Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. With the rising prevalence of diabetes, the occurrence of DN is likely to hit pandemic proportions. The current treatment strategies employed for DN focus on the management of blood pressure, glycemia, and cholesterol while neglecting DN’s molecular progression mechanism. For many theranostic uses, nano-technological techniques have evolved in biomedical studies. Several nanotechnologically based theranostics have been devised that can be tagged with targeting moieties for both drug administration and/or imaging systems and are being studied to identify various clinical conditions. The molecular mechanisms involved in DN are discussed in this review to assist in understanding its onset and progression pattern. We have also discussed emerging strategies for establishing a nanomedicine-based platform for DN-targeted drug delivery to increase drug’s efficacy and safety, as well as their reported applications.
1 January 2019 in Brazilian Journal of Medical and Biological Research
This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.
Liver cirrhosis is one of the most prevalent chronic liver disorders with high mortality. We aimed to explore changed gut microbiome and urine metabolome in compensatory liver cirrhosis (CLC) patients, thus providing novel diagnostic biomarkers for CLC. Forty fecal samples from healthy volunteers (control: 19) and CLC patients (patient: 21) were undertaken 16S rDNA sequencing. Chromatography-mass spectrometry was performed on 40 urine samples (20 controls and 20 patients). Microbiome and metabolome data were separately analyzed using corresponding bioinformatics approaches. The diagnostic model was constructed using the least absolute shrinkage and selection operator regression. The optimal diagnostic model was determined by five-fold cross-validation. Pearson correlation analysis was applied to clarify the relations among the diagnostic markers. 16S rDNA sequencing analyses showed changed overall alpha diversity and beta diversity in patient samples compared with those of controls. Similarly, we identified 841 changed metabolites. Pathway analysis revealed that the differential metabolites were mainly associated with pathways, such as tryptophan metabolism, purine metabolism, and steroid hormone biosynthesis. A 9-maker diagnostic model for CLC was determined, including 7 microorganisms and 2 metabolites. In this model, there were multiple correlations between microorganisms and metabolites. Subdoligranulum, Agathobacter, norank_f_Eubacterium_coprostanoligenes_group, Butyricicoccus, Lachnospiraceae_UCG_004, and L-2,3-Dihydrodipicolinate were elevated in CLC patients, whereas Blautia, Monoglobus, and 5-Acetamidovalerate were reduced. A novel diagnostic model for CLC was constructed and verified to be reliable, which provides new strategies for the diagnosis and treatment of CLC.
22 September 2025 in Journal of Controlled Release
The current study presents two patients who lived in a rural family with close contact and suffered from rapidly progressive pneumonia. Chest computed tomography images and lymphocytopenia indicate...