow-up, changes in RDV (ΔRDV) and changes in aberrations [Δtrefoil, Δcoma, Δspherical aberration (SA), and Δtotal higher-order aberrations (HOA)] after surgery were recorded. No significant differences were observed in total RDV (TRDV), RDV-(0-53), RDV-S, RDV-I, RDV-N, trefoil, coma, and SA between the two groups before SMILE surgery. However, after SMILE, hyperopic defocus values [TRDV, RDV-(20-53), RDV-S, RDV-T, and RDV-N] in the LM group and hyperopic defocus values [TRDV, RDV-(20-53), RDV-S, and RDV-N] in the HM group were significantly lower at 3 months postoperatively than preoperatively, and the RDV-(40-53), RDV-S, and RDV-N were lower in the HM group than in the LM group. Aberrations [trefoil (vertical), coma, and HOA] in the LM group and aberrations (trefoil, coma, SA, and HOA) in the HM group were significantly higher at 3 months postoperatively than preoperatively, and the coma, trefoil(horizontal), SA, and HOA were higher in the HM group than in the LM group. In the multivariate analysis, ΔRDV-(40-53) was significantly correlated with ΔSA, and ΔRDV-T and ΔRDV-N were significantly correlated with Δcoma (horizontal). Our findings suggest that SMILE reduces retinal peripheral hyperopic defocus but introduces some higher-order aberrations, especially in people with high myopia refractive errors.

The role of oxidized non-coding RNAs of the epigenome in the development of human diseases (literature review)

The attention of scientists to the role of the epigenome in the development of human diseases is associated with the discovery of new non-coding RNA molecules of the epigenome that affect gene expression with changes in protein function and the development of diseases. The study analyzed current scientific data on the effect of oxidative stress induced by cadmium on the regulatory mechanisms of the epigenome, resulting in the development of pathological changes in the body. The results of the study showed that cadmium manifests its toxicity by oxidizing micro RNAs and long RNAs that regulate gene expression without changing DNA/histone complexes. It has been shown that epigenetic disorders under the influence of cadmium-induced oxidative stress can be transmitted to offspring without changing the genotype, and these aberrant changes in non-coding RNA expression patterns are associated with aging, cancer, neurodegenerative, cardiovascular diseases, etc. Circulating micro RNAs that are sensitive to oxidative stress are reported to be potential biomarkers of cardiovascular diseases, including myocardial infarction, hyper­trophy, ischemia/reperfusion, and heart failure. Many studies are aimed at using microRNAs for therapeutic purposes. The complete expression profile of microRNAs in human atherosclerotic plaques was studied, and the mechanisms affecting their formation were identified. Specific microRNAs and reactive oxygen species were identified as potential biomarkers in human malignancies, which expands the possibilities of their use as therapeutic targets. Unlike micro RNAs, the expression of long RNAs has tissue and species specificity, making them important candidates for specific disease markers. The role of these RNAs in carcinogenesis is being actively studied. A large number of them are disrupted at various types of cancer and may play an im­portant role in the onset, metastasis, and therapeutic response of cancer. Thus, oxidative stress induced by cad­mium affects non-coding RNAs, which disrupts the regulatory mechanisms of the epigenome and affects the deve­lopment of cardiovascular, oncological, pulmonary and other human diseases. The search for the impact of non-coding RNAs on the epigenome is constantly growing and has great scientific and practical prospects in medicine.

Hypermethylation of DNA Methylation Markers in Non-Cirrhotic Hepatocellular Carcinoma.

Aberrant DNA methylation changes have been reported to be associated with carcinogenesis in cirrhotic HCC, but DNA methylation patterns for these non-cirrhotic HCC cases were not examined. Therefore, we sought to investigate DNA methylation changes on non-cirrhotic HCC using reported promising DNA methylation markers (DMMs), including HOXA1, CLEC11A, AK055957, and TSPYL5, on 146 liver tissues using quantitative methylation-specific PCR and methylated DNA sequencing. We observed a high frequency of aberrant methylation changes in the four DMMs through both techniques in non-cirrhotic HCC compared to cirrhosis, hepatitis, and benign lesions (p < 0.05), suggesting that hypermethylation of these DMMs is specific to non-cirrhotic HCC development. Also, the combination of the four DMMs exhibited 78% sensitivity at 80% specificity with an AUC of 0.85 in discriminating non-cirrhotic HCC from hepatitis and benign lesions. In addition, HOXA1 showed a higher aberrant methylation percentage in non-cirrhotic HCC compared to cirrhotic HCC (43.3% versus 13.3%, p = 0.039), which was confirmed using multivariate linear regression (p < 0.05). In summary, we identified aberrant hypermethylation changes in HOXA1, CLEC11A, AK055957, and TSPYL5 in non-cirrhotic HCC tissues compared to cirrhosis, hepatitis, and benign lesions, providing information that could be used as potentially detectable biomarkers for these unusual HCC cases in clinical practice.

Succinate metabolism: a promising therapeutic target for inflammation, ischemia/reperfusion injury and cancer.

Succinate serves as an essential circulating metabolite within the tricarboxylic acid (TCA) cycle and functions as a substrate for succinate dehydrogenase (SDH), thereby contributing to energy production in fundamental mitochondrial metabolic pathways. Aberrant changes in succinate concentrations have been associated with pathological states, including chronic inflammation, ischemia/reperfusion (IR) injury, and cancer, resulting from the exaggerated response of specific immune cells, thereby rendering it a central area of investigation. Recent studies have elucidated the pivotal involvement of succinate and SDH in immunity beyond metabolic processes, particularly in the context of cancer. Current scientific endeavors are concentrated on comprehending the functional repercussions of metabolic modifications, specifically pertaining to succinate and SDH, in immune cells operating within a hypoxic milieu. The efficacy of targeting succinate and SDH alterations to manipulate immune cell functions in hypoxia-related diseases have been demonstrated. Consequently, a comprehensive understanding of succinate's role in metabolism and the regulation of SDH is crucial for effectively targeting succinate and SDH as therapeutic interventions to influence the progression of specific diseases. This review provides a succinct overview of the latest advancements in comprehending the emerging functions of succinate and SDH in metabolic processes. Furthermore, it explores the involvement of succinate, an intermediary of the TCA cycle, in chronic inflammation, IR injury, and cancer, with particular emphasis on the mechanisms underlying succinate accumulation. This review critically assesses the potential of modulating succinate accumulation and metabolism within the hypoxic milieu as a means to combat various diseases. It explores potential targets for therapeutic interventions by focusing on succinate metabolism and the regulation of SDH in hypoxia-related disorders.

Molecular insight into CREBBP and TANGO2 variants causing intellectual disability.

Intellectual disability (ID) can be associated with different syndromes such as Rubinstein-Taybi syndrome (RSTS) and can also be related to conditions such as metabolic encephalomyopathic crises, recurrent,with rhabdomyolysis, cardiac arrhythmias and neurodegeneration. Rare congenital RSTS1 (OMIM 180849) is characterized by mental and growth retardation, significant and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms, and an elevated risk of malignancies. Microdeletions and point mutations in the CREB-binding protein (CREBBP) gene, located at 16p13.3, have been reported to cause RSTS. By contrast, TANGO2-related metabolic encephalopathy and arrhythmia (TRMEA) is a rare metabolic condition that causes repeated metabolic crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias and encephalopathy with cognitive decline. Clinicians need more clinical and genetic evidence to detect and comprehend the phenotypic spectrum of this disorder. Exome sequencing was used to identify the disease-causing variants in two affected families A and B from District Kohat and District Karak, Khyber Pakhtunkhwa. Affected individuals from both families presented symptoms of ID, developmental delay and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing. In the present study, two families (A and B) exhibiting various forms of IDs were enrolled. In Family A, exome sequencing revealed a novel missense variant (NM 004380.3: c.4571A>G; NP_004371.2: p.Lys1524Arg) in the CREBBP gene, whereas, in Family B, a splice site variant (NM 152906.7: c.605 + 1G>A) in the TANGO2 gene was identified. Sanger sequencing of both variants confirmed their segregation with ID in both families. The in silico tools verified the aberrant changes in the CREBBP protein structure. Wild-type and mutant CREBBP protein structures were superimposed and conformational changes were observed likely altering the protein function. RSTS and TRMEA are exceedingly rare disorders for which specific clinical characteristics have been clearly established, but more investigations are underway and required. Multicenter studies are needed to increase our understanding of the clinical phenotypes, mainly showing the genotype-phenotype associations.

Imprinted Long Non-Coding RNAs in Mammalian Development and Disease.

Imprinted genes play diverse roles in mammalian development, homeostasis, and disease. Most imprinted chromosomal domains express one or more long non-coding RNAs (lncRNAs). Several of these lncRNAs are strictly nuclear and their mono-allelic expression controls in cis the expression of protein-coding genes, often developmentally regulated. Some imprinted lncRNAs act in trans as well, controlling target gene expression elsewhere in the genome. The regulation of imprinted gene expression-including that of imprinted lncRNAs-is susceptible to stochastic and environmentally triggered epigenetic changes in the early embryo. These aberrant changes persist during subsequent development and have long-term phenotypic consequences. This review focuses on the expression and the cis- and trans-regulatory roles of imprinted lncRNAs and describes human disease syndromes associated with their perturbed expression.

Tau Protein Induces Aberrant Alternative Splicing Changes in PS19 Transgenic Mice

To explore through big data analysis whether aberrant alternative splicing (AS) events precede tau P301S-induced neurodegenerative phenotype in 6-month-old PS19 mice. The original sequencing files of the GSE182170 dataset was downloaded from the European Nucleotide Archive (ENA) database with axel, aligned to the reference genome of the ENSEMBL database by using STAR software, and common AS event analysis and visualization were performed with rMATS and rmats2sashimiplot R packages. RSEM software was utilized for gene transcript quantification, Deseq2, edgeR, and limma R packages were used for differential expression analysis, and clusterProfiler R package was applied for GO enrichment analysis. String and Cytoscape were used for protein-protein interaction (PPI) analysis. Gene expression correlation analysis was performed with ggcorrplot R package. AS events were validated using PCR followed by agarose electrophoresis. A total of 8 079 AS events were identified with rMATS and 117 significant AS events (ΔPSI>0.1, sequencing coverage >1) were selected eventually. The most frequent type of AS event was skipped exon (SE) (50.43%), followed by alternative 3' splice site (A3SS) and mutually exclusive exons (MXE). GO enrichment analysis revealed that synapse organization genes were aberrantly spliced in SE events and spliceosome genes were spliced in A3SS events. PPI and correlation analyses showed that the splicing factor Snrpn was significantly associated with the largest number of transcripts. Agarose electrophoresis confirmed the aberrant AS event of the Lrp8 gene in PS19 mice. Dysregulated splicing factors may contribute to tau P301S-induced aberrant AS changes. The study also increases the understanding of the cycling of tau protein and splicing factors in tauopathies.

Surgical Technique to Treat Presbyopic Inlay-Associated Corneal Haze With Sequential Excimer Photoablation: A Case Series.

To describe an approach using sequential excimer laser ablation of the stromal surface of the corneal flap with or without subsequent excimer ablation to the stromal bed to reduce presbyopic inlay-associated corneal haze. Twelve patients who underwent KAMRA inlay (Acufocus) explantation due to corneal haze were included. The mean interval between explantation and the primary surgery (phototherapeutic keratotomy [PTK] to corneal flap) was 16.2 ± 29.7 months (range = 1 to 83 months). The corneal flap was lifted and laid on an evisceration spoon and an excimer laser was used to ablate the flap stroma by 30 to 40 µm depth. Subsequently, an excimer laser was used to ablate and treat the stromal bed following a second flap lift according to the manifest refraction, leaving a minimal residual stromal bed thickness of greater than 300 µm. For both procedures, mitomycin C 0.02% was applied to the stromal bed before the flap was replaced and a bandage contact lens applied. Reductions in corneal haze were observed, following PTK to the corneal flap with or without photorefractive keratectomy (PRK) to the stromal bed, both clinically and on imaging. No significant changes in uncorrected distance visual acuity (P = .442) and corrected distance visual acuity (P = .565) were observed. Improvements were observed for both spherical equivalent refractive errors (P = .036) and corneal light backscatter (P = .019). There were significant improvements in spherical aberrations (P = .014) but no changes in total lower and higher order aberrations. PTK to the corneal flap with or without subsequent stromal bed PRK is an effective technique in treating corneal haze following presbyopic inlay explantation. [J Refract Surg. 2023;39(9):639-646.].

Prophylactic feeding of neomycin to Holstein calves alters gut microbiota, bile acid metabolism, and expression of genes involved in immunometabolic regulation.

The objective of this study was to evaluate the effects of prophylactic neomycin administration on Holstein bull calves' intestinal microbiota, bile acid (BA) metabolism, and transcript abundance of genes related to BA metabolism. A total of 36 calves were blocked by body weight and assigned to either non-medicated milk replacer (CTL), or neomycin for 14 days (ST) or 28 days (LT) in their milk replacer. At the end of the study, calves were euthanized to collect tissue and digesta samples from the gastrointestinal tract, liver, and adipose tissue for analysis of intestinal microbial diversity, bile acid concentration and profile in various body tissues, and gene expression related to bile acid, lipid, carbohydrate metabolism, and inflammation. Calves that received prophylactic administration of neomycin for 28 d (LT) had reduced species richness (chao1 index), and tended to have reduced phylogenetic diversity in the ileum tissue. The relative abundance of Lactobacillus, and Bifidobacterium in ileum and colon digesta were decreased in LT compared with CTL. Concentrations of primary, secondary, and total BA were increased by ST in ileal tissue. In plasma, ST and LT treatments had lower concentrations of secondary BA. Gene expression of the BA receptor FXR was increased in ileum and liver by LT compared to CTL. The expression of FXR and TGR5 in the liver was increased in the ST group compared with CTL, and in adipose tissue, 5 genes related to triglyceride, gluconeogenesis, and immune activation were differentially expressed between CTL and ST. In conclusion, we provide evidence that prophylactic administration of neomycin leads to aberrant changes in BA concentration and profile in different compartments of the enterohepatic system through a process that possibly entails antimicrobial disruption of key bacterial groups, which persists even after cessation of neomycin administration. Additionally, we uncovered an apparent link between dysregulated BA metabolism and changes in lipid metabolism and immune activation in adipose tissue and liver.

Changes in Corneal Epithelial Thickness in Relation to Vision, Contrast Sensitivity and Ocular Aberrations After Lasik

Purpose: The assessment of changes in corneal epithelial thickness at the center of the cornea (ET center) and at the apex of the cornea (ET peak) in relation to vision, corneal aberrations (LOAs and HOAs) and contrast sensitivity (C.S) after LASIK. Material and Methods: Twenty-seven patients (27 eyes) with a mean age of 32 years (range 22-50), 9 males and 18 females were included in the study and underwent LASIK. Mean follow up was 12.18 +/- 1.48 (range from 9 to 18 months). Results: A statistically significant difference was found between preoperative and postoperative measurements of ET center and ET peak as well as Zernike coefficients. No statistically significant difference was found for the variable of CS. Conclusion: Changes in corneal aberrations after refractive surgery can be attributed to epithelial thickness increase which can be seen in patients that have undergone LASIK.

Comparative Analysis of Performance of Water-Based Coatings Prepared by Two Kinds of Anti-Bacterial Microcapsules and Nano-Silver Solution on the Surface of Andoung Wood

A nano-silver solution, urea-formaldehyde resin-coated nano-silver solution microcapsules (AgNPS@UF), and melamine-formaldehyde resin-coated chitosan-modified nano-silver solution microcapsules (CS-AgNPS@MF) were added into the coatings at different contents for comparative tests to explore an anti-bacterial agent with the best anti-bacterial properties in the water-based coatings on Andoung wood (Monopetalanthus spp.). As the content of anti-bacterial agents increased, AgNPS@UF had the best anti-bacterial property towards Staphylococcus aureus and Escherichia coli, with anti-bacterial rates of 79.0% and 82.1%, respectively. The optical and mechanical properties of the coating quickly worsened as the content of anti-bacterial agents increased. The anti-bacterial coatings with AgNPS@UF have the minimum chromatic aberration change of 6.5. The anti-bacterial coating with 5% content of AgNPS@UF decreased the aging rate. This coating had good optical properties, and its liquid-resistant level is 2. When the 5% content of AgNPS@UF was added, after high-temperature accelerated aging and ultraviolet (UV) aging, the anti-bacterial rates of the coating with AgNPS@UF decreased toward Escherichia coli from 82.1% to 62.2% and decreased toward Staphylococcus aureus from 79.3% to 61.1%, respectively. This shows that the coating had a long-lasting anti-bacterial property. The anti-bacterial property of the coating after high-temperature accelerated aging was superior to that after the UV aging. The incorporation of AgNPS@UF in water-based coatings protects people from the risks of Escherichia coli and Staphylococcus aureus more effectively with long-lasting property. The research results provide a reference for the preparation of anti-bacterial water-based coatings on the surface of the Andoung wood.

Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments.

Non-alcoholic fatty liver disease (NAFLD) causes significant global disease burden and is a leading cause of mortality. NAFLD induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of NAFLD is widely recognised, the precise triggers for disease progression are still to be fully elucidated. Furthermore, the propagation to cirrhosis is poorly understood. Whilst some progress in terms of treatment options have been explored, an incomplete understanding of the hepatic cellular and molecular alterations limits their clinical utility. We have therefore reviewed some of the key pathways responsible for the pathogenesis of NAFLD such as innate and adaptative immunity, lipotoxicity and fibrogenesis, and highlighted current trials and treatment options for NAFLD patients.

Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats.

Background: One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes's impairment of spatial learning memory. Methods: High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines. Results: Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aβ accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3β signaling pathway was restored by tirzepatide. Conclusion: Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.

DNA N6-methyladenine methylase N6AMT1 controls neuropathic pain through epigenetically modifying Kcnj16 in dorsal horn neurons.

Nerve injury-induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m 6 A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m 6 A-specific DNA methyltransferase 1 ( N6amt1 ) in dorsal horn neurons. This decrease was attributed, at least partly, to a reduction in transcription factor Nr2f6 . Rescuing the decrease in N6amt1 reversed the loss of m 6 A at the promoter for inwardly rectifying potassium channel subfamily J member 16 ( Kcnj16 ), mitigating the nerve injury-induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m 6 A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain-like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m 6 A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m 6 A modification may be a potential new target for analgesic and treatment strategies.

Azoramide prevents MPP+-induced dopaminergic neuronal death via upregulating ER chaperone BiP expression

Progressive death of dopaminergic (DA) neurons is the main cause of Parkinson's disease (PD). The discovery of drug candidates to prevent DA neuronal death is required to address the pathological aspects and alter the process of PD. Azoramide is a new small molecule compound targeting ER stress, which was originally developed for the treatment of diabetes. In this study, pre-treatment with Azoramide was found to suppress mitochondria-targeting neurotoxin MPP+-induced DA neuronal death and locomotor defects in zebrafish larvae. Further study showed that pre-treatment with Azoramide significantly attenuated MPP+-induced SH-SY5Y cell death by reducing aberrant changes in nuclear morphology, mitochondrial membrane potential, intracellular reactive oxygen species, and apoptotic biomarkers. The mechanistic study revealed that Azoramide was able to up-regulate the expression of ER chaperone BiP and thereby prevented MPP+-induced BiP decrease. Furthermore, pre-treatment with Azoramide failed to suppress MPP+-induced cytotoxicity in the presence of the BiP inhibitor HA15. Taken together, these results suggested that Azoramide is a potential neuroprotectant with pro-survival effects against MPP+-induced cell death through up-regulating BiP expression.

One-year clinical efficacy evaluation of selective corneal wavefront aberration-guided FS-LASIK correction in patients with high myopia.

To evaluate the effectiveness, safety, predictability, precision and changes of higher-order aberrations (HOAs) on corneal front surface of selective corneal wavefront aberration-guided femtosecond laser-assisted in situ keratomileusis (CW-FS-LASIK) in patients with high myopia 1-year postoperatively. Totally 74 eyes of 37 patients with high myopia or myopic astigmatism in both the eyes who underwent the CW-FS-LASIK procedure in Xi'an Gaoxin Hospital from January 2021 to June 2021 were included. The changes of uncorrected distance visual acuity (UDVA), best corrected visual acuity (BCVA), spherical equivalent refraction (SER), astigmatism, HOAs and Strehl ratio (SR) on the anterior surface of the cornea after 1y of the surgery were analyzed. At postoperative 1y, the UDVA (logMAR) of 74 eyes (100%) reached 0 or better, including 0 in 8 eyes (10.81%), -0.1 in 45 eyes (60.81%), and -0.2 in 21 eyes (28.38%). The effectiveness index was 1.29±0.134. There was no decrease in postoperative BCVA compared with preoperative BCVA in all patients. Postoperative BCVA was the same in 44 eyes (59.46%) as preoperative BCVA, increased by 1 line in 23 eyes (31.08%) and increased by 2 lines in 7 eyes (9.46%) compared with preoperative BCVA. The safety index was 1.11±0.159. The estimated corrected SER before surgery was (-7.76±1.21) D, and the actual corrected SER was (-7.83±1.25) D (Y=0.9811X+0.2156, R2=0.9084). There was a high correlation between the estimated corrected SER and the actual corrected SER. The postoperative SER in 74 eyes (100%) was within ±0.75 D. The postoperative astigmatism of all was within -0.75 D to 0. Root mean square (RMS) HOAs of spherical aberration and SR within 5 mm of the corneal front surface were all increased compared with those before operation (P<0.01). The total coma, horizontal coma and vertical coma were all decreased compared with those before operation (P<0.01). There was no statistically significant difference in horizontal trefoil and vertical trefoil compared with preoperative ones (P>0.05). Selective CW-FS-LASIK for correction of high myopia is effective, safe, predictive, and accurate. For patients with preoperative RMS HOAs over 0.25 defocus equivalent, postoperative coma aberration can be significantly reduced, and SR value can be increased, thus corneal imaging quality can be improved.

Balancing lysosome abundance in health and disease.

Lysosomes are catabolic organelles that govern numerous cellular processes, including macromolecule degradation, nutrient signalling and ion homeostasis. Aberrant changes in lysosome abundance are implicated in human diseases. Here we outline the mechanisms of lysosome biogenesis and turnover, and discuss how changes in the lysosome pool impact physiological and pathophysiological processes.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery. TBI caused dynamic white and gray matter alterations with significant differences in DTI values and injury-induced alterations in cerebral blood flow (CBF) as measured by PWI. Regional abnormalities after TBI were observed in T2-weighted images that showed hyperintense cortical lesions and significant cerebral atrophy in these hyperintense areas 1 year after TBI. Temporal DTI values indicated significant injury-induced changes in anisotropy in major white matter tracts, the corpus callosum and external capsule, and in gray matter, the hippocampus and cortex, at both early and chronic time points. These alterations were primarily injury-severity dependent with severe TBI exhibiting a greater degree of change relative to uninjured controls. PWI evaluating CBF revealed sustained global reductions in the cortex and in the hippocampus at most time points in an injury-independent manner. We next sought to investigate prognostic correlations across MRI metrics, timepoints, and cerebral pathology, and found that diffusion abnormalities and reductions in CBF significantly correlated with specific vulnerable structures at multiple time points, as well as with the degree of cerebral atrophy observed 1 year after TBI. This study further supports using DTI and PWI as a means of prognostic imaging for progressive structural changes after TBI and emphasizes the progressive nature of TBI damage.