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The study focuses on evaluating the combined effects of quercetin (QCT) and catechin (CAT), both plant-based antioxidants, on alloxan-induced liver toxicity and diabetes in leptin-deficient (Lepob/ob) mice. Diabetes is a metabolic disorder characterized by high blood glucose levels due to inadequate insulin secretion or insulin resistance.

Thirty mice were divided into five groups of 6, including: normal control, diabetic control, diabetic mice treated with 150 mg/kg CAT, diabetic mice treated with 150 mg/kg QCT, and diabetic mice treated with 150 mg/kg CAT, and 150 mg/kg QCT for seven days. Mice were anesthetized after overnight fasting on the 8th day, and the blood sample was collected and the levels of antioxidants and pro-inflammatory factors in serum, and the expression of ADP-ribose polymerase (PARP) protein were measured, and histological studies were performed.

The results showed that diabetic mice receiving QCT and CAT showed lower liver enzymes, fasting blood sugar (FBS), blood urea nitrogen (BUN), creatinine (Cr), cholesterol, triglyceride, low-density lipoprotein (LDL), TNF-α, and thiobarbituric acid reactive substances (TBARS) levels and increased high-density lipoprotein (HDL), total thiol, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels in the liver compared to the ALLO group alone (P<0.001). The level of PARP protein significantly declined in the ALLO group compared to the control group.

The findings of this study demonstrated that QCT, and CAT are reasonably effective in preventing hepatotoxicity and diabetes in mice.

Cisplatin (CPN) is widely used for the management of various malignant tumors.

This study investigated the effects of Thymoquinone (TQN) on the expression of the p62 gene in CPN-induced testicular damage in mice.

Histomorphometry, testis injury scores, expression of p62, and protein levels of LC3-II were assessed.

Cisplatin induced histological changes, increased p62 expression (P < 0.01), and reduced LC3-II levels (P < 0.001). Thymoquinone pretreatment decreased p62 expression while increasing LC3-II protein levels. Thymoquinone significantly reversed the testicular injury scores and improved histomorphometric parameters.

The results indicate that TQN enhances autophagy and improves testicular tissue in CPN-intoxicated mice.

Nervous and brain cells injury is a complex, life-threatening condition that causes mortality and disability worldwide. Noeffective treatment has been clinically verified to date. Achieving effective drug delivery across the blood–brain barrier (BBB) presents a major challenge to therapeutic drug development for nervous and brain cells injury. Furthermore, the field of nerve damage biomarkers is rapidly developing to cope with the many aspects of pathology and enhance clinical management of this type of damage. Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence types of stem cells differentiation. Exosomes are endogenous extracellular vehicles (EVs) containing various biological materials, including lipids, proteins, microRNAs, and other nucleic acids. Compelling evidence exists that Exos, such as stem cell-derived Exos and even neuron or glial cell-derived Exos, are promising treatment strategies for Nervous cells injury because they pass through the BBB and have the potential to deliver molecules to target lesions. Meanwhile, Exos have Fewer safety risks compared to intravenous injection or orthotopic transplantation of viable cells, such as microvascular occlusion or imbalanced growth of transplanted cells. These unique characteristics also make Exos contents, especially Exos-derived microRNAs, as appealing biomarkers in nervous and brain cells injury. In this review, we explore the potential impact of cell-derived Exos and exosome-derived contents on the diagnosis, therapy, and prognosis prediction of nerve damage. The associated challenges and opportunities are also discussed.

Diabetic nephropathy (DN) is a critical complication of diabetes mellitus. This study evaluates whether administration of conditioned medium from kidney tubular cells (KTCs‑CM) has the ability to be efficacious as an alternative to cell‑based therapy for DN.

CM of rabbit kidney tubular cells (RK13; KTCs) has been collected and after centrifugation, filtered with 0.2 filters. Four groups of rats have been utilized, including control, DN, DN treated with CM, and sham group. After diabetes induction by streptozotocin (50 mg/kg body weight) in rats, 0.8 ml of the CM was injected to each rat three times per day for 3 consecutive days. Then, 24‑h urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) have been measured through detection kits. The histopathological effects of CM on kidneys were evaluated by periodic acid–Schiff staining and the expression of microRNAs (miRNAs) 29a and 377 by using the real‑time polymerase chain reaction. The expression of aquapurin‑1 (AQP1) protein was also examined by Western blotting.

Intravenous injections of KTCs‑CM significantly reduced the urine volume, protein 24‑h, BUN, and Scr, decreased the miRNA‑377, and increased miRNA‑29a and AQP1 in DN treated with CM rats.

KTCs‑CM may have the potential to prevent kidney injury from diabetes by regulating the microRNAs related to DN and improving the expression of AQP1.

 Silymarin (SM) has beneficial effects against numerous different types of toxicants. However, the low bioavailability of SM has limited its therapeutic effects.

 This study investigated the toxic effect of nanostructured SM (NSM) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on nephrotoxicity induced by acetaminophen (APAP) in mice.

 The encapsulation of SM in PLGA was performed by the solvent evaporation method. A total of 48 NMRI mice were used in this experimental study. The mice were pretreated with SM or NSM (5 mg/kg) for 7 days, and APAP (300 mg/kg) was administrated on the 6th day. The serum levels of blood urea nitrogen, creatinine, and uric acid were measured. Histological assessment and messenger ribonucleic acid expression of BAX and BCL-2 genes were also carried out.

 The APAP destroyed the structure of the renal tissue and significantly reduced renal weight and glomerulus diameters (P < 0.01). The APAP also caused a significant increase in the serum levels of biochemical markers (P < 0.001) and expression of the BAX/BCL-2 ratio in the renal tissue (P < 0.001). The NSM could improve the renal structure and significantly increase renal weight and glomerulus in the APAP-intoxicated mice. The NSM significantly reduced the level of the biochemical tests and the BAX/BCL-2 ratio in the APAP-treated group (P < 0.01).

 The obtained data indicate that PLGA effectively enhances the nephroprotective effects of SM on nephrotoxicity induced by APAP.

For tissue engineering and clinical translation strategies, it is essential to have a reliable and safe lineage-specific differentiation of stem cells. To deal with several problems caused by growth factor delivery systems and growth factors, exosomes have been used as biomimetic tools to trigger the differentiation of stem cells. It is believed that cell type-specific exosomes can induce lineage-specific differentiation of stem cells. Exosomes trigger cell viability, cell proliferation and differentiation, embryonic implantation, and migration. They have been used successfully in regenerative medicine, such as liver fibrosis, renal diseases, cardiac ischemia, stroke, and skin injuries. The findings highlighted the necessity to take into account the condition and source of exosome donor cells before selecting them for therapeutic use.

One of the severe complications and well-known sources of end stage renal disease (ESRD) from diabetes mellitus is diabetic nephropathy (DN). Exosomes secreted from diverse cells are one of the novel encouraging therapies for chronic renal injuries. In this study, we assess whether extracted exosomes from kidney tubular cells (KTCs) could prevent early stage DN in vivo.

In this experimental, exosomes from conditioned medium of rabbit KTCs (RK13) were purified by ultracentrifuge procedures. The exosomes were assessed in terms of morphology and size, and particular biomarkers were evaluated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Western blot, atomic force microscopy (AFM) and Zetasizer Nano analysis. The rats were divided into four groups: DN, control, DN treated with exosomes and sham. First, diabetes was induced in the rats by intraperitoneial (i.p.) administration of streptozotocin (STZ, 50 mg/kg body weight). Then, the exosomes were injected each week into their tail vein for six weeks. We measured 24-hour urine protein, blood urea nitrogen (BUN), and serum creatinine (Scr) levels with detection kits. The histopathological effects of the exosomes on kidneys were evaluated by periodic acid-Schiff (PAS) staining and expressions of miRNA-29a and miRNA-377 by quantitative real-time polymerase chain reaction (qRT-PCR).

The KTC-Exos were approximately 50-150 nm and had a spherical morphology. They expressed the CD9 and CD63 specific markers. Intravenous injections of KTC-Exos potentially reduced urine volume (P<0.0001), and 24- hour protein (P<0.01), BUN (P<0.001) and Scr (P<0.0001) levels. There was a decrease in miRNA-377 (P<0.01) and increase in miRNA-29a (P<0.001) in the diabetic rats. KTC-Exos ameliorated the renal histopathology with regulatory changes in microRNAs (miRNA) expressions.

KTC-Exos plays a role in attenuation of kidney injury from diabetes by regulating the miRNAs associated with DN.

This research studied the effects of glycyrrhizic acid (GA) on apoptosis induced with by titanium dioxide (NTiO2) in the liver of rats.

It is widely accepted that the contamination resulting from nanoparticles (NPs) is an emerging dangerous issue. Metal oxide nanoparticles have high environmental stability and cause toxicity in the food chain. Thus, the present study investigated the anti-apoptotic effects of glycyrrhizic acid (GA) on the hepatotoxicity generated by titanium dioxide (NTiO2) NPs in the liver tissue.

Thirty-two male Wistar rats were randomly divided into four groups. NTiO2-treated rats were given 300 mg / kg of NTiO2 solution via gavage for 14 days; GA-treated were administered 100 mg/kg GA for 14 days; protection group was pre-treated with GA before NTiO2 administration for 7 days. Then, apoptotic index was evaluated through immunolocalization of Bax and Bcl-2 and TUNEL assay.

we found that HSCORE of Bax expression and apoptotic index experienced a significant increase with NTiO2 (P <0.001), while Bcl-2 expression significantly diminished in NTiO2-treated rats (P <0.001). The results revealed that the increased Bax expression and apoptotic index were reversed by GA and enhanced the activities of Bcl2.

The results revealed that GA effectively attenuated apoptosis against NTiO2 in rats.