Chemico-biological Interactions

Methylglyoxal (MGO) is an endogenous, highly reactive dicarbonyl metabolite generated under hyperglycaemic conditions. MGO plays a role in developing pathophysiological conditions, including diabetic cardiomyopathy. However, the mechanisms involved and the molecular targets of MGO in the heart have not been elucidated. In this work, we studied the exposure-related effects of MGO on cardiac function in an isolated perfused rat heart ex vivo model. The effect of MGO on calcium homeostasis in cardiomyocytes was studied in vitro by the fluorescence indicator of intracellular calcium Fluo-4...

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by complex clinical symptoms and multi-organ damage. One of the most prevalent complications of SLE is lupus nephritis (LN). Rutin, a natural flavonoid compound found in various plants used in traditional Chinese medicine, has shown promising anti-inflammatory, antioxidant, and renal protective effects. In our study, we treated MRL/lpr mice, a model known for spontaneously developing LN, with Rutin. Our findings reveal that Rutin markedly reduced serum cytokine and autoantibody levels and decreased inflammatory cell infiltration in renal tissues, thereby ameliorating kidney pathology...

TGF-β/Smad signaling pathway plays an important role in the pathogenesis and progression of liver fibrosis. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+) dependent enzyme and responsible for deacetylating the proteins. Increasing numbers of reports have shown that the molecular mechanism of SIRT1 as an effective therapeutic target for liver fibrosis but the transformation is not very clear. In the present study, liver fibrotic tissues were screened by staining with Masson, hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) for histopathological observation from the liver biopsy of seventy-seven rhesus monkey, which fixed with 4% paraformaldehyde (PFA) after treatment with high-fat diet for two years...

RNA plays an important role in many biological processes which are crucial for cell survival, and it has been suggested that it may be possible to inhibit individual processes involved in many diseases by targeting specific sequences of RNA. The aim of this work is to determine the affinity of novel 3,9-disubstited acridine derivative 1 with three different RNA molecules, namely single stranded poly(rA), double stranded homopolymer poly(rAU) and triple stranded poly(rUAU). The results of the absorption titration assays show that the binding constant of the novel derivative to the RNA molecules was in the range of 1...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) protein aggregates, leading to synaptic dysfunction and neuronal cell death. In this study, we used a comprehensive approach encompassing in vitro assays, computational analyses, and an in vivo Caenorhabditis elegans model to evaluate the inhibitory effects of various xanthones, focusing on Garcinone D (GD), on Aβ42 oligomer formation. Dot blot analysis revealed concentration-dependent responses among xanthones, with GD consistently inhibiting Aβ42 oligomer formation at low concentrations (0...

Nickel (Ni) and its compounds are common, widely distributed components of hazardous waste in the chemical industry. Excessive exposure to Ni can cause kidney damage in humans and animals. We investigated the impact of Ni on renal mitochondria using in vivo and in vitro models of Ni nephrotoxicity, and explored the Ni nephrotoxic mechanism. We showed that nickel chloride (NiCl2 ) damaged the renal mitochondria, causing mitochondrial swelling, breakage of the mitochondrial cristae, increased levels of mitochondrial reactive oxygen species (mt-ROS), and depolarization of the mitochondrial membrane potential (MMP)...

It is widely accepted that humans are constantly exposed to micro-plastics and nano-plastics through various routes, including inhalation of airborne particles, exposure to dust, and consumption of food and water. It is estimated that humans may consume thousand to millions of micro-plastic particles, equating to several milligrams per day. Prolonged exposure to micro-plastics and nano-plastics has been linked to negative effects on different living organisms, including neurotoxicity, gastrointestinal toxicity, nephrotoxicity, and hepatotoxicity, and developmental toxicities...

The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe2 O4 ) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V5+ centres...

It is well-established that the reduced Memory B cells (MBCs) play an important role in the pathogenesis of ulcerative colitis (UC), rendering them a potential therapeutic target for UC intervention. Astragalus polysaccharide (APS), a primary active constituent derived from the classic traditional Chinese medicine Astragalus membranaceus (AM), has been used for centuries in the treatment of UC in both human and animal subjects due to its renowned immunomodulatory properties. However, it is unknown whether APS can regulate MBCs to alleviate experimental colitis...

Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study...

Layered double hydroxides nanoparticles (LDH-NP) are increasingly studied for biomedical applications. Nevertheless, their interaction with biomolecules such as proteins needs further exploration for an effective application. In this work, the adsorption of bovine serum albumin (BSA) on LDH-NP and the conformation changes of the protein upon adsorption were characterized using fluorescence spectroscopy. First, the quenching of tryptophan residues of BSA by chloride-intercalated LDH-NP was explored and the BSA adsorption capacity of LDH-NP were determined...

Selective Androgen Receptor Modulators (SARMs), particularly (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic-acid-methyl-ester (YK11), are increasingly popular among athletes seeking enhanced performance. Serving as an Androgen Receptor (AR) agonist, YK11 stimulates muscle growth while inhibiting myostatin. Our study delved into the impact of YK11 on the rat hippocampus, analyzing potential alterations in neurochemical mechanisms and investigating its synergistic effects with exercise (EXE), based on the strong relationship between SARM users and regular exercise...

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC)...

Ferroptosis is a form of programmed cell death involved in various types of acute kidney injury (AKI). It is characterized by inactivation of the selenoprotein, glutathione peroxidase 4 (GPX4), and upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). Since urinary selenium binding protein 1 (SBP1/SELENBP1) is a potential biomarker for AKI, this study investigated whether SBP1 plays a role in AKI. First, we showed that SBP1 is expressed in proximal tubular cells in normal human kidney, but is significant downregulated in cases of AKI in association with reduced GPX4 expression and increased ACSL4 expression...

Liver regeneration after liver tumor resection or liver transplantation is crucial, the remaining liver frequently fails to regenerate in some patients. Oleanolic acid (OA), a pentacyclic triterpenoid compound which has been shown to protect against various liver diseases. However, the effect of OA on liver regeneration after partial hepatectomy (PHx) is still unclear. In this study, the results showed that OA (50 mg/kg, twice daily) treatment induced liver mass restoration and increased the liver-to-body weight ratio of mice following PHx...

Huntington's disease (HD) is an inheritable autosomal-dominant disorder that targets mainly the striatum. 3-Nitropropionic acid (3-NP) induces obvious deleterious behavioral, neurochemical, and histological effects similar to the symptoms of HD. Our study aimed to examine the neuroprotective activity of tropisetron, an alpha-7 neuronal nicotinic acetylcholine receptor (α-7nAChR) agonist, against neurotoxic events associated with 3-NP-induced HD in rats. Forty-eight rats were randomly allocated into four groups...

Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, such as Olaparib, have been pivotal in treating BRCA-deficient ovarian cancer. However, their efficacy is limited in over 40% of BRCA-deficient patients, with acquired resistance posing new clinical challenges. To address this, we employed bioinformatics methods to identify key genes impacting Olaparib sensitivity in ovarian cancer. Through comprehensive analysis of public databases including GEO, CPTAC, Kaplan Meier Plotter, and CCLE, we identified CRABP2 as significantly upregulated at both mRNA and protein levels in ovarian cancer, correlating with poor prognosis and decreased Olaparib sensitivity...

The current study imposes a new class of organophosphorus (OP)-inhibited cholinesterase reactivators by conceptualizing a family of asymmetric bisoximes with various reactivating scaffolds. Several novel nucleophilic warheads were investigated, putting forward 29 novel reactivating options, by evaluating their nucleophilicity and ability to directly decompose OP compounds. Adopting the so-called zwitterionic strategy, 17 mono-oxime and nine bisoxime reactivators were discovered with major emphasis on the bifunctional-moiety approach...

Aucubin (AU), an iridoid glycoside extracted from Eucommia ulmoides, exerts anti-osteoporotic effects by promoting osteogenesis, as reported in previous studies. Here, we investigated the effects of AU under mechanical stretch stress. MC3T3-E1 cells were treated with dexamethasone (DEX) in vitro and subjected to mechanical stretch stress to establish an osteoporotic orthodontic force cell model. AU treatment increased the mRNA and protein expressions of BMP2, OPN, RUNX2, COL-1 and other osteogenic differentiation factors in MC3T3-E1 cells...

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc...