Diabetic Rat Model Research Articles

Long-term safety of photobiomodulation exposure to beta cell line and rat islets in vitro and in vivo

This study evaluates the safety and potential benefits of PBM on pancreatic beta cells and islets. PBM was applied to insulin-secreting cell lines (MIN6) and rat pancreatic islets using a 670 nm light source, continuous output, with a power density of 2.8 mW/cm², from 5 s to several 24 h. Measure of cell viability, insulin secretion, mitochondrial function, ATP content, and cellular respiration were assessed. Additionally, a diabetic rat model is used for islet transplantation (pre-conditioning with PBM or not) experiments. Short and long-term PBM exposure did not affect beta cell islets viability, insulin secretion nor ATP content. While short-term PBM (2 h) increases superoxide ion content, this was not observed for long exposure (24 h). Mitochondrial respirations were slightly decreased after PBM. In the islet transplantation model, both pre-illuminated and non-illuminated islets improved metabolic control in diabetic rats with a safety profile regarding the post-transplantation period. In summary, for the first time, long-term PBM exhibited safety in terms of cell viability, insulin secretion, energetic profiles in vitro, and post-transplantation period in vivo. Further investigation is warranted to explore PBM’s protective effects under conditions of stress, aiding in the development of innovative approaches for cellular therapy.

Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits

ABSTRACT As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.

The Influence of Atorvastatin Treatment on Homocysteine Metabolism and Oxidative Stress in an Experimental Model of Diabetic Rats

Objective: In our experimental study, we evaluated the influence of treatment with atorvastatin on the antioxidant activity of intracellular and extracellular systems factors, homocysteine levels (Hcy), and lipid profiles in obese and diabetic rats. Method: Twenty-one male Wistar rats, aged 6 months, 450–550 g, were allocated into three groups. From the beginning of the study, the first group (G-I, control) received only standard food, while the second and third groups (G II—obese, G III—diabetic) were administered a high-fat diet (HFD) with 2% cholesterol. After 2 weeks of accommodation, the specimens in G-III were injected intraperitoneal (i.p.) streptozotocin (35 mg of body weight, pH 4.5), intervention followed by the onset of type 2 diabetes mellitus. Following confirmation of diabetes onset, the specimens in G III were administered concomitantly with the HFD a daily gavage of atorvastatin 20 mg of body weight/day for 20 days. We measured, at the beginning and the end of the study, the Hcy levels, lipid profile, vitamin B12, B6, folic acid, and various parameters of oxidative stress (OS)—total antioxidant status (TAS), glutathione peroxidase (GPX) and superoxide dismutase (SOD). Results: After treatment with atorvastatin, the lipid profile in G III significantly improved compared to the other two groups, but enzymatic markers of oxidative stress did not closely parallel this trend. However, after the treatment of statin, we observed an important reduction in Hcy values. Conclusion: Our results demonstrate that treatment with atorvastatin can be used not only for its lipid-lowering properties and antioxidant effects but also to reduce Hcy concentration in this experimental model of diabetic rats. Moreover, atorvastatin therapy improves lipid profiles, reduces inflammation, suppresses oxidation, and decreases Hcy levels, potentially preventing major adverse cardiovascular events.

The Effects of Melon Superoxide Dismutase and Gliadin on Glutathione Reductase (GSH) and Superoxide Dismutase (SOD) Levels in Blood Plasma and Vitreoretina in Diabetic Rat Model: A Literature Review

The Effects of Melon Superoxide Dismutase and Gliadin on Glutathione Reductase (GSH) and Superoxide Dismutase (SOD) Levels in Blood Plasma and Vitreoretina in Diabetic Rat Model: A Literature Review

Assessment of protective effect of Vitamin E supplementation on oxidative damage of diabetic rat spleen induced by Streptozotocin

AimsIncreased oxidative stress in diabetes mellitus may lead to splenic damage, contributing to decreased immunity. This study aims to evaluate the potential of vitamin E supplements as a protective agent against spleen injury by examining physiological, hematological, biochemical, and histological changes in diabetic rat model. MethodsDiabetes was induced in male wistar albino rats through an intraperitoneal injection of 50mg/kg Streptozotocin, and the rats were randomly divided into five groups. The rats were then administered varying doses of vitamin E for 14 consecutive days. Assessments included renal function tests, blood glucose levels, complete blood counts, lipid profiles, tissue oxidative stress and spleen histology. An acute toxicity study was also conducted on normal rats. ResultsVitamin E supplementation did not result in any mortality up to 5000mg/kg body weight. The treated diabetic group showed improved metabolic characteristics, such as normal body weight, food and water intake and a reduced spleen index compared to the untreated diabetic group. Significant improvements were observed in hematological parameters like packed cell volume (PCV), hemoglobin concentration, RBC (red blood cells) and WBC (white blood cells) counts. HCA (Hierarchical Cluster Analysis) of these parameters indicated that doses of 100mg/kg and 150mg/kg were most similar to normal condition. Catalase and MDA (Malondialdehyde) assays showed a substantial reduction in oxidative stress in spleen tissue and histopathological examination revealed significant regenerative effects. ConclusionThis study demonstrated that vitamin E supplementation significantly enhanced various metabolic, hematological, biochemical, and histological parameters in the diabetic group compared to those who did not receive the treatment. Among the doses tested, 100mg/kg and 150mg/kg body weight were found to yield the most favorable outcomes.

Anti-diabetic and anti-inflammatory activities of Marrubiin isolated from Marrubium vulgare: Indications of its interaction with PPAR γ

BackgroundThe aerial parts of Marrubium vulgare L. were used for many ailments like catarrh to diabetes in many parts of Latin America and Asia. PurposeIdentifying the active principle responsible for anti-diabetic activity of methanol extract of M. vulgare leaves and to predict the possible targets. Study designAll the activity investigations were conducted simultaneously for the extract, fraction, and isolated compounds to decipher the activity profile in comparison to each other which allowed the identification of an active principle followed by use of in silico methods to identify the possible target/s. MethodsThe aerial parts of M. vulgare were extracted using methanol. A chloroform fraction was prepared. Marrubiin and marrubinone B were isolated from this fraction. The anti-hyperglycemic, hypoglycemic, and postprandial blood glucose lowering activities were investigated using streptozotocin-induced diabetic and non-diabetic rat models. Pro-inflammatory cytokine inhibitory potential was investigated using LPS induced acute-inflammatory mouse model and RAW 264.7 cells. Further, antioxidant activity was investigated using a DPPH assay. The in silico analysis, using the Swiss-target prediction tool, was carried out to predict the probable targets of the isolated molecules. ResultsMarrubiin exhibited anti-hyperglycemic effect in diabetic rats followed by hypoglycemia, and postprandial blood glucose lowering in non-diabetic rats. Methanol extract (Mv extract) and chloroform fraction (Mv fraction) showed anti-hyperglycemic and hypoglycemic effects. Moderate inhibition of IL-1β, TNF-α, and IL-6 was observed for marrubiin, marrubinone B, Mv extract, and Mv fraction, in vitro and in vivo. Neither marrubiin nor marrubinone B could quench the DPPH free radicals while Mv extract and Mv fraction could show 80 % suppression. In silico analysis has predicted that marrubiin can interact with PPAR γ but not marrubinone B. ConclusionsMarrubiin and marrubinone B were responsible for the anti-inflammatory effect of Mv extract and Mv fraction while not contributing to the antioxidant effect. Marrubiin was found to be responsible for the anti-diabetic activity of Mv extract. The predicted interaction propensity of marrubiin with PPAR γ could explain its dual activity observed in the experimental setup.

(Pro)renin receptor aggravates myocardial pyroptosis in diabetic cardiomyopathy through AMPK-NLRP3 pathway

IntroductionAs one of the most common complications of diabetes, diabetic cardiomyopathy (DCM) is the main cause of heart failure in patients with diabetes. However, the lack of effective treatments for DCM remains a clinical challenge. (Pro) renin receptor (PRR) is a member of renin angiotensin aldosterone system (RAAS). Here, we aim to determine whether PRR is involved in myocardial pyroptosis in diabetic cardiomyopathy.MethodsWe established diabetic rats model by intraperitoneal injection of streptozotocin (STZ). PRR overexpression adenovirus or PRR knockdown adenovirus was injected into the tail vein. Western blot, histopathology and immunohistochemistry staining, ELISA and Echocardiography were used to detect cardiac function changes and myocardial injury levels of DCM rats. Primary cardiomyocytes were stimulated with high glucose and PRR overexpression or PRR knockdown was achieved by adenovirus transfection, we also used the inhibitor of AMPK to decrease the activity of AMPK. Western blot, Real-time PCR, Immunofluorescence and ELISA were used to detect the level of PRR and pyroptosis in cardiomyocyte.ResultsWe found that high glucose increased the expression of PRR in heart. After overexpression of PRR, the expression of the pyroptosis related proteins such as Caspase-1, IL-1β, IL-18, and NLRP3 was significantly increased, the phosphorylation level of AMPK was significantly decreased, and the fibrosis level was significantly increased, thus aggravating the cardiac function injury of DCM. On the contrary, PRR knockdown can alleviate the level of myocardial pyroptosis in DCM and improve cardiac function. The related mechanism was that PRR could inhibit AMPK phosphorylation and promote the activation of NLRP3 inflammasome.DiscussionPRR aggravated pyroptosis of cardiomyocyte, increased the dysfunction of cardiomyocyte, and may be related to the decrease of AMPK phosphorylation and the overactivation of NLRP3. This may provide new ideas and targets for the treatment of DCM.

GLP-1 receptor agonist liraglutide alleviates kidney injury by regulating nuclear translocation of NRF2 in diabetic nephropathy.

Diabetic nephropathy (DN) is a severe renal disorder that arises as a complication of diabetes. Liraglutide, an analogue of a glucagon-like peptide 1 (GLP-1) receptor agonist, has been shown to decrease diabetes-caused renal damage. Nevertheless, the complete understanding of the roles and mechanism remains unclear. In our study, diabetic rat models were created through a single intraperitoneal injection of streptozotocin (STZ). The level of fasting blood glucose, 24-h urine protein, serum creatinine (Scr) and blood urea nitrogen (BUN) were assessed. Periodic acid-Schiff (PAS) staining was applied to examine the pathological changes in renal tissues. Reactive oxygen species (ROS) formation was measured via dichloro-dihydro-fluorescein diacetate (DCFH-DA) probes. Western blot was conducted to examine the levels of oxidative stress-related and extracellular matrix (ECM)-associated proteins. The nuclear translocation of NRF2 was investigated through immunofluorescence and Western blot assays. We demonstrated that liraglutide attenuated DN-induced oxidative stress and ECM deposition in vitro and in vivo. Liraglutide exerted a reno-protective effect by promoting nuclear translocation of NRF2 in mesangial cells. ML385, an NRF2 inhibitor, counteracted the beneficial impact of liraglutide.

Reduced Graphene Oxide-Substituted Nanohydroxyapatite: Rejuvenating Bone-Nerve Crosstalk with Electrical Cues in a Fragility Fracture Rat Model under Hyperglycemia.

Diabetes has currently acquired the status of epidemic worldwide, and among its various pathological consequences like retinopathy and nephropathy, bone fragility fractures from diabetic osteopathy occurs in later stages and is equally destructive. Chronic hyperglycemia culminates into deteriorating microvasculature and quality of bone, making it prone to fractures. Among these, hip fractures are most common, especially in older diabetic patients apart from underlying neuropathy. Our study is an attempt to ameliorate hip fragility fracture and nerve trauma with electrical stimulation as an interface in a chronic diabetic rat model. We have fabricated reduced graphene oxide-substituted hydroxyapatite as an electroactive bone substitute and incorporated it into chitosan gelatin cryogels. The in situ reduction of graphene oxide during sintering of hydroxyapatite imparts higher potential to the fabricated composite in dealing with problem at question. The cryogels depicted optimum in vitro biocompatibility and enhanced mineralization after ectopic subcutaneous implantation in rats. The therapeutic potency of composite cryogels was evaluated in a hip fracture model with compression to the sciatic nerve in diabetic rats, mimicking the severe clinical trauma. The presence of cryogels in the femoral neck canal coupled with electrical stimulation and biochemical factors significantly improved bone regeneration in diabetic rats as depicted with microcomputed tomography analysis and histology images. The application of electrical stimulation also ameliorated the nerve trauma observed with 70% improvement in electrophysiological parameters such as the compound muscle action potential with combinatorial therapy. We therefore report the successful implication of a multitarget therapy in a chronic diabetic rat model unraveling the bone-nerve crosstalk with electroactive smart cryogels.

Investigating the Phytochemistry and Underlying Glycemic Control Mechanisms of Litchi chinensis Sonn. (Litchi) Peel Ethyl Acetate Extract in a Fructose/Streptozotocin Diabetic Model of Rats

The glycemic control potential and flavonoid profile of litchi have been documented for its hydroalcoholic extracts, while there is scarce information regarding its ethyl acetate extract. This study investigated the flavonoid profile, as well as the ameliorative potential and possible underlying mechanisms of litchi peel ethyl acetate extract on type 2 diabetes-related pathologies in a fructose/streptozotocin (STZ) model of diabetic rats. Sprague Dawley rats were induced with diabetes by administering 10% fructose for 2 weeks and a single i.p. injection of low-dose (40 mg/kg bw) STZ. Thereafter, the animals were orally administered with a low-dose (150 mg/kg bw) and high-dose (300 mg/kg bw) of the peel extract (LDPE and HDPE, respectively) and metformin (200 mg/kg bw). Compared to untreated diabetic rats (AUC = 1004 mg.h/dL), the HDPE significantly (p < 0.05) improved glucose tolerance (AUC = 847 mg.h/dL), which was statistically comparable (p ˃ 0.05) to the effect of metformin (AUC = 903 mg.h/dL). Serum insulin and pancreatic histology data showed that the STZ-induced pancreatic damage and insulin depletion was improved by the HDPE, which could be linked to the observed ameliorative effect of the extract on pancreatic lipid peroxidation and SOD and catalase activity. The extract further improved liver and muscle glycogen storage, as well as muscle hexokinase activity and Akt phosphorylation, suggesting that the extract exerts glycemic control by enhancing glycogen storage and modulating insulin-mediated signaling of glucose uptake and utilization. LC-MS data and documented reports suggest that flavonoids, such as epicatechin, cinnamtannin B2, procyanidin B5, and proanthocyanidin A2, are the possible influencing compounds. The ethyl acetate extract of litchi peel could be a source of bioactive flavonoids that can potentiate glycemic control in diabetes and mitigate oxidative stress-related pathologies.

Effect of Trichosanthes cucumerina Methanol Extract on CRP and Fibrinogen Levels in Diabetic Ulcer Rat Models

Diabetic ulcers can be fatal for people with long-term diabetes. This is caused by the spread of diabetic ulcers and inadequate care for the wound, which can induce an infection and even death. This study aims to determine inflammatory markers, specifically fibrinogen and C-Reactive Protein (CRP), as indicators of healing, particularly in a rat model of diabetic ulcers treated with Trichosanthes cucumerina methanol extract. The methods used were making extracts, measuring blood glucose levels, measuring CRP, and measuring fibrinogen levels in 25 male Wistar rats. Based on the results of glucose and fibrinogen examinations in all groups before treatment and after treatment, it showed a decrease in glucose and fibrinogen levels. Meanwhile, the results of CRP examinations, before and after treatment did not show any differences. The results of statistical analysis showed that there was a significant difference of p<0.05 in pre and post glucose, as well as pre and post fibrinogen.The extract that reduced fibrinogen levels the most was group 3 with 500 mg/KgBW. Meanwhile, CRP levels before and after treatment did not show a decrease.

Extraction, Purification, Characterization, and Wound Healing Effects of Novel Prickly Pear (Opuntiaficus-indica (L.) Mill.) Heteropolysaccharides

Background: The present study undertakes the purification of a novel polysaccharide from Tunisian prickly pear (Opuntiaficus-indica (L.) Mill.) rackets (PPPRs) and the determination of its physicochemical properties, structure, antibacterial and antioxidant properties, as well as its in vitro and in vivo wound healing potential. Methods: The PPPR was structurally analyzed by Fourier Transform Infrared Spectroscopy (FTIR) and UV/Visible Spectroscopy, revealing characteristic bands of polysaccharides. According to thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and Gas Chromatography–Mass Spectrometry (GC–MS) analyses. Results: The crude PPPR is an heteropolysaccharide composed of glucose (62.4%), galactose (19.37%), mannose (10.24%), and rhamnose (7.98%), with an average molecular weight of 90.94 kDa. This novel polysaccharide exhibited notable antioxidant potential assessed by four different in vitro assays: the 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, ferric reducing power, ferrous chelating activity, and scavenging activity against 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS). In addition, the PPPR displayed high antibacterial activities with a MIC of 2.5 mg/mL against Salmonella Typhimurium and Pseudomonas aeruginosa, cytocompatibility properties, and non-cytotoxicity. Subsequently, the effect of the PPPR on skin wound healing was studied in a diabetic rat model induced by alloxan, revealing a significant acceleration in the wound healing process. This acceleration was evidenced by the expedited recovery of the dermis, increased formation of blood vessels, and enhanced tissue granulation. Conclusion: Therefore, the findings offer fresh perspectives on the creation of a potentially efficient and promising racket polysaccharide-based therapy for the treatment of persistent diabetic wounds.

Niclosamide attenuates erectile dysfunction and corporal fibrosis via reversal of Smad signaling in diabetic rat model.

Diabetes mellitus-induced erectile dysfunction (DMED) is a common urological complication of diabetes, and current drugs often fail to provide an effective treatment. Smad2/3 signaling-mediated corporal fibrosis has a critical role in the molecular basis of DMED. We investigated the effect of Niclosamide (Nic), an antihelmintic drug with antifibrotic effects, on erectile function in a rat DMED model. Male Sprague Dawley rats were injected intraperitoneally (i.p) with streptozotocin (75mg/kg) to induce diabetes. At week 8, both diabetic and nondiabetic rats were treated with Nic (10mg·kg-1/day; i.p) or vehicle for 4weeks. At week 12, erectile function was evaluated as intracavernous pressure (ICP) response to the electrical stimulation of the cavernous nerve (CN). Penile tissues were harvested for Masson's trichrome staining or western blotting to determine corporal fibrosis and Smad2/3 pathway-related protein expression, respectively. At the end of the experimental protocol, in vivo erectile function was assessed by measuring the ratio of ICP/ mean arterial pressure (MAP) and total ICP following CN stimulation. Smooth muscle content and collagen fibers were evaluated by Masson's trichrome staining of the penile tissues. The expressions of fibrosis-related proteins (Smad2, Smad3, fibronectin) were determined using western blotting in the penile tissues. Erectile function, as determined by the maximum ICP/MAP and total ICP/MAP ratios, was drastically decreased in diabetic rats. Corporal tissues of diabetic rats were severely fibrotic with a significant increase in collagen fibers and a marked reduction in smooth muscle content. Also, the protein expressions of phosphorylated (p-)Smad2, p-Smad3 and fibronectin were significantly increased in the penis of diabetic rats. Both functional and molecular alterations in DMED were effectively reversed by Nic-treated diabetic rats without a glycemic alteration. Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects. The present study provides the first evidence that Nic has beneficial effect on erectile dysfunction by attenuating corporal fibrosis in a rat model of DMED. The effect of Nic on penile endothelial function and the other potential underlying mechanisms needs to be further elucidated. Nic improved erectile function in DMED rats possibly suppressing penile fibrosis by inhibiting Smad2/3 signaling. These results suggest a potential therapeutic repurposing of Nic as an adjuvant treatment in DMED.

Effect of cuproptosis on acute kidney injury after cardiopulmonary bypass in diabetic patients

BACKGROUND Cardiopulmonary bypass (CPB) is a common procedure in cardiac surgery. CPB is a high-risk factor for acute kidney injury (AKI), and diabetes is also such a factor. Diabetes can lead to copper overload. It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload. AIM To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis. METHODS Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB. Levels of copper ion, lactate, glucose, heat shock protein-70 (HSP-70), and dihydrolipoamide dehydrogenase (DLAT) were determined. A diabetic rat model was established and CPB was performed. The rats were assessed for the development of CPB-AKI, and for the association of AKI with cuproptosis by detecting copper levels, iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy. RESULTS CPB resulted in elevations of copper, lactate, HSP-70 and DLAT in blood and urine in both diabetic and non-diabetic patients. CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats. Cuproptosis-related proteins also appeared to be significantly reduced. CONCLUSION CPB-AKI is associated with cuproptosis. Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.

Wireless, Programmable, and Refillable Hydrogel Bioelectronics for Enhanced Diabetic Wound Healing.

Diabetic wounds, characterized by complex pathogenesis and high infection rates, pose significant challenges in treatment due to prolonged recovery times and high recurrence rates, often leading to severe complications such as amputation and death. Traditional dry dressing treatments fail to address the unique microenvironment of diabetic wounds and tend to cause secondary damage due to frequent replacement. In this study, an electronic-embedding, drug-loading hydrogel bioelectronics is reported for accelerating diabetic wound healing using a combination of programmable pharmaceutical and electrostimulative approaches. Encapsulated in stretchable and biocompatible materials, this device is capable of multiple drug refilling and accelerated drug release modulated by on-board electronics. In vivo experiments on diabetic model rats confirm the device's effectiveness in promoting wound healing. This innovative approach implies the potential for improving diabetic wound management using a combination of physical, material, and pharmaceutical interventions.

Ferric Iron/Shikonin Nanoparticle-Embedded Hydrogels with Robust Adhesion and Healing Functions for Treating Oral Ulcers in Diabetes.

Oral ulcers can be addressed using various biomaterials designed to deliver medications or cytokines. Nevertheless, the effectiveness of these substances is frequently limited in many patients due to poor adherence, short retention time in the mouth, and less-than-optimal drug efficacy. In this study, a new hydrogel patch (FSH3) made of a silk fibroin/hyaluronic acid matrix with light-sensitive adhesive qualities infused with ferric iron/shikonin nanoparticles to enhance healing effects is presented. Initially, this hydrogel forms an adhesive barrier over mucosal lesions through a straightforward local injection, solidifying when exposed to UV light. Subsequently, FSH3 demonstrates superior reactive oxygen species elimination and near-infrared photothermal bactericidal activity. These characteristics support bacterial elimination and regulate oxidative levels, promoting a wound's progression from inflammation to tissue regeneration. In a diabetic rat model mimicking oral ulcers, FSH3 significantly speeds up healing by adjusting the inflammatory environment of the injured tissue, maintaining balance in oral microbiota, and promoting faster re-epithelialization. Overall, the light-sensitive FSH3 hydrogel shows potential for rapid wound recovery and may transform therapeutic methods for managing oral ulcers in diabetes.

Zinc-based Polyoxometalate Nanozyme Functionalized Hydrogels for optimizing the Hyperglycemic-Immune Microenvironment to Promote Diabetic Wound Regeneration.

In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial. Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process. Therefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds.

"Evaluation of the effects of pioglitazone on perivascular adipose tissue function, properties and structure in a rat model of type-2 diabetes."

Perivascular adipose tissue (PVAT) plays an important role in many physiological and pathological processes, such as regulation of vascular tone. The aim of this study is to evaluate the effects of pioglitazone on functional, structural, and biochemical properties of PVAT in an experimental model of type-2 diabetes (T2DM). T2DM was induced by high-fat-diet/low-dose-streptozotocin (HFD/STZ) in rats, and pioglitazone (20mg/kg/p.o.) was administered for 6 weeks. Changes in biochemical parameters, PVAT-mass, vascular-reactivity in thoracic-aorta as well as PVAT adipocytokine and PPARG-expression levels, and histopathology were evaluated. Pioglitazone administration improved blood glucose and lipid profiles in T2DM. Pioglitazone did not change the anticontractile effect of PVAT on aortic contractile reactivity and besides, had no influence on endothelium-dependent and -independent relaxation responses. Pioglitazone administration increased PVAT-mass and TNF-α levels while adiponectin, leptin, and IL-6 levels were unchanged. Also, a prominent increase was observed in PPARG-expression in T2DM-Pio group. Moreover, pioglitazone decreased liver steatosis, aortic wall thickening and myocardial damage whereas increased adipocyte size and adiposity in PVAT. Overall, pioglitazone treatment changed the mass and in part the inflammatory profile of PVAT but did not modify vasoreactivity in T2DM. This study provides novel findings in relationship with the adipogenic effect of pioglitazone and PVAT function.

Antioxidant effects of a novel pioglitazone analogue (PA9) in a rat model of diabetes: Modulation of redox homeostasis and preservation of tissue architecture

Oxygen-free radicals have been implicated in the initiation of diabetic complications. Thiazolidinediones (TZDs), known for their antidiabetic properties, also demonstrate notable antioxidant and anti-inflammatory effects. Although a recently developed imidazolyl analogue of pioglitazone (PA9) has exhibited superior glucose-lowering efficacy compared to pioglitazone, its antioxidant effects remain unexplored. Thus, the objective of this study is to evaluate the antioxidant properties of PA9 in animal models with diabetes.Rats were randomly separated into the following four groups: control, diabetic, and two groups treated orally with pioglitazone as a standard drug and PA9 for ten days. Upon completion of the experiment, tissues from the liver, heart, brain, pancreas, spleen, and kidneys were collected to assess oxidant/antioxidant markers and histological alterations. The administration of PA9 resulted in a noteworthy reduction in malondialdehyde (MDA) levels compared to the diabetic group (p < 0.05). The group receiving PA9 displayed elevated levels of three antioxidant markers, catalase (CAT), superoxide dismutase (SOD), and total thiol, in pancreatic tissue compared to diabetic rats (p < 0.05).Furthermore, increased content of CAT was evident in the heart (p < 0.05), spleen (p < 0.001), brain, and kidney tissues in the PA9-treated group, along with augmented thiol content in the spleen compared to the diabetic group. Remarkably, no significant histological changes were observed in the liver, pancreas, heart, brain, spleen, and kidneys of the PA9-treated groups relative to diabetic rats. PA9 effectively mitigates oxidative stress, modulates redox homeostasis, and shows promise in preventing diabetic complications. The proven safety profile of this analogue underscores its potential, warranting comprehensive clinical evaluation to thoroughly understand its therapeutic scope and efficacy in the management of diabetes.

Efficacy of Oral Nanoparticle-Encapsulated Insulin in Reducing Oxidative Stress and Enhancing Tissue Integrity in a Diabetic Rat Model.

Diabetes mellitus, a chronic metabolic disorder, leads to systemic organ damage characterized by oxidative stress and structural alterations, contributing to increased morbidity and mortality. Traditional subcutaneous insulin therapy, while managing hyperglycemia, often falls short in addressing the oxidative damage and preventing organ-specific complications. This study evaluates the therapeutic efficacy of a novel oral nanoparticle-mediated insulin (nCOF/Insulin) against these diabetes-induced changes, comparing it with traditional subcutaneous insulin in a streptozotocin (STZ)-induced diabetic rat model. We induced diabetes in Wistar rats, dividing them into four groups: standard control, diabetic control, diabetic treated with subcutaneous insulin, and diabetic treated with oral nanoparticle-mediated insulin (nCOF/Insulin). Assessments included organ and body weights, histopathological examinations, and oxidative stress markers (MDA and PCOs) across various organs, including the brain, muscle, intestine, spleen, heart, liver, kidney, and adrenal glands. Additionally, we evaluated antioxidant parameters (GSH and catalase) and conducted immunohistochemical analysis of E-cadherin to assess intestinal integrity. Our findings reveal that STZ-induced diabetes significantly impacts organ health, with subcutaneous insulin providing limited mitigation and, in some cases, exacerbating oxidative stress. Conversely, oral nCOF/Insulin treatment effectively restored organ and body weights, reduced oxidative stress markers, and mitigated histological damage. This suggests that oral nCOF/Insulin not only offers superior glycemic control but also addresses the underlying oxidative stress. nCOF/Insulin emerges as a promising treatment for diabetes, with the potential to improve patient quality of life by ameliorating oxidative stress and preventing organ-specific complications. This study underscores the need for further investigation into the long-term effects and mechanisms of action of oral nCOF/Insulin, aiming to revolutionize diabetes management and treatment strategies.