Identification and Validation of Glomeruli Cellular Senescence-Related Genes in Diabetic Nephropathy by Multiomics.

Accumulating evidence indicates that cellular premature senescence of the glomerulus, including endothelial cells, mesangial cells, and podocytes leads to diabetic nephropathy (DN), and DN is regarded as a clinical model of premature senescence. However, the role of cellular senescence-associated genes in the glomerulus in DN progression remains unclear. Therefore, this work aims to identify and validate potential cellular aging-related genes in the glomerulus in DN to provide novel clues for DN treatment based on anti-aging. The microarray GSE96804 dataset, including 41 diabetic glomeruli and 20 control glomeruli, is retrieved from the Gene Expression Omnibus (GEO) database and cellular senescence-related genes (CSRGs) are obtained from the GeneCards database and literature reports. Subsequently, PPI, GO, and KEGG enrichment are analyzed by screening the intersection between differentially expressed genes (DEGs) and CSRGs. scRNA-seq dataset GSE127235 is used to verify core genes expression in glomerulocytes of mice. Finally, db/db mice are utilized to validate the hub gene expression in the glomeruli, and high glucose-induced mesangial cells are used to confirm key gene expression. This study reveals that FOS and ZFP36 may play an anti-aging role in DN to ameliorate cell intracellular premature aging in mesangial cells of glomeruli.

A Cyclopentanone Compound Attenuates the Over-Accumulation of Extracellular Matrix and Fibrosis in Diabetic Nephropathy via Downregulating the TGF-ß/p38MAPK Axis.

Excessive accumulation of the extracellular matrix (ECM) is a crucial pathological process in chronic kidney diseases, such as diabetic nephropathy, etc. The underlying mechanisms of how to decrease ECM deposition to improve diabetic nephropathy remain elusive. The present study investigated whether cyclopentanone compound H8 alleviated ECM over-deposition and fibrosis to prevent and treat diabetic nephropathy. HK-2 cell viability after treatment with H8 was measured by an MTT assay. ECM alterations and renal fibrosis were identified in vitro and in vivo. A pharmacological antagonist was used to detect associations between H8 and the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. H8 binding was identified through computer simulation methods. Studies conducted on high glucose and transforming growth factor ß1 (TGF-ß1)-stimulated HK-2 cells revealed that the p38MAPK inhibitor SB 202190 and H8 had similar pharmacological effects. In addition, excessive ECM accumulation and fibrosis in diabetic nephropathy were remarkably improved after H8 administration in vivo and in vitro. Finally, the two molecular docking models further proved that H8 is a specific p38MAPK inhibitor that forms a hydrogen bond with the LYS-53 residue of p38MAPK. The cyclopentanone compound H8 alleviated the over-deposition of ECM and the development of fibrosis in diabetic nephropathy by suppressing the TGF-ß/p38MAPK axis.

Curcumin and Its Analogs in Non-Small Cell Lung Cancer Treatment: Challenges and Expectations.

Researchers have made crucial advances in understanding the pathogenesis and therapeutics of non-small cell lung cancer (NSCLC), improving our understanding of lung tumor biology and progression. Although the survival of NSCLC patients has improved due to chemoradiotherapy, targeted therapy, and immunotherapy, overall NSCLC recovery and survival rates remain low. Thus, there is an urgent need for the continued development of novel NSCLC drugs or combination therapies with less toxicity. Although the anticancer effectiveness of curcumin (Cur) and some Cur analogs has been reported in many studies, the results of clinical trials have been inconsistent. Therefore, in this review, we collected the latest related reports about the anti-NSCLC mechanisms of Cur, its analogs, and Cur in combination with other chemotherapeutic agents via the Pubmed database (accessed on 18 June 2022). Furthermore, we speculated on the interplay of Cur and various molecular targets relevant to NSCLC with discovery studio and collected clinical trials of Cur against NSCLC to clarify the role of Cur and its analogs in NSCLC treatment. Despite their challenges, Cur/Cur analogs may serve as promising therapeutic agents or adjuvants for lung carcinoma treatment.

Curcumin and Its Analogs as Potential Epigenetic Modulators: Prevention of Diabetes and Its Complications.

BACKGROUND: The pathobiology of diabetes and associated complications has been widely researched in various countries, but effective prevention and treatment methods are still insufficient. Diabetes is a metabolic disorder of carbohydrates, fats, and proteins caused by an absence of insulin or insulin resistance, which mediates an increase of oxidative stress, release of inflammatory factors, and macro- or micro-circulation dysfunctions, ultimately developing into diverse complications. SUMMARY: In the last decade through pathogenesis research, epigenetics has been found to affect metabolic diseases. Particularly, DNA methylation, histone acetylation, and miRNAs promote or inhibit diabetes and complications by regulating the expression of related factors. Curcumin has a wide range of beneficial pharmacological activities, including anti-inflammatory, anti-oxidation, anticancer, anti-diabetes, anti-rheumatism, and increased immunity. Key Messages: In this review, we discuss the effects of curcumin and analogs on diabetes and associated complications through epigenetics, and we summarize the preclinical and clinical researches for curcumin and its analogs in terms of management of diabetes and associated complications, which may provide an insight into the development of targeted therapy of endocrine diseases.

Curcumin in age-related diseases.

The world's aging population continues to grow at an unprecedented rate. Consequently, age-related diseases including diabetes and diabetic complication, neurodegenerative disease, cardiovascular disease have become a health problem that cannot be ignored. The purpose of this review is to summarize the benefits of curcumin for age-related diseases, and present the molecular mechanisms for this effect. Curcumin-a natural plant extract, has received worldwide attention in recent years, due to its low toxicity, low cost and significant effects. It is derived from the spice turmeric and has been used in traditional medicine to improve diabetes. Many reports indicate that curcumin can regulate blood sugar levels, decrease blood pressure, protect nerve cells, and enhance immunity. In addition, there is evidence for its antioxidant, anti-infective, anti-inflammatory, as well as promoting wound recovery, which suggests that curcumin may be especially beneficial for the elderly.

11ß-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Development by Lentiviral Screening Based on Computational Modeling.

In this study, rat and human 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) have been cloned by lentiviral transduction and expressed by CHO-K1 cells. The results showed that recombinant plasmids contained R11bhsd1 or H11bhsd1 have been constructed, which is consistent with the gene bank respectively. A clone cell was selected with G418 and cultivated to express 11ß-HSD1. 11ß-HSD1 catalytic activity of rat and human were 99.5 and 98.7%, respectively, determined by scanning radiometer. And the cloned CHO-K1 cells expressed the protein of 11ß-HSD1 in a long-term and stable manner, which makes it suitable for screening 11ß-HSD1 inhibitor. The three-dimensional structure of 11ß-HSD1 was used for studying the interaction between inhibitor and enzyme by the binding poses predicted by AutoDock and LeDock software. The docking results revealed that compound 8 forms 2 hydrogen bonds with the residues of Gly-216 and Ile-218 in 11ß-HSD1, that is to say compound 8 maybe a good 11ß-HSD1 inhibitor. Moreover, C57BL/6 mice with R11bHsd1 overexpression had a higher body weight, glucose, total cholesterol, and triglyceride levels compared to the mice treated with an empty viral vector. The results might provide a beneficial foundation for selecting inhibitors of 11ß-HSD1 or for researching drug candidate mechanisms.

High-responsivity UV-Vis Photodetector Based on Transferable WS2 Film Deposited by Magnetron Sputtering.

The two-dimensional layered semiconducting tungsten disulfide (WS2) film exhibits great promising prospects in the photoelectrical applications because of its unique photoelectrical conversion property. Herein, in this paper, we report the simple and scalable fabrication of homogeneous, large-size and transferable WS2 films with tens-of-nanometers thickness through magnetron sputtering and post annealing process. The produced WS2 films with low resistance (4.2 kΩ) are used to fabricate broadband sensitive photodetectors in the ultraviolet to visible region. The photodetectors exhibit excellent photoresponse properties, with a high responsivity of 53.3 A/W and a high detectivity of 1.22 × 10(11) Jones at 365 nm. The strategy reported paves new way towards the large scale growth of transferable high quality, uniform WS2 films for various important applications including high performance photodetectors, solar cell, photoelectrochemical cell and so on.

Infrared light gated MoS2 field effect transistor.

Molybdenum disulfide (MoS2) as a promising 2D material has attracted extensive attentions due to its unique physical, optical and electrical properties. In this work, we demonstrate an infrared (IR) light gated MoS2 transistor through a device composed of MoS2 monolayer and a ferroelectric single crystal Pb(Mg(1/3)Nb(2/3))O3-PbTiO3 (PMN-PT). With a monolayer MoS2 onto the top surface of (111) PMN-PT crystal, the drain current of MoS2 channel can be modulated with infrared illumination and this modulation process is reversible. Thus, the transistor can work as a new kind of IR photodetector with a high IR responsivity of 114%/Wcm⁻². The IR response of MoS2 transistor is attributed to the polarization change of PMN-PT single crystal induced by the pyroelectric effect which results in a field effect. Our result promises the application of MoS2 2D material in infrared optoelectronic devices. Combining with the intrinsic photocurrent feature of MoS2 in the visible range, the MoS2 on ferroelectric single crystal may be sensitive to a broadband wavelength of light.

Bilayer graphene based surface passivation enhanced nano structured self-powered near-infrared photodetector.

A simple methyl-terminated (-CH(3)) surface passivation approach has been employed to enhance the performance of the bilayer graphene/Si nanohole array (BLG/SiNH array) Schottky junction based self-powered near infrared photodetector (SPNIRPD). The as-fabricated SPNIRPD exhibits high sensitivity to light at near infrared region at zero bias voltage. The I(light)/I(dark) ratio measured is 1.43 × 10(7), which is more than an order of magnitude improvement compared with the sample without passivation (~6.4 × 10(5)). Its corresponding responsivity and detectivity are 0.328 AW(-1) and 6.03 × 10(13) cmHz(1/2)W(-1), respectively. The demonstrated results have confirmed the high-performance SPNIRPD compared with the photo-detectors of similar type and its great potential application in future optoelectronic devices.

Improved multiphoton ultraviolet upconversion photoluminescence in ultrasmall core-shell nanocrystals.

Near-infrared to ultraviolet multiphoton upconversion photoluminescence in ultrasmall Tm3+/Yb3+-codoped CaF2 nanocrystals (∼6.7 nm in size) was observed and further significantly enhanced by growing an active shell of NaYF4:Yb3+. Owing to the active shell, the lanthanide emitters inside the core are effectively prevented from the surface quenchers, and the excitation energy is absorbed more efficiently via the additional luminescence sensitizer Yb3+ embedded in the shell. The details of underlying physics were investigated and discussed. The results present a good ultrasmall luminescent material system for achieving efficient multiphoton upconversion, which shows great potential in versatile industrial and biological applications.