Inhibition of Pyroptosis of Renal Tubular Epithelial Cells by Puerarin via Regulation of lncRNA NEAT1 Ameliorating Chronic Renal Failure.

INTRODUCTION: Chronic kidney disease (CKD) is one of the major chronic human diseases worldwide. Puerarin, extensively used in traditional Chinese medicine, has shown favorable clinical effects in treating CKD. Here, we aimed to elucidate the mechanism by which puerarin alleviates CKD. METHODS: We constructed an animal model of CKD and intragastrically administered 400 mg/kg puerarin to the rat models. The extent of kidney injury was evaluated by performing hematoxylin and eosin staining. Then, we quantified the renal function indicators, inflammatory cytokines, apoptosis-related factors, and pyroptosis-related factors. HK-2 cells were treated with lipopolysaccharide (400 ng/mL) in H2O2 (200 µM) to induce oxidative stress. Then, the cells were treated with puerarin and transfected with overexpressed lncRNA NEAT1 vectors. Finally, the regulatory functions of lncRNA NEAT1 in cell apoptosis and pyroptosis were investigated. RESULTS: Puerarin treatment alleviated kidney damage and suppressed inflammation and apoptosis in the CKD rat model. Puerarin ameliorated pyroptosis in the CKD model by inhibiting caspase-1 and GSDMD-N expression. LncRNA NEAT1 was down-regulated in the CKD model after puerarin treatment. Puerarin enhanced cell viability when lncRNA NEAT1 was overexpressed, and the inhibition of apoptosis was reversed in the LPS/H2O2-stimulated HK-2 cells. Furthermore, lncRNA NEAT1 overexpression blocked the anti-pyroptosis effect of Puerarin in the CKD model. CONCLUSION: Puerarin inhibits pyroptosis and inflammation by regulating lncRNA NEAT1, thereby ameliorating CKD.  DOI: 10.52547/ijkd.7565.

Puerarin alleviates chronic renal failure-induced pyroptosis in renal tubular epithelial cells by targeting miR-342-3p/TGF-ß/SMAD axis.

BACKGROUND: Chronic renal failure (CRF) is the result of kidney damage. Puerarin is a flavonoid with specific nephroprotective effect, but its effect on CRF needs further research. This study explored the effect of puerarin on CRF and the potential molecular mechanism. METHODS: Adenine was used to establish an in vivo CRF model in rats, and rats were intragastrically administered with puerarin at a dose of 400 mg/kg body weight once a day from day 1 to day 28. Hematoxylin and eosin (HE) and Masson staining were used to observe the morphology and fibrosis of kidney tissue. Lipopolysaccharide (LPS) (400 ng/mL)/H2O2 (200 µM) was applied to human kidney 2 (HK-2) cells to construct an in vitro CRF model. Enzyme-linked immunosorbent assay (ELISA) was performed to validate interleukin (IL)-1ß and IL-18 levels. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to detect microRNA (miR)-342-3p levels. Transforming growth factor beta (TGF-ß)1, SMAD2, SMAD3, and pyroptosis marker proteins were detected by Western blot. The interaction between miR-342-3p and TGF-ß/SMAD was determined by a dual-luciferase reporter gene assay. Cell Counting Kit-8 (CCK-8) assay was utilized to determine cell viability. RESULTS: In the CRF model, puerarin alleviated renal injury and fibrosis and reduced creatinine (Cr) and blood urea nitrogen (BUN) levels. At the same time, miR-342-3p was downregulated, while the TGF-ß/SMAD axis was activated and levels of IL-1ß and IL-18 were increased. After treatment of CRF rats with puerarin, the expression level of miR-342-3p was increased, the TGF-ß/SMAD axis was inhibited, and the secretion of IL-1ß and IL-18 was decreased. MiR-342-3p directly bound to and negatively regulated the expression of TGF-ß1, SMAD2, and SMAD3. In the in vitro CRF model, miR-342-3p inhibited HK-2 cell pyroptosis by inhibiting the TGF-ß/SMAD axis. CONCLUSION: Puerarin reduced renal injury and pyroptosis in CRF rats by targeting the miR-342-3p/TGF-ß/SMAD axis.

ALDOB plays a tumor-suppressive role by inhibiting AKT activation in gastric cancer.

Enhanced aerobic glycolysis has been one of the cancer hallmarks. Cancerous cells develop certain alterations during glucose metabolism for supporting their infinite growth requirement and metastasis. Therefore, targeting metabolism, for instance, crucial glycolytic enzymes, will provide a novel therapeutic strategy to treat cancer. Aldolase B (ALDOB), as a glycolytic enzyme, plays a contentious role in cancers and can either act against the tumor or as an oncogenic enzyme. The precise role of ALDOB in gastric cancer (GC) and the endogenous process is elusive and needs further exploration. This investigation revealed that ALDOB expression was markedly decreased in GC tissues. Furthermore, ALDOB inhibition was notably linked with tumor size, depth of tumor invasion, lymph node metastasis (LNM), tumor node metastases (TNM) staging, and substandard prognosis of GC. The assessment of loss- and gain-of-function indicated that ALDOB inhibited the growth and the migrative ability of GC cells, suggesting its anti-tumor role. Mechanistic studies revealed that ALDOB modulates the AKT signaling pathway. The increase in growth and cells' ability to migrate stimulated by ALDOB inhibition was partially impaired in cells under the influence of AKT inhibitors. The overall data highlights a novel target, the ALDOB/AKT signaling axis for the treatment of GC.

Gold Triangular Nanoprisms: Anisotropic Plasmonic Materials with Unique Structures and Properties.

As a novel type of anisotropic inorganic nanomaterials, gold triangular nanoprisms (AuTNPs) have been widely studied for their well-defined structures and excellent plasmonic properties. This review starts with synthetic methodology, combing through the early thermal solution method to the mature seed-mediated method and seedless method. The possible mechanisms proposed by predecessors and the problems needed to be solved are also arranged. Along with this, the important morphological evolution process of AuTNPs during synthesis and post-synthesis stages are revealed, which is of great significance for further understanding the structure of AuTNPs and developing new synthesis strategies. Finally, the applications of AuTNPs, especially associated with plasmonic properties, are listed and summarized where surface-enhanced Raman scattering (SERS), catalysis, phototherapy and biosensor are included, so that researchers can quickly comprehend the current situation, and provide a basis for further development and exploration of AuTNPs.

An Overview of Thrombin Inhibitors in the Perspective of Structureactivity Relationships.

Thrombosis is one of the most important pathogenic factors related to cardiovascular diseases. Presently, thrombin inhibitors have gradually gained prominence in clinical practice due to their unique potential, such as dabigatran. Nevertheless, the risk of bleeding is not completely eliminated, and the threats of gastrointestinal bleeding are even increased in some cases. Therefore, developing new oral thrombin inhibitors with low side effects is urgent. In this paper, we summarized recent advances in the newly synthesized and isolated thrombin inhibitors from 2000 to 2019 and their structure-activity relationships (SARs) along with structure-dependent pharmacokinetic parameters, guiding the next generation of oral thrombin inhibitors.

Enhancement and mechanisms of iron-assisted anammox process.

Anaerobic ammonium oxidation (anammox) is a sustainable biological nitrogen removal technology that has limited large-scale applications owing to the low cell yield and high sensitivity of anammox bacteria (AnAOB). Fortunately, iron-assisted anammox, being a highly practical method could be an effective solution. This review focused on the iron-assisted anammox process, especially on its performance and mechanisms. In this review, the effects of iron in three different forms (ionic iron, zero-valent iron and iron-containing minerals) on the performance of the anammox process were systematically reviewed and summarized, and the strengthening effects of Fe (II) seem to be more prominent. Moreover, the detailed mechanisms of iron-assisted anammox in previous researches were discussed from macro to micro perspectives. Additionally, applicable iron-assisted methods and unified strengthening mechanisms for improving the stability of nitrogen removal and shortening the start-up time of the system in anammox processes were suggested to explore in future studies. This review was intended to provide helpful information for scientific research and engineering applications of iron-assisted anammox.

Encoding Morphogenesis of Quasi-Triangular Gold Nanoprisms with DNA.

Properties of gold nanoparticles vary with their morphologies. Typically, the research on the properties and applications of the nonequilibrium intermediates generated by the morphological evolution of triangular gold nanoprisms is still incomplete. Herein, we employ thiol-DNA (HS-DNA) to protect the low-stability quasi-nanoprisms with different truncation degrees (R values). The presence of HS-DNA not only increases the stability of the quasi-nanoprisms in different microenvironments, but also facilitates us to investigate their intrinsic plasmonic properties related to morphology. Additionally, we serve quasi-nanoprisms loaded with HS-DNA as assembly modules and nanoplatforms for programmable self-assembly higher-order hybrid structures, as well as carriers for encoding and decoding of orthogonal barcode-like information, which opens new opportunities for developing novel building blocks for light manipulation at nanoscale.

Detection techniques of biological and chemical Hall sensors.

Integrated magnetic Hall effect sensors have been widely used in people's daily life over the past decades, and still are gaining enormous attention from researchers to establish novel applications, especially in biochemistry and biomedical healthcare. This paper reviews, classifies, compares and concludes state-of-the-art integrated Hall magnetic sensors in terms of cost, power, area, performance and application. Current applications of the Hall sensors such as detecting magnetic nanoparticles (MNPs) labeled on biomolecule, monitoring blood pulse wave velocity, characterizing soft biological materials, controlling syringe injection rate and eye surgery by training systems, and assisting magnetic resonance imaging (MRI) will be discussed comprehensively and future applications and trends will be highlighted. This review paper will introduce Hall sensor's advantages such as simple design and technology of manufacturing, low cost, low power consumption, possibility of the miniaturizing, noninvasive and room temperature measurement, with respect to the other magnetic sensing systems and methods.

Syntheses and evaluation of daphnetin derivatives as novel G protein-coupled receptor inhibitors and activators.

A series of daphnetin (7,8-dihydroxycoumarin) derivatives 1-22 were synthesized including sixteen new compounds (1-5, 7-14, 18, 21 and 22) and six known compounds (6, 15-17, 19 and 20). Their pharmacological activities on G protein-coupled receptors (GPCRs) were evaluated by double antibody sandwich ELISA (DAS-ELISA) in vitro. Daphnetin derivatives with various substitution patterns/groups were obtained from inhibitors to activators on GPCRs. Derivatives 2-5, 8, 15, 16 and 18-20 possessed moderate activation potency on GPCRs. Among them, derivatives 3-5, 16 and 19 presented significant activation potency on GPCRs with EC50 values in the range of 1.18-1.91 nM. Derivatives 6, 11, 14 and 18 showed significant inhibitory potency on GPCRs with IC50 values in the range of 1.26-1.38 nM. Moreover, the structure-activity relationships (SARs) of daphnetin derivatives were discussed in detail. The new daphnetic-based GPCRs activators and inhibitors have potentials as future drug candidates for the treatment of metabolic diseases.

Novel Bioactive Polyketides Isolated from Marine Actinomycetes: An Update Review from 2013 to 2019.

Marine organism-associated actinobacteria represent a valuable resource for marine drugs due to their abundant secondary metabolites. The special environments in the ocean, for instance, high salt, high pressure, low temperature and oligotrophy, not only adapt to survival of actinomycetes but also enhance molecular diversity of actinomycete secondary metabolites production, thus making marine actinomycetes important sources of marine-based bioactive compounds, especially polyketides. Herein, we summarized the structures and pharmacological activities of polyketides from actinobacteria associated with marine organisms from 2013 to 2019; moreover, the main source species of actinomycetes were discussed as well. We expected that this review would be helpful for future in-depth research and development of marine-based bioactive polyketides.

Structure-Activity Relationships of Natural and Synthetic Indole-Derived Scaffolds as α-Glucosidase Inhibitors: A Mini-Review.

α-Glucosidase plays an important role in carbohydrate metabolism and is an attractive drug target for the treatment of diabetes, obesity and other related complications. Currently, acarbose, miglitol and voglibose have been approved by the FDA for the treatment of diabetes by oral α-glucosidase inhibitors. With the development of anti-diabetic drugs, the emergence of novel drugs with various chemotypes has overshadowed α-glucosidase inhibitors. Since the 1990s, the FDA has not approved new chemical entities against α-glucosidase, which has resulted in restricted clinical medication. Nevertheless, this type of inhibitors possess several unparalleled advantages over other drugs, especially mild side effects (non-systemic gastrointestinal side effects and occasional allergic reactions). Additionally, α-glucosidase inhibitors for monotherapy or in combination with other drugs have been proved to be a feasible approach for the treatment of diabetes. In the last decade, the discovery of natural or synthetic indole derivatives possessing the inhibitory activity of α-glucosidase has received great attention. Herein, we have summarized indoles as inhibitors of α-glucosidase activity, their mechanism of action, synthetic methodologies and structure-activity relationships. Moreover, we have compared the inhibitory potencies of all compounds under their corresponding positive control as well as oral absorption in silico evaluated by tPSA. This review will provide a medium on which future drug design and development for the treatment of diabetes may be modeled as many drug candidates with present great potential as effective anti-diabetic chemotherapy.

Recent Advances on Marine Alkaloids from Sponges.

Alkaloids from marine secondary metabolites have received extensive attention from pharmacists in recent years. Miscellaneous alkaloids derived from marine sponges possessed various pharmacological activities including cytotoxicity, antimicrobial, antioxidant, and so on. Herein, we summarized 149 marine alkaloids from sponges based on their structures and bioactivities reported from 2015 to 2020 and analyzed the production environment of marine sponges with rich alkaloids. Moreover, we discussed biosynthesis routes of pyrrole and guanidine alkaloids from marine sponges Agelas and Monanchora. This article will be beneficial for future research on drugs from marine natural products.

Structure-activity relationship and synthetic methodologies of α-santonin derivatives with diverse bioactivities: A mini-review.

α-Santonin, a sesquiterpene lactone isolated from Artemisia Santonica, possesses diverse bioactivities including antioxidant, anti-inflammation, immunosuppressive, anti-roundworm, anti-malaria, etc. However, its bioactivities are not satisfactory and need to be further optimized. Thus, many α-santonin derivatives were synthesized on the basis of rings A, B and C for the discovery of new analogues with prominent bioactivities. Herein, we reviewed and discussed the related synthetic methodologies, diverse bioactivities and structure-activity relationships (SAR) of α-santonin derivatives.

Syntheses and bioactivities of songorine derivatives as novel G protein-coupled receptor antagonists.

Songorine isolated from Aconitum brachypodum Diels possesses prominent activity of inhibiting G protein-coupled receptors (GPCRs) in the early screening process. In this paper, a series of Songorine derivatives were synthesized and their inhibitory activities on GPCRs were also evaluated by using the Double Antibody Sandwich ELISA (DAS-ELISA) in vitro. Among them, three derivatives (3a, 4, 7) exhibited significant inhibitory activity against GPCRs with IC50 values of 0.08-0.29 nM. Moreover, the structure-activity relationships (SARs) of songorine derivatives were discussed in detail. They have great potentials as novel GPCRs antagonists in the future.