A supercritical fluid co-extract of turmeric powder and dried coconut shreds shows neuroprotection against AlCl3-induced Alzheimer's disease in rats through nose to brain delivery.

This study was aimed at investigating the neuroprotective potential of a co-extract obtained by supercritical fluid extraction (SFE) of turmeric powder and dried coconut shreds against aluminium chloride (AlCl3)-induced Alzheimer's disease (AD) in male Wistar rats. Fifty animals were allocated to five groups, which received saline (vehicle control, group 1), a combination of saline and aluminium chloride (AlCl3) (disease control, group 2), coconut oil (COO) (SFE extracted, treatment group 3), turmeric oleoresin (Cur) (SFE extracted, treatment group 4) and SFE co-extract of turmeric powder and coconut shreds (CurCOO) (treatment group 5). Animals were subjected to behavioural evaluation. In addition, the hippocampal section of the brain from all groups was subjected to biochemical, molecular and histopathological evaluations. The results showed CurCOO administered intranasally improved cognitive abilities, reversed histological alterations in the brain, reduced hippocampus inflammation studied through proinflammatory cytokine markers like TNF-α and IL-6 as compared to the disease control group. The impact of CurCOO on preventive neurodegeneration was also observed through a reduction in protein transcription factor NF-kB in the treated group 5 as compared to a disease control group. The effect of intranasal delivery of CurCOO on the neurons responsible for memory consolidation was evident from low acetylcholinesterase (AChE) enzyme activity in the treated groups with respect to AlCl3 induced group. Summarily, the results demonstrated intranasal delivery of CurCOO to show better efficacy than Cur and COO in preventing neurodegeneration associated with AlCl3 induced Alzheimer's disease.

Uncovering the Significance of STEP61 in Alzheimer's Disease: Structure, Substrates, and Interactome.

STEP (STriatal-Enriched Protein Tyrosine Phosphatase) is a brain-specific phosphatase that plays an important role in controlling signaling molecules involved in neuronal activity and synaptic development. The striatum is the main location of the STEP enzyme. An imbalance in STEP61 activity is a risk factor for Alzheimer's disease (AD). It can contribute to the development of numerous neuropsychiatric diseases, including Parkinson's disease (PD), schizophrenia, fragile X syndrome (FXS), Huntington's disease (HD), alcoholism, cerebral ischemia, and stress-related diseases. The molecular structure, chemistry, and molecular mechanisms associated with STEP61's two major substrates, Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAr) and N-methyl-D-aspartate receptors (NMDARs), are crucial in understanding the relationship between STEP61 and associated illnesses. STEP's interactions with its substrate proteins can alter the pathways of long-term potentiation and long-term depression. Therefore, understanding the role of STEP61 in neurological illnesses, particularly Alzheimer's disease-associated dementia, can provide valuable insights for possible therapeutic interventions. This review provides valuable insights into the molecular structure, chemistry, and molecular mechanisms associated with STEP61. This brain-specific phosphatase controls signaling molecules involved in neuronal activity and synaptic development. This review can aid researchers in gaining deep insights into the complex functions of STEP61.

Neuroprotective effect of Cubebin: A dibenzylbutyrolactone lignan on scopolamine-induced amnesia in mice.

BACKGROUND & OBJECTIVES: Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice. METHODS: Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain. RESULTS: Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC50value of 992 µM. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and oxidative stress level. INTERPRETATION & CONCLUSIONS: Cubebin showed promising protective activity in scopolamine-induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity.

Assessment of luteolin isolated from Eclipta alba leaves in animal models of epilepsy.

CONTEXT: Eclipta alba (Linn) Hassk. (Asteraceae) has been reported to be a nerve tonic and has been used to treat epilepsy in folk medicine. OBJECTIVE: The present study isolates and characterizes luteolin from E. alba and evaluates its antiepileptic potential in chemically induced acute and chronic models in mice. MATERIALS AND METHODS: The methanol extract (16.85% w/w) of E. alba leaves was subjected to fractionation for isolation of luteolin. In acute pentylenetetrazole (PTZ) model, luteolin (5, 10, 20 mg/kg, i.p.) was administered 30 min prior to PTZ injection (100 mg/kg) in Swiss albino mice. Kindling was induced by chronic administration of PTZ (35 mg/kg) on every alternate day (48 days). Luteolin was investigated on the course of kindling development and oxidative stress markers [reduced glutathione (GSH) and malondialdehyde (MDA)] in kindled mice. RESULTS: Single-dose pretreatment with luteolin (10 and 20 mg/kg, i.p.) was found to be effective in an acute PTZ model (100% protection from mortality) and it did not exhibit any effect on motor coordination at the same doses. PTZ-induced kindling was significantly (p < 0.001) prevented by luteolin (5, 10, 20 mg/kg, i.p.) in a dose-dependent manner. Luteolin restored levels of reduced GSH (p < 0.001) and decreased the level of MDA (p < 0.001), a marker of lipid peroxidation. DISCUSSION AND CONCLUSION: The results of the present study demonstrated that luteolin had an anticonvulsant effect in an acute PTZ model. Luteolin exhibited and inhibitory effect on the course of kindling and associated oxidative stress and hence could be a potential molecule in the treatment of epilepsy.

Identification of a novel class of quinoline-oxadiazole hybrids as anti-tuberculosis agents.

A series of novel quinoline-oxadiazole hybrid compounds was designed based on stepwise rational modification of the lead molecules reported previously, in order to enhance bioactivity and improve druglikeness. The hybrid compounds synthesized were screened for biological activity against Mycobacterium tuberculosis H37Rv and for cytotoxicity in HepG2 cell line. Several of the hits exhibited good to excellent anti-tuberculosis activity and selectivity, especially compounds 12m, 12o and 12p, showed minimum inhibitory concentration values<0.5µM and selectivity index>500. The results of this study open up a promising avenue that may lead to the discovery of a new class of anti-tuberculosis agents.

Polyethylene Sebacate-Silymarin Nanoparticles with Enhanced Hepatoprotective Activity.

The present study evaluates role of pullulan as hepatic targeting agent. Nanoparticles of silymarin (SIM) a hepatoprotective drug were prepared using polyethylene sebacate (PES) as biodegradable polymer and surface modified with pullulan. PES-SIM nanoparticles (PES-SIM NP) and PES-SIM nanoparticles surface modified with pullulan (PES-SIM-PUL) were prepared by nanoprecipitation. Nanoparticles were evaluated for hepatoprotective activity in a model of carbon-tetrachloride (CCl4) induced hepatotoxicity in rats. Pretreatment of rats with PES-SIM-NP and PES-SIM-PUL revealed reduced levels of SGOT, SGPT and ALKP compared to CCl4 treated group (p < 0.01) whereas levels of LPO and catalase were comparable to vehicle control suggesting enhanced hepatoprotection with nanoparticles. Histopathological evaluation of liver tissues also revealed better hepatoprotection with nanoparticles. Further significant decrease (p < 0.01) in levels of SGOT, SGPT and ALKP with difference PES-SIM-PUL than PES-SIM NP confirms the role of pullulan as hepatic targeting agent.

Non-invasive Biomarkers for Early Detection of Alzheimer's Disease: a New-Age Perspective.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the elderly population. It gradually leads to memory loss, loss of thinking ability, and an overall cognitive decline. However, exhaustive literature is available to suggest that pathological changes in the brain occur decades before the first clinical symptoms appear. This review provides insight into the non-invasive biomarkers for early detection of AD that have been successfully studied in populations across the globe. These biomarkers have been detected in the blood, saliva, breath, and urine samples. Retinal imaging techniques are also reported. In this study, PubMed and Google scholar were the databases employed using keywords "Alzheimer's disease," "neurodegeneration," "non-invasive biomarkers," "early diagnosis," "blood-based biomarkers," and "preclinical AD," among others. The evaluation of these biomarkers will provide early diagnosis of AD in the preclinical stages due to their positive correlation with brain pathology in AD. Early diagnosis with reliable and timely intervention can effectively manage this disease.

Correction: Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction.

Correction for 'Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction' by Swapnil S. Pawar et al., Dalton Trans., 2024, 53, 5770-5774, https://doi.org/10.1039/D3DT04296K.

Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction.

A novel cis-dioxomolybdenum(VI)-maltolate [MoO2(Mal)2] (1) is prepared as a stable molybdopterin model for the biomimetic catalysis of the oxidation of hypoxanthine in acetonitrile-water at room temperature. Compound 1 efficiently catalyzes the oxidation reaction of toluene, diphenylmethane, and styrene. Cyto- and oral-toxicity studies suggest its tremendous potential for application as a molybdenum supplement.

Mitochondriotropic Derivative of Ethyl Ferulate, a Dietary Phenylpropanoid, Exhibits Enhanced Cytotoxicity in Cancer Cells via Mitochondrial Superoxide-Mediated Activation of JNK and AKT Signalling.

Specific targeting of anti-cancer drugs to mitochondria is an emerging strategy to enhance cancer cell killing whilst simultaneously overcoming the problem of drug resistance, low bioavailability and limited clinical success of natural products. We have synthesized a mitochondria targeted derivative of Ethyl Ferulate (EF, a naturally occurring ester of ferulic acid), by conjugating it with triphenylphosphonium ion and compared its cytotoxicity with the parent molecule. Mito-Ethyl Ferulate (M-EF) was found to be more potent than EF (~ 400-fold) in inhibiting the growth of A549 and MCF-7 cells and suppressing the clonogenic potential of A549 cells. Notably, M-EF did not induce any cytotoxicity in normal cells (mouse normal fibroblast cells) up to a concentration of 25 µM. Furthermore, M-EF treatment induced significantly higher cell death in MCF-7 and A549 cells, as compared to EF via induction of apoptosis. M-EF treatment increased mitochondrial superoxide production and induced mitochondrial DNA damage and phosphorylation of JNK and AKT in A549 cells. Furthermore, M-EF induced increase in mitochondrial superoxide production and cytotoxicity was attenuated on pre-treatment with mitochondria-targeted antioxidant (mitoTEMPO) indicating the involvement of mitochondrial ROS in the cytotoxic effects of M-EF. Finally, in silico prediction revealed putative mitochondrial targets of M-EF which are known to regulate mitochondrial ROS and cell viability. In conclusion, the improved cytotoxic efficacy of M-EF exemplifies the use of mitochondria-specific drug delivery in future development of natural product based mitochondrial pharmacology.

Formulation, characterization, pharmacokinetics and antioxidant activity of phloretin oral granules.

Phloretin (PHL), a flavonoid of the dihydrogen chalcone class, is reported to have low oral bioavailability due to its poor solubility and absorption. A common approach to enhance the solubility of such flavonoids is solubilization in a polymeric or lipidic matrix which would help in enhance dissolution rate and solubility. Accordingly, in the current study PHL was dissolved in Gelucire® 44/14 by melt-fusion technique and the viscous semisolid melt was adsorbed on a solid carrier to obtain free flowing granules. SeDeM-SLA (Solid-Liquid Adsorption) expert system was employed to select the most suitable carrier. This study achieved positive outcomes through the successful development of formulated oral PHL granules. The granules exhibited good stability, and favourable pharmacokinetic properties. In addition, the selected carrier effectively retained the antioxidant properties of PHL.

Combinatorial cytotoxic effects of Curcuma longa and Zingiber officinale on the PC-3M prostate cancer cell line.

BACKGROUND: Many plant-derived products exhibit potent chemopreventive activity against animal tumor models as well as rodent and human cancer cell lines. They have low side effects and toxicity and presumably modulate the factors that are critical for cell proliferation, differentiation, senescence and apoptosis. The present study investigates the effects of some medicinal plant extracts from generally recognized as safe plants that may be useful in the prevention and treatment of cancer. METHODS: Clonogenic assays using logarithmically-growing cells were performed to test the effect. The cytotoxic effects of Curcuma longa and Zingiber officinale were studied using sulforhodamine B assay, tetrazolium dye assay, colony morphology and microscopic analysis. RESULTS: Out of the 13 lyophilized plant-derived extracts evaluated for growth-inhibitory effects on the PC-3M prostate cancer cell line, two extracts derived from C. longa and Z. officinale showed significant inhibitory effects on colony-forming ability. The individual and augmentative effects of these two extracts were tested for their narrow range effective lower concentration on PC-3M in clonogenic assays. At relatively lower concentrations, C. longa showed significant inhibition of colony formation in clonogenic assays; whereas at same concentrations Z. officinale showed only moderate inhibitory effects. However, when both the agents were tested together at the same concentrations, the combined effects were much more significant than their individual ones. On normal prostate epithelial cells both C. longa and Z. officinale had similar effects but at a lower magnitude. These observations were confirmed by several cytotoxicity assays involving the morphological appearance of the colonies, microscopic observations, per cent inhibition in comparison to control by sulforhodamine B and tetrazolium dye assay. CONCLUSIONS: From these observations, it was concluded that the combined effects of C. longa and Z. officinale are much greater than their individual effects, suggesting the role of multiple components and their synergistic mode of actions to elicit stronger beneficial effects.

An Update On Proficiency of Voltage-gated Ion Channel Blockers in the Treatment of Inflammation-associated Diseases.

Inflammation is the body's mechanism to trigger the immune system, thereby preventing bacteria and viruses from manifesting their toxic effect. Inflammation plays a vital role in regulating inflammatory mediator levels to initiate the wound healing process depending on the nature of the stimuli. This process occurs due to chemical release from white blood cells by elevating blood flow to the site of action, leading to redness and increased body temperature. Currently, there are numerous Non-steroidal anti-inflammatory drugs (NSAIDs) available, but these drugs are reported with adverse effects such as gastric bleeding, progressive kidney damage, and increased risk of heart attacks when prolonged use. For such instances, alternative options need to be adopted. The introduction of voltage-gated ion channel blockers can be a substantial alternative to mask the side effects of these currently available drugs. Chronic inflammatory disorders such as rheumatoid and osteoarthritis, cancer and migraine, etc., can cause dreadful pain, which is often debilitating for the patient. The underlying mechanism for both acute and chronic inflammation involves various complex receptors, different types of cells, receptors, and proteins. The working of voltage-gated sodium and calcium channels is closely linked to both inflammatory and neuropathic pain. Certain drugs such as carbamazepine and gabapentin, which are ion channel blockers, have greater pharmacotherapeutic activity for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states. This review intends to provide brief information on the mechanism of action, latest clinical trials, and applications of these blockers in treating inflammatory conditions.

Evaluation of Benzamide-Chalcone Derivatives as EGFR/CDK2 Inhibitor: Synthesis, In-Vitro Inhibition, and Molecular Modeling Studies.

BACKGROUND: EGFR (Epidermal Growth Factor Receptor) and CDK2 (Cyclin Dependent Kinase 2) are important targets in the treatment of many solid tumors and different ligands of these receptors share many common structural features. OBJECTIVE: The study involved the synthesis of benzamide-substituted chalcones and determination of their antiproliferative activity as well as a preliminary evaluation of EGFR and CDK2 inhibitory potential using both receptor binding and computational methods. METHODS: We synthesized 13 benzamide-substituted chalcone derivatives and tested their antiproliferative activity against MCF-7, HT-29 and U373MG cell lines using Sulforhodamine B Assay. Four compounds were examined for activity against EGFR and CDK2 kinase. The compounds were docked into both EGFR and CDK2 using Glide software. The stability of the interactions for the most active compound was evaluated by Molecular Dynamics Simulation using Desmond software. Molecular docking studies on mutant EGFR (T790M, T790M/L858R, and T790M/C797S) were also carried out. RESULTS: From the SRB assay, we concluded that compounds 1g, and 1k were effective in inhibiting the growth of the MCF-7 cell line whereas the other compounds were moderately active. Most compounds were either moderately active or inactive on U373 MG and HT-29 cell lines. Compounds 1g and 1k showed good inhibitory activity against CDK2 kinase while 1d and 1f were moderately active. Compounds 1d, 1f, 1g, and 1k were moderately active against EGFR kinase. Molecular docking reveals the involvement of one hydrogen bond with Met793 in binding with EGFR; however, it was not stable during the simulation and these compounds bind to the receptor mainly via hydrophobic contacts. This fact also points towards a different orientation of the inhibitor within the active site of EGFR kinase. Binding mode analysis for CDK2 inhibition studies indicates that hydrogen bonding interactions with Lys 33 and Leu83 are important for the activity. These interactions were found to be stable throughout the simulation. Considering the results for wild-type EGFR inhibition, the docking studies on mutants were performed and which indicate that the compounds bind to the mutant EGFR but the amino acid residues involved are similar to the wild-type EGFR, and therefore, the selectivity seems to be limited. CONCLUSION: These benzamide-substituted chalcone derivatives will be useful as lead molecules for the further development of newer inhibitors of EGFR and/or CDK2 kinases.

Ethyl ferulate, a lipophilic phenylpropanoid, prevents diabetes-associated renal injury in rats by amelioration of hyperglycemia-induced oxidative stress via activation of nuclear factor erythroid 2-related factor 2.

Diabetic nephropathy affects approximately 20%-40% of diabetes patients worldwide and is the leading cause of end-stage renal failure. Oxidative stress has been identified as a major causative factor in the development and progression of diabetic nephropathy; Nuclear factor erythroid 2-related factor 2 (Nrf2) activation protects the body against oxidative stress by induction of antioxidant enzymes. The renoprotective effect of ethyl ferulate was investigated in diabetes-induced renal injury. Ethyl ferulate was administered orally at three doses (50 mg/kg, 75 mg/kg, and 100 mg/kg). Metformin (500 mg/kg, p.o.) was used as a standard. Ethyl ferulate treatment decreased serum advanced glycation end products, glycosylated hemoglobin (HbA1c) levels, renal oxidative stress, tumor necrosis factor-α (TNF-α) level, and kidney hypertrophy index. It restored serum lipid profile, biomarkers of renal function, and mitigated histopathological signs of renal damage. Immunohistochemistry demonstrated higher Nrf2 protein levels in kidney sections of ethyl ferulate-treated rats. These findings suggest that ethyl ferulate ameliorated hyperglycemia-induced oxidative stress by increasing renal Nrf2 levels, thereby preventing diabetes-induced kidney injury. In conclusion, the present study endorses the usefulness of Nrf2 activators, such as ethyl ferulate, as adjuvant therapy for preventing the diabetic nephropathy. PRACTICAL APPLICATIONS: Ethyl ferulate (ethyl-3-hydroxyl-4-methoxycinnamate), a phenylpropanoid, is a naturally occurring ethyl ester of ferulic acid and is widely present in plants and especially grains, such as rice and maize. Our study has highlighted the renoprotective effect of ethyl ferulate in preventing diabetes-associated renal injury. The observed effect of ethyl ferulate is due to amelioration of diabetes-induced oxidative stress and inflammation, by activation of the Nrf2 pathway. These results indicate the potential of ethyl ferulate as a nutraceutical or adjuvant therapy in prevention of diabetic nephropathy.

Fabrication and characterization of starch-TPU based nanofibers for wound healing applications.

Wound dressings have undergone continuous and substantial evolution over time. Modern bandage materials constitute of electrospun biopolymers that enable rapid and effective wound healing due to the high surface area to volume ratio of the electrospun nanofibers and their porous structure. In the present study, nanofibrous bandages, containing a blend of starch-thermoplastic polyurethane (TPU), were developed by using the electrospinning technique. The electrospun nanofibrous mats were subsequently crosslinked with varying concentrations of glutaraldehyde in order to increase their water stability and mechanical properties. The nanofibrous bandages were characterized for their structural properties using SEM, FTIR, TGA, DSC, as well as for their water retention ability, water vapor transmission rate (WVTR), tensile strength and blood clotting efficiency. Cytotoxicity of the bandages was evaluated using human dermal fibroblast cells. Furthermore, the extent of wound healing enabled by the nanofibrous bandage was ascertained using Sprague-Dawley rats. The results revealed that the starch-TPU nanofibrous bandages facilitated enhanced wound-healing, as compared to the traditional dressing material, such as the cotton gauze.

Studies in molecular modeling, in-vitro CDK2 inhibition and antimetastatic activity of some synthetic flavones.

Naturally occurring flavonoids have been shown to possess anticancer activity. We have previously shown that certain synthetic flavonoids also exert significant antiproliferative potential in MOLT-4, MCF-7, and HepG2 cell lines. To this end, we evaluated eight synthetic flavones for their CDK2 binding by molecular docking. Most flavones showed interaction with Leu 83. Based on docking and antiproliferative activity, we chose 3'-nitroflavone and 3', 5'-dimethoxyflavone for the molecular dynamics (MD) simulation and CDK2 inhibition studies. MD simulation studies confirmed interactions with CDK2 (as observed in docking). Furthermore, the inhibitory activities of CDK2/cyclin A2 enzyme for 3'-nitroflavone and 3', 5'-dimethoxyflavone were found to be 6.17 and 7.19 �M, respectively. 3'-nitroflavone and 3', 5'-dimethoxyflavone displayed moderate activity in colony formation assay, wound-scratch assay, and Leighton tube studies. Based on these data, the synthesized flavones might have clinical potential as potential inhibitors of CDK2.

Mechanistic evaluation of Ursolic acid against rotenone induced Parkinson's disease- emphasizing the role of mitochondrial biogenesis.

Parkinson's disease (PD) is an age associated, progressive and a second most common neurodegenerative disease. It is caused due to degeneration of dopaminergic neurons in substantia nigra (SN). Various studies implicate mitochondrial dysfunction, oxidative stress, altered degradation of misfolded proteins in PD pathogenesis. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is reported to possess a number of biological activities viz. anti-oxidant, anti-inflammatory etc. The focus of our study was to assess the neuroprotective potential of UA against the rotenone induced pathophysiological alterations. In this study rats were subjected to stereotaxic bilateral injection of rotenone (12 µg/µl) in SN. Further, they were treated per-orally with UA (5 and 10 mg/kg) for 30 days. During the study, neurobehavioral tests comprising Rota-rod, Open field and Barnes maze (BMT) were conducted. At the end of 30 days, the antioxidant (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammatory (TNF-α) parameters, mitochondrial complex I, mitochondrial biogenesis (MB) and immunohistochemical analysis (TH positive neurons, Glial Fibrillary Acidic Protein (GFAP)) was performed. The results exhibited significant amelioration in the motor deficits by UA which can be attributed to the protection of TH positive neurons from degeneration. A significant improvement in the cognitive function due to UA was observed in BMT. Biochemically, the oxidative stress and inflammation triggered by rotenone was significantly diminished by UA. It also significantly obviated the complex I inhibition and promoted MB. The preliminary results thus firmly advocate the neuroprotective potential of UA to prevent rotenone induced neurotoxicity in rats.

Standardization of type 1 and type 2 diabetic nephropathy models in rats: Assessment and characterization of metabolic features and renal injury.

BACKGROUND: Diabetes mellitus and its complications, such as nephropathy, represent a global burden. Recent research focuses on developing drugs that specifically target the pathogenesis of diabetic nephropathy rather than merely treating hyperglycemia. Rodent models of animal disease are integral in drug discovery and represent an obligatory regulatory requirement. AIM: The aim of this study was to develop and standardize rat models of type 1 and type 2 diabetic nephropathy, resembling characteristics of human clinical condition. MATERIALS AND METHODS: Rats were administered streptozotocin (STZ) 50 mg/kg intraperitoneally (i.p.), and STZ 50 mg/kg i.p. + nicotinamide (NA) 110 mg/kg i.p., for induction of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), respectively. Metabolic parameters (body weight, feed and water intake, blood glucose, serum insulin, oral glucose tolerance test, intraperitoneal insulin tolerance test, and indices of insulin sensitivity) were evaluated to characterize the symptoms of T1DM and T2DM. Renal damage was confirmed by the estimation of renal function biomarkers, kidney antioxidant status, kidney hypertrophy index, and histopathology. RESULTS: STZ and STZ + NA administration increased blood glucose levels significantly. Metabolic parameters indicated that administration of STZ resulted in clinical features of human T1DM, whereas STZ + NA rats resembled human T2DM. STZ- and STZ + NA-treated rats developed diabetic nephropathy in 4 weeks, indicated by altered levels of renal function markers, increased kidney hypertrophy index, increased renal oxidative stress, and altered tissue architecture. The study proposes reproducible and cost-effective rat models for both T1DM- and T2DM-induced diabetic nephropathy characterized by stable metabolic features and typical renal lesions.

In Vivo Studies of 3D Starch-Gelatin Scaffolds for Full-Thickness Wound Healing.

In this study, we have combined the wound-healing properties of two biodegradable polymers, viz., starch and gelatin, and have reinforced their mechanical strength through cross-linking. Further, scaffolds of this polymer combination were used to support an organotypic culture of human skin for wound healing. Human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) were isolated and were seeded on the scaffolds on days 1 and 7, respectively. The scaffold was then air-lifted to develop a stratified epidermal layer. Hematoxylin and eosin (H&E) staining and immunohistochemical analysis ascertained that the histology of the skin organotypic culture was similar to that of the human skin. For in vivo animal investigations, the scaffolds were transplanted in a full-thickness wound mouse model, as a one-step procedure, wherein the artificial skin substitute showed the presence of well-defined epidermis and formation of stratum basale by day 14. By combining the inherent properties of both the materials, we have synthesized a cost-effective porous scaffold with good mechanical strength and excellent biocompatibility that can be easily adapted for commercial use. The aforementioned scaffold may integrate with the surrounding tissue, accelerate wound closure, and promote tissue reorganization and remodeling.