Recognition of differently expressed genes and DNA methylation markers in patients with Lupus nephritis.

Background and Objectives: Systemic lupus erythematosus (SLE) is distinguished by dysregulated immune system activity, resulting in a spectrum of clinical manifestations, with lupus nephritis being particularly prominent. This study endeavors to discern novel targets as potential therapeutic markers for this condition. Methods: Weighted correlation network analysis (WGCNA) was used to construct the network and select the key hub genes in the co-expression module based on the gene expression dataset GSE81622. Subsequently, functional enrichment and pathway analysis were performed for SLE and lupus nephritis. In addition, also identify genes and differences in SLE with lupus nephritis and methylation site. Finally, qRT-PCR and western blot were used to verify the up-regulated expression levels of the selected key genes. Results: Within the co-expression modules constructed by WGCNA, the MElightcyan module exhibited the strongest positive correlation with lupus nephritis (0.4, P = 0.003), while showing a weaker correlation with the control group SLE (0.058) and a negative correlation with the control group (-0.41, P = 0.002). Additionally, the MEgreenyellow module displayed the highest positive correlation with SLE (0.25), but its P value was 0.06, which did not reach statistical significance(P > 0.05). Furthermore, it had a negative correlation with the control group was (-0.38, P = 0.004). The module associated with lupus nephritis was characterized by processes such as neutrophil activation (neutrophil_activation), neutrophil degranulation (neutrophil_degranulation), neutrophil activation involved in immune response (neutrophil_activation_involved_in_immune_response), neutrophils mediated immune (neutrophil_mediated_immunity) and white blood cells degranulation (leukocyte_degranulation) and so on the adjustment of the process. Secondly, in the analysis of SLE samples, the identification of differentially expressed genes revealed 125 genes, with 49 being up-regulated and 76 down-regulated. In the case of lupus nephritis samples, 156 differentially expressed genes were discerned, include in 70 up-regulated and 86 down-regulated genes. When examining differential methylation sites, we observed 12432 such sites in the SLE sample analysis, encompassing 2260 hypermethylation sites and 10172 hypomethylation sites. In the lupus nephritis samples analysis, 9613 differential methylation sites were identified, comprising 4542 hypermethylation sites and 5071 hypomethylation sites. Substantiating our findings, experimental validation of the up-regulated genes in lupus nephritis confirmed increased levels of gene expression and protein expression for CEACAM1 and SLC2A5. Conclusions: We have identified several genes, notably CEACAM1 and SLC2A5, as potential markers for lupus nephritis. Their elevated expression levels and reduced DNA methylation in lupus nephritis contribute to a more comprehensive understanding of the aberrant epigenetic regulation of expression in this condition. These findings hold significant implications for the diagnosis and therapeutic strategies of lupus nephritis.

FOXF2 suppressed esophageal squamous cell carcinoma by reducing M2 TAMs via modulating RNF144A-FTO axis.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers because of its high invasiveness and low survival. Tumor-associated macrophages (TAMs) are closely associated with the tumor cell proliferation, metastasis and immunosuppression. As a member of the FOX family, forkhead box F2 (FOXF2) was down-regulated in ESCC. However, its role in ESCC and TAMs, as well as the underlying mechanism, remains unclear. We found that differentially expressed genes (DEGs) in ESCC were enriched in proliferation, migration, macrophage and cancer pathways. Among these DEGs, FOXF2 caught our eyes. FOXF2 was down-regulated in ESCC. Overexpression FOXF2 inhibited the proliferation of ESCC cells and the M2 polarization of TAMs, but silenced FOXF2 reversed these results. Notably, FOXF2 promoted the transcription of ring finger protein 144A (RNF144A), which is an E3 ubiquitin ligase, causing the ubiquitination and degradation of FTO Alpha-Ketoglutarate Dependent Dioxygenase (FTO), an N6-methyladenosine (m6A) demethylase. Furthermore, overexpression of FTO abolished the effects of FOXF2 on TAM polarization. In conclusion, FOXF2 alleviates ESCC via promoting the transcription of RNF144A which results in the ubiquitylation and degradation of FTO. Targeting FOXF2/RNF144A/FOT axis might be a possible strategy for the treatment of ESCC.

Safety and efficacy of subthreshold micropulse yellow laser for persistent subretinal fluid after scleral bucking a randomized clinical trial.

Persistent subretinal fluid (PSF) after scleral bucking of rhegmatogenous retinal detachment may delay recovery and affect the final visual quality, but with no effective treatment. This study firstly investigated the safety and efficacy of 577 nm yellow subthreshold micropulse laser (SML) on PSF after scleral bucking surgery. This double-masked randomized clinical trial was conducted from December 2020 to October 2022 at Chongqing Aier Eye Hospital. Participants with PSF last for 1 month after scleral bucking surgery with break closed and retina reattachment were recruitment. These participants were treated by 577 nm yellow SML or sham treatment. Funduscopy, optical coherence tomography (OCT) volume change, best corrected vision acuity (BCVA) and visual field test were evaluated for six mouths follow-up. A total of 24 participants were randomized into SML group or Sham group equally. Compared with Sham group, the OCT volume within 6 mm of macular fovea was significantly less in SML group 6 months after therapy (P = 0.048). There were no statistically significant differences of OCT volume at 1, 2 and 3 months from baseline between groups. BCVA of ETDRS letters had no statistically significant difference. Pattern Standard Deviation amelioration (P = 0.039) had statistically significance in SML group compared with Sham group. There were no complications in the 2 groups. These preliminary findings suggest that 577 nm yellow SML therapy could accelerate PSF absorption after scleral bucking surgery.Trial registration: Chinese Clinical Trial Registry No. ChiCTR2000037838, 02/09/2020, https://www.chictr.org.cn/showproj.html?proj=51885 .

Transparent Cap-Assisted Blunt Endoscopic Dissection of Gastric Submucosal Tumours Smaller than 2cm.

OBJECTIVE: To evaluate the safety and effectiveness of transparent cap-assisted blunt dissection (TCABD) in the endoscopic resection of gastric submucosal tumours (G-SMT) smaller than 2cm, as compared with conventional electronic knife dissection. STUDY DESIGN: Randomised controlled analysis. Place and Duration of the Study: Department of Gastrointestinal Surgery, The School of Clinical Medicine, Fujian Medical University, The First Hospital of Putian City, Putian, China, from July 2020 to 2022. METHODOLOGY: Fifty-eight patients having G-SMT smaller than 2cm were included. They were randomly divided into two groups; undergoing transparent cap-assisted blunt dissection (BD group) and conventional endoscopic submucosal excavation (ESE group). The pathology, lesion size in long diameter (mm), operation time, the number of clips used to close the wounds, the number of snare used to resect the tumour, hospital days, hospitalisation expense, en bloc resection rate, and the complications including perforation, postoperative bleeding, and postoperative infection were compared between the two groups. RESULTS: The mean long diameter in the BD group was 9.6 ± 3.6mm, while the conventional ESE group was 10.7 ± 4.5mm. As compared with the conventional ESE group, the operation time, the number of clips used to close the wounds, the number of snare used to resect the tumours, the hospital days, and the hospitalisation expense were all significantly decreased (p <0.05). The perforation rate was lower in the BD group (p <0.05). CONCLUSION: TCABD was effective and safe in the endoscopic resection of G-SMT smaller than 2cm. TCABD could help to reduce the perforation rate, shorten the operation time and hospital days, and decrease the hospitalisation expense in the endoscopic resection of G-SMT. KEY WORDS: Endoscopic submucosal excavation, Endoscopic full-thickness resection, Endoscopic resection, Submucosal tumour, Transparent cap-assisted blunt dissection.

Novel chiral matrine derivatives as potential antitumor agents: Design, synthesis and biological evaluation.

Since the thalidomide incident, research on chiral drugs has escalated immensely. Differences in drug configuration can lead to significant variations in therapeutic efficacy. Matrine, a natural product esteemed for its low toxicity and high water solubility, has garnered significant attention in research endeavors. Nonetheless, its precise target has proven elusive. In this study, we designed and synthesized a novel chiral matrine derivative. Their cytotoxicity against three types of tumor cells was assessed. Comparing the newly synthesized derivatives to the parent matrine, most compounds exhibited significantly enhanced inhibitory effects on cancer cells. Among them, Q12 exhibited the highest activity, with IC50 values of 8.31 µM against rat glioma cells C6, 6.3 µM against human liver cancer cells HepG2 and 7.14 µM against human gastric cancer cells HGC-27, meanwhile showing low toxicity. Based on IC50 values, we constructed a preliminary structure-activity relationship (SAR). Compound Q12 significantly suppressed the cloning and migration of HepG2 cells. Further mechanistic studies indicated that Q12 inhibited Topo I in HepG2 cells, leading to DNA damage, induction of G0/G1 cell cycle arrest and ultimately causing apoptosis. The molecular docking experiments provided a rational binding mode of Q12 with the Topo I-DNA complex. In vivo, experiments demonstrated that Q12 exhibited a higher tumor growth inhibition rate (TGI) compared to the positive control drug Lenvatinib, while maintaining good safety. In summary, it suggests that Topo I might be a potential target for matrine and Q12 represents a promising candidate for cancer treatment.

Design, synthesis and biological evaluation of matrine contains benzimidazole derivatives as dual TOPOI and PARP inhibitors for cancer therapy.

TOPOI inhibitors have long been a focal point in the research and development of antitumor drugs. PARP-1 plays a crucial role in repairing DNA damage induced by TOPOI inhibitors. Thus, concurrent inhibition of TOPOI and PARP-1 has the potential to augment drug activity. Matrine, characterized by low toxicity and good water solubility, offers advantageous properties. In this investigation, a series of benzimidazole matrine derivatives were designed and synthesized using matrine as the lead compound with the aim of developing dual inhibitors targeting both TOPOI and PARP-1. Among these derivatives, Compound B6 exhibited potent inhibitory effects on PARP-1 and TOPOI, effectively suppressing cancer cell proliferation and migration. Mechanistic assessments revealed that B6 induced DNA damage in HGC-27 cells, leading to G0/G1 cell cycle arrest and significant apoptosis. Molecular docking experiments demonstrated that B6 can effectively enter the active pocket of target proteins, where it forms stable hydrogen bonds with amino acid residues. In vivo, experiments demonstrated that B6 exhibited antitumor activity comparable to that of the positive control drug. The tumor growth inhibition rates (TGIs) for irinotecan, B6 and matrine were 87.0%, 75.4% and 9.7%, respectively. Importantly, B6 demonstrated lower toxicity than the positive control drug. Our findings suggest that TOPOI and PARP-1 may represent potential targets for matrine and B6 emerges as a promising candidate for cancer therapy.

The intervention of cannabinoid receptor in chronic and acute kidney disease animal models: a systematic review and meta-analysis.

AIM: Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease. METHODS: PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE's RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury. RESULTS: The blockade or knockout of CB1 could significantly reduce blood urea nitrogen [SMD,- 1.67 (95% CI - 2.27 to - 1.07)], serum creatinine [SMD, - 1.88 (95% CI - 2.91 to - 0.85)], and albuminuria [SMD, - 1.60 (95% CI - 2.16 to - 1.04)] in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine [SMD, - 0.97 (95% CI - 1.83 to - 0.11)] and albuminuria [SMD, - 2.43 (95% CI - 4.63 to - 0.23)] in renal dysfunction animals compared with the control group. CONCLUSIONS: The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.

Early vascular changes after silicone oil removal using optical coherence tomography angiography.

BACKGROUND: This study evaluated the vascular changes in the macular and peripapillary regions before and after silicone oil (SO) removal in patients with rhegmatogenous retinal detachment. METHODS: This single-center case series assessed patients who underwent SO removal at one hospital. Patients who underwent pars plana vitrectomy and perfluoropropane gas tamponade (PPV + C3F8) were selected as controls. Superficial vessel density (SVD) and superficial perfusion density (SPD) in the macular and peripapillary regions were assessed by optical coherence tomography angiography (OCTA). Best-corrected visual acuity (BCVA) was assessed using LogMAR. RESULTS: Fifty eyes were administered SO tamponade, 54 SO tamponade(SOT) contralateral eyes, 29 PPV + C3F8 eyes, and 27 PPV + C3F8 contralateral eyes were selected. SVD and SPD in the macular region were lower in eyes administered SO tamponade compared with SOT contralateral eyes (P < 0.01). Except for the central area, SVD and SPD in the other areas of the peripapillary region were reduced after SO tamponade without SO removal (P < 0.01). No significant differences were found in SVD and SPD between PPV + C3F8 contralateral and PPV + C3F8 eyes. After SO removal, macular SVD and SPD showed significant improvements compared with preoperative values, but no improvements in SVD and SPD were observed in the peripapillary region. BCVA (LogMAR) decreased post-operation and was negatively correlated with macular SVD and SPD. CONCLUSIONS: SVD and SPD are decreased during SO tamponade and increased in the macular region of eyes that underwent SO removal, suggesting a possible mechanism for reduced visual acuity during or after SO tamponade. TRIAL REGISTRATION: Registration date: 22/05/2019; Registration number, ChiCTR1900023322; Registration site, Chinese Clinical Trial Registry (ChiCTR).

Different lens power calculation formulas for the prediction of refractive outcome after phacoemulsification with silicone oil removal.

BACKGROUND: Formulas predicting intraocular lens power have not been compared in silicone oil-tamponaded eyes. The study aims to compare six intraocular lens power assessment formulas in silicone oil-tamponaded eyes. METHODS: This prospective study included patients with silicone oil-tamponaded eyes scheduled for silicone oil removal, phacoemulsification, and intraocular lens implantation at Chongqing Aier Eye Hospital (June 2019 to December 2019). Implanted intraocular lens power was used to predict postsurgical spherical equivalence using SRK/T, Holladay 1, Holladay 2, Haigis, Hoffer Q, and Barrett Universal II, and assess those formula's predictive accuracy with predictive error. RESULTS: The analysis included 47 eyes in 47 patients (28 and 19 eyes with normal and long axial length, respectively). Postoperative spherical equivalence at 6 months in normal and long axial length eyes was - 0.6 ± 0.96 and - 0.8 ± 1.52 D, respectively. Predictive error values for SRK/T, Holladay 1, Holladay 2, Haigis, and Hoffer Q and Barrett Universal II were - 0.18 ± 0.92, - 0.15 ± 0.88, - 0.06 ± 0.94, - 0.15 ± 0.87, and - 0.05 ± 0.90 D and - 0.06 ± 0.90, respectively, for normal axial length eyes and 0.15 ± 1.16, 0.46 ± 1.17, 0.28 ± 1.11, - 0.04 ± 1.12, 0.49 ± 1.09 D and 0.11 ± 0.99, respectively, for long axial length eyes. For normal axial length eyes, predicted outcomes were similar to actual outcomes for all formulas. For long axial length eyes, predicted outcomes differed significantly from measured postsurgical values for Holladay 1, Holladay 2, and Hoffer Q (P < 0.05) but not SRK/T or Haigis or Barrett Universal II . CONCLUSIONS: The formulas had comparable predictive accuracy in silicone oil-tamponaded eyes with normal axial length, but Haigis or SRK/T or Barrett Universal II may be preferable in long axial length eyes. TRIAL REGISTRATION: ChiCTR1900023215.

Metabolic Understanding of the Genetic Dysregulation in the Tumor Microenvironment of Kidney Renal Clear Cell Carcinoma.

The metabolic dysregulation is a hallmark of cancers including KIRC, specifically caused by alterations in metabolic genes. Currently, a lack of consensus exists between metabolic signatures in the tumor microenvironment. Here, in this study, we observed the significant correlations of differentially expressed metabolic genes (DEmGs) between KIRC and the related normal samples. Briefly, we collected sets of metabolic genes through RNA-seq data of KIRC and normal tissues from TCGA, followed by the identification of KIRC-related DEmGs. Next, patients were classified into three clusters, and using WGCNA, we identified metabolic genes involved in the survival among different clusters. Furthermore, we investigated survival and clinical parameters along with immune infiltration in the clusters. At the same time, we constructed and validated a prediction model based on these DEmGs. These analyses revealed that the patients having high expression of DEmGs showed poor survival, while infiltration of less-immune cells was associated with the metastasis of KIRC. In the end, we identified NUDT1 as a hub gene as it showed significantly high expression in KIRC samples as well as associated with the survival and prognosis of the patients. Further analysis revealed the oncogenic role of NUDT1 in 786-O and ACHN cells. Thus, we conclude that NUDT1 could be a potential diagnostic and prognostic marker for KIRC.

HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis.

Diabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.

Non-stationary component extraction in noisy multicomponent signal using polynomial chirping Fourier transform.

Inspired by track-before-detection technology in radar, a novel time-frequency transform, namely polynomial chirping Fourier transform (PCFT), is exploited to extract components from noisy multicomponent signal. The PCFT combines advantages of Fourier transform and polynomial chirplet transform to accumulate component energy along a polynomial chirping curve in the time-frequency plane. The particle swarm optimization algorithm is employed to search optimal polynomial parameters with which the PCFT will achieve a most concentrated energy ridge in the time-frequency plane for the target component. The component can be well separated in the polynomial chirping Fourier domain with a narrow-band filter and then reconstructed by inverse PCFT. Furthermore, an iterative procedure, involving parameter estimation, PCFT, filtering and recovery, is introduced to extract components from a noisy multicomponent signal successively. The Simulations and experiments show that the proposed method has better performance in component extraction from noisy multicomponent signal as well as provides more time-frequency details about the analyzed signal than conventional methods.

Characterization and photocatalytic properties of Ni-doped Sr(10)Bi(6)O(24-y).

The compound Sr(10)Bi(6)O(24-y) doped with Ni was prepared by solid-state reaction method. The obtained powders were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), UV-vis diffuse reflectance spectra and X-ray photoemission spectra (XPS). The Ni-doped Sr(10)Bi(6)O(24-y) samples assume a cubic perovskite structure with space group Fm3m (225). Bi in Sr(10)Bi(6)O(24-y) exists in the valence state of Bi(II). Photocatalytic activities of the prepared samples were evaluated using acid red G as a model organic compound. The results show that doping with 0.5 wt.% Ni can significantly improve the photoactivity of the compound Sr(10)Bi(6)O(24-y).