Diabetic Rat Model Research Articles

The Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Liraglutide Regulates Sirtuin-1-Mediated Neutrophil Extracellular Traps to Improve Diabetes-Induced Bone Metabolism Imbalance

Background: Diabetes mellitus (DM) is a chronic metabolic disorder that disrupts normal bone remodeling. Objectives: This study aimed to investigate how the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LIR) addresses bone metabolism imbalances induced by type-II diabetes. Methods: Type-II diabetic rat models were established through a single intraperitoneal injection of streptozotocin (STZ). Blood glucose levels were measured using a blood glucose meter, and insulin levels were assessed using an assay kit. Bone formation markers [alkaline phosphatase (ALP), osteocalcin (OCN), and procollagen I N-terminal propeptide (PINP)] and bone resorption markers [tartrate-resistant acid phosphatase (TRACP) and CTX-1] were monitored using assay kits. Bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro under high-fat and high-glucose (HFHS) conditions to mimic diabetic bone metabolism dysregulation. Neutrophil extracellular traps (NETs) formation was examined through immunofluorescent staining and Western blot analysis. Results: Liraglutide was found to reduce STZ-induced NETs formation, as indicated by decreased expression of cit-H3 by 36.90% - 53.57%, myeloperoxidase (MPO) by 55.81% - 65.12%, NE by 53.95% - 65.17%, and PAD4 by 46.81% - 63.83%, alongside increased Sirtuin-1 (SIRT1) expression in femur tissue (70.71% - 91.19%). In vitro, LIR enhanced osteogenesis and inhibited apoptosis, effects that were partially reversed by SIRT1 knockdown. Additionally, SIRT1 knockdown partially restored LIR-induced reductions in oxidative stress, inflammation, and NETs formation. Conclusions: LIR mitigates diabetes-induced bone metabolism imbalance by inhibiting NETs formation through SIRT1 mediation.

Effect of moderate-intensity aerobic exercise on bladder TGF-β1 and type I collagen expressions in diabetic rat model

Transforming growth factor-beta 1 (TGF-β1) and type I collagen play crucial roles in the pathogenesis of diabetic bladder disease (DBD). Moderate-intensity aerobic exercise increases antioxidant activity to help manage DBD. The aim of this study was to evaluate the effect of moderate-intensity aerobic exercise on the expression of TGF-β1 and type I collagen in the detrusor and lamina propria of the bladder in a type 2 diabetes mellitus (T2DM) rat model. A true experimental design with a post-test-only control group design was conducted with white rats (Rattus norvegicus), divided into three groups: a T2DM model group sacrificed after T2DM induction and diagnosed with T2D from a fasting blood glucose (FBC) test (Group C), a T2DM model group that did not receive exercise (Group NE), and a T2DM model group that received moderate-intensity aerobic exercise (Group E). Moderate-intensity aerobic exercise was conducted over six weeks, with a frequency of five days per week for 60 minutes per session. The findings revealed a significant reduction in TGF-β1 expression in the lamina propria in Group E compared to Group C (p=0.004) Additionally, both Group E (p=0.002) and Group NE (p=0.028) showed a significant reduction in type I collagen expression in the lamina propria compared to Group C. These findings provide a basis for further investigation regarding the mechanism of non-pharmacologic DBD management by employing moderate-intensity exercise.

DESIGN, SYNTHESIS, AND BIO PROFILING OF 2, 3-DIHYDROQUINAZOLIN-4(1H)-ONE DERIVATIVE AS TYPE II DIABETES AGENTS: A COMPREHENSIVE IN SILICO, IN VITRO, AND IN VIVO STUDY

Objective: Diabetes mellitus is a significant global health challenge, with Type 2 Diabetes Mellitus (T2DM) being a leading cause of mortality worldwide, demanding the need for effective interventions by developing innovative therapeutic strategies or novel antidiabetic agents. This study explores in silico, in vitro, and in vivo approaches to identify the most potent 2,3-Dihydroquinazolin-4(1H)-One derivative molecule with antidiabetic activity. Methods: Eleven new derivatives were designed, studied in silico to identify the most promising compounds, synthesized, studied spectrally to describe them, and evaluated for both in vitro and in vivo investigations. Alpha amylase and alpha-glucosidase inhibitory activities were investigated in vitro. The endogenous suppression of glucose synthesis in Hepatoblastoma cell line 2(HepG2) cells and the in vitro glucose absorption assay on cultivated L6 cell lines were conducted. To assess the ability of the newly synthesized compounds to prevent diabetes, in vivo investigations were conducted on Streptozotocin (STZ)-induced diabetic rats and the effects on various biochemical parameters were identified.Results: Leveraging computational methods, the QZ9 molecule was identified with stable interactions with key biomolecules associated with T2DM. Subsequent in vitro assays confirmed the inhibitory effects of QZ2, QZ8, and QZ9 on alpha-amylase and alpha-glucosidase activities, suggesting their potential as enzyme inhibitors. Additionally, QZ8 and QZ9 demonstrated enhanced glucose uptake and production inhibition in HepG2 cells, indicating their role in improving glucose homeostasis. In vitro, the top-ranked molecules QZ2, QZ8, and QZ9 were analyzed to validate the in silico findings and assess their potential as therapeutic agents for T2DM. The inhibition of α-amylase activity by QZ2, QZ8, and QZ9 was dose-dependent, with maximum inhibition observed at 1000 µg/ml: 57.33% for QZ2, 52.21% for QZ8, and 87.16% for QZ9. Similarly, α-glucosidase inhibition at 1000 µg/ml was 59.96% for QZ2, 53.50% for QZ8, and 81.51% for QZ9. Both QZ8 and QZ9 significantly increased glucose uptake and inhibited glucose production in HepG2 cells, with maximum glucose production inhibition at 100 µg/ml: 62.22% for QZ8 and 62.35% for QZ9. These findings suggest that QZ8 and QZ9 contribute to glucose homeostasis. QZ9 demonstrated superior enzyme inhibition compared to QZ2 and QZ8, with α-amylase and α-glucosidase inhibition up to 87.16% and 81.51%, respectively, at 1000 µg/ml. In vivo investigations in Diabetic rat models further confirmed the efficacy of these compounds by showing significant reductions in blood glucose levels. These results suggests the potentiality of QZ9 as a promising novel Antidiabetic agent.Conclusion: Combining computational predictions with experimental validations, this integrated approach highlights the promise of 2,3-Dihydroquinazolin-4(1H)-One derivative QZ9 as a novel antidiabetic agent, warranting further investigation for clinical translation.

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.

Unraveling the impact of semaglutide in a diabetic rat model of testicular dysfunction: Insights into spermatogenesis pathways and miRNA-148a-5p

Unraveling the impact of semaglutide in a diabetic rat model of testicular dysfunction: Insights into spermatogenesis pathways and miRNA-148a-5p

Hydrogen sulfide alleviates neural degeneration probably by reducing oxidative stress and aldose reductase expression.

We investigated the potential role of hydrogen sulfide (H2S) as a novel therapy for diabetic peripheral neuropathy in diabetic rats. A single dose of streptozotocin (60 mg/kg) was applied to the rats for the diabetic rat models. Sodium bisulfide (50 μmol/kg/d) was injected intraperitoneally daily for 2 weeks as H2S treatment. Electromyogram, haematoxylin eosin staining, transmission electron microscopy, western blotting and enzyme-linked immunosorbent assay were then performed. H2S treatment did not affect body weights, blood glucose levels or liver function of diabetic rats, while the creatine levels of the H2S-treated diabetic rats decreased compared with the diabetic control rats. H2S treatment for 2 weeks did not affect the sciatic nerve conduction velocity of the diabetic rats. However, H2S treatment relieved neurons loss and cell atrophy of dorsal root ganglion, and axon degeneration of sciatic nerve in diabetic rats. Serum super oxide dismutase (SOD) levels and SOD2 levels in the sciatic nerve of diabetic rats were lower than the non-diabetic rats but were restored after H2S treatment. Serum and sciatic nerve homogenate malondialdehyde and aldose reductase expression were higher in diabetic rats but decreased significantly after H2S treatment. Our study revealed that H2S alleviates neural degeneration in diabetic rats probably by reducing oxidative stress and downregulating aldose reductase expression.

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

As 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. We 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. We 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. PRR 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&lt;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.