Exploring the potential therapeutic benefits of 7-methoxy coumarin for neuropathy pain: an in vivo, in vitro, and in silico approach.

BACK GROUND: 7-Methoxycoumarin (7-MC) is well recognized for its anti-inflammatory and anti-nociceptive actions. Its capacity to lessen neuropathic pain hasn't been documented yet. Hence the impact of 7-MC on vincristine-induced peripheral neuropathic pain in rodents was investigated. The investigation also looked at the impact of 7-MC in reducing neuropathic pain via voltage-gated calcium channels and phospholipase enzyme inhibition using pertinent in vitro and in silico methods. METHODS AND RESULTS: Vincristine (0.1 mg/kg, i.p., daily) was administered continuously for 7 days to induce peripheral neuropathic pain in mice, with cold allodynia and thermal hyperalgesia and evaluated on the 8th day using the acetone bubble test and hot water tail immersion test. In order to derive the mechanistic approach for ameliorating neuropathic pain, the role of 7-MC in the inhibition of the phospholipase enzyme, gene expression studies on voltage-gated calcium channels using mouse BV2 microglial cells and in silico studies for its calcium channel binding affinity were also performed. The test compounds reduced vincristine-induced cold allodynia and thermal hyperalgesia in mice in a dose-dependent experiments. In vitro studies on phospholipase inhibition by 7-MC showed an IC50 of 27.08 µg/ml and down-regulated the gene expression of calcium channels in the BV2 microglial cell line. In silico docking scores for 7-MCwere higher than the standard drug gabapentin. CONCLUSION: The compound 7-MC has shown promise in alleviating vincristine-induced peripheral neuropathicin mice. Studies conducted in parallel, both in silico and in vitro have demonstrated that 7-MC effectively reduces neuropathic pain. This pain reduction is achieved through two mechanisms: inhibiting the phospholipase enzyme and blocking voltage-gated calcium channels.

Potential molecular mechanisms of myrtenal against colon cancer: A systematic review.

Colon cancer is a serious health problem across the globe with various dietary lifestyle modifications. It arises as an inflammation mediated crypts in the colon epithelial cells and undergoes uncontrolled cell division and proliferation. Bacterial enzymes contribute to a major outbreak in colon cancer development upon the release of toxic metabolites from the gut microflora. Pathogen associated molecular patterns and damage associated molecular patterns triggers the NLPR3 inflammasome pathways that releases pro-inflammatory cytokines to induce cancer of the colon. Contributing to this, specific chemokines and receptor complexes attribute to cellular proliferation and metastasis. Bacterial enzymes synergistically attack the colon mucosa and degenerate the cellular integrity causing lysosomal discharge. These factors further instigate the Tol like receptors (TLRs) and Nod like receptors (NLRs) to promote angiogenesis and supply nutrients for the cancer cells. Myrtenal, a monoterpene, is gaining more importance in recent times and it is being widely utilized against many diseases such as cancers, neurodegenerative diseases and diabetes. Based on the research data's, the reviews focus on the anticancer property of myrtenal by emphasizing its therapeutic properties which downregulate the inflammasome pathways and other signalling pathways. Combination therapy is gaining more importance as they can target every variant in the cellular stress condition. Clinical studies with compounds like myrtenal of the monoterpenes family is provided with positive results which might open an effective anticancer drug therapy. This review highlights myrtenal and its biological potency as a cost effective drug for prevention and treatment of colon cancer.

Modulation of PPAR-γ, SREBP-1c and inflammatory mediators by luteolin ameliorates ß-cell dysfunction and renal damage in a rat model of type-2 diabetes mellitus.

BACKGROUND: Natural products have been recommended as a complementary therapy for type 2 diabetes mellitus (T2DM) due to constraints of safety and tolerability of existing anti-diabetic agents. Luteolin exhibits anti-diabetic and anti-inflammatory effects. Hence, the impact of luteolin on glucose homoeostasis and organ damage was investigated in high-fat diet (HFD) and streptozotocin (STZ) induced T2DM in rats. METHODS AND RESULTS: Male Wistar rats were maintained on HFD (provided 55% energy as fat) for 10 days. Subsequently, a single dose of 40 mg/kg STZ was injected intraperitoneally on the 11th day. Seventy-two hours after STZ administration, diabetic rats with established hyperglycemia (fasting serum glucose > 200 mg/dL) were randomized into different groups having six rats each and orally administered either 0.5% hydroxy propyl cellulose or pioglitazone (10 mg/kg) or luteolin (50 mg/kg or 100 mg/kg) once daily for 28 days, while continuing HFD for respective groups. Luteolin significantly reduced hyperglycaemia, homoeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) levels, and improved hypoinsulinemia and HOMA of b-cell function (HOMA-B) in a dose-dependent manner. Increased TNF-α, IL-6 and NFκB levels in diabetic rats were significantly regulated. Additionally, luteolin significantly augmented PPAR-γ expression while attenuating sterol regulatory element binding protein-1c (SREBP-1c) expression. Histopathological scrutiny validated that luteolin effectively attenuated HFD-STZ-induced injury in pancreatic ß-cells and kidneys to near normalcy. CONCLUSION: Our study showed that luteolin ameliorated hyperglycemia and improved hypoinsulinemia, ß-cell dysfunction, and renal impairment in HFD-STZ-induced diabetic rats by attenuating inflammation and dysregulated cytokine secretion through modulation of PPAR-γ, TNF-α, IL-6 and NF-kB expression and down-regulation of SREBP-1c.

Autoinjector - A smart device for emergency cum personal therapy.

Autoinjectors are self-injectable devices; they are important class of medical devices which can deliver drugs through subcutaneous or intramuscular route. They enclose prefilled syringes or cartridges which are driven by a spring system. The major benefits of this device are easy self-administration, improved patient compliance, reduced anxiety, and dosage accuracy. Immediate treatment during emergency conditions such as anaphylaxis, migraine, and status epilepticus or for chronic conditions like psoriasis, diabetes, multiple sclerosis, and rheumatoid arthritis, Reformulation of first-generation biologics, technical advancements, innovative designs, patient compliance, overwhelming interest for self-administration all these made entry of more and more autoinjectors into use. In this review, intensive efforts have been made for exploring the different types of currently available autoinjectors for the management of emergency and chronic diseases.

Evaluation and In Vitro Study of an Electrospun Bone Tissue Membrane for Bone Regeneration: A Novel Perspective.

Objectives In the present study, electrospun bone tissue membrane (EBTM) was prepared using polyvinylidene fluoride (PVDF), gelatin (gel), and demineralized bone matrix (DBM) by electrospinning method for its potential application in bone tissue regeneration. Materials and methods The prepared EBTM was evaluated using high-resolution scanning electron microscopy (HR-SEM), energy-dispersive X-ray spectroscopy (EDX; Silicon Drift 2017, USA), thermogravimetric analysis (TGA), and mechanical properties such as tensile strength (MPa), elongation at break (%), flexibility (%), and water absorption (%). In vitro bioactivity testing of EBTM using simulated body fluid (SBF) was performed after 14 days of immersion. Cell viability was tested using human osteoblast-like cells (MG-63) to prove biocompatibility. Results EBTM had superior surface morphology, thermal stability, and mechanical strength. The mechanical properties of EBTM were promising, enabling its use in tissue engineering. Bioactivity test showed that the EBTM surface developed calcium (Ca) and phosphate (P) after 14 days of being immersed in SBF. Additionally, a biocompatibility investigation revealed that EBTM was covered with more viable cells. Conclusion EBTM with sufficient mechanical strength, thermal stability, surface morphology, Ca deposition, and biocompatibility could serve as a plausible material for bone tissue engineering (skin, ligament, cartilage, and bone).

Recent advancements in small interfering RNA based therapeutic approach on breast cancer.

Breast cancer (BC) is the most common and malignant tumor diagnosed in women, with 2.9 million cases in 2023 and the fifth highest cancer-causing mortality worldwide. Recent developments in targeted therapy options for BC have demonstrated the promising potential of small interfering RNA (siRNA)-based cancer therapeutic approaches. As BC continues to be a global burden, siRNA therapy emerges as a potential treatment strategy to regulate disease-related genes in other types of cancers, including BC. siRNAs are tiny RNA molecules that, by preventing their expression, can specifically silence genes linked to the development of cancer. In order to increase the stability and effectiveness of siRNA delivery to BC cells, minimize off-target effects, and improve treatment efficacy, advanced delivery technologies such as lipid nanoparticles and nanocarriers have been created. Additionally, combination therapies, such as siRNAs that target multiple pathways are used in conjunction with conventional chemotherapy agents, have shown synergistic effects in various preclinical studies, opening up new treatment options for breast cancer that are personalized and precision medicine-oriented. Targeting important genes linked to BC growth, metastasis, and chemo-resistance has been reported in BC research using siRNA-based therapies. This study reviews recent reports on therapeutic approaches to siRNA for advanced treatment of BC. Furthermore, this review evaluates the role and mechanisms of siRNA in BC and demonstrates the potential of exploiting siRNA as a novel target for BC therapy.

Hydroxycitric acid and capsaicin combination alleviates obesity-induced testicular apoptosis, oxidative stress and inflammation.

Recent research in rodents suggests that oxidative stress, inflammation, and apoptosis in the testes caused by high-fat diets (HFD) are a cause of male infertility. To investigate the therapeutic efficacy of the combination of hydroxycitric acid and capsaicin (HCC) against male reproductive disorders, we developed an HFD-induced obese rat model. Rats received HFD supplementation for 21 weeks, which induced obesity. From week 16, HCC (100 mg/kg body weight) was administered to investigate its potential to treat testicular toxicity. According to the results of the current study, treatment of obese rats with HCC improved their sperm quality, increased the production of testosterone, follicle-stimulating hormone, and luteinizing hormone and significantly increased the activities of steroidogenic enzymes and corresponding mRNA levels. In addition, HCC decreased lipid peroxidation and nitric oxide levels in both spermatozoa and testes while increasing the expression of mRNA for the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in the testes, which in turn reduced oxidative stress in the testes. Moreover, after HCC treatment, testicular tissues showed a remarkable decrease in mRNA levels responsible for inflammation (TNF-α, IL-6, NF-κB) and apoptosis (Bax and Bcl-2). Our results suggest that HCC may alleviate obesity-induced male reproductive dysfunction by attenuating oxidative stress, inflammation, and apoptosis in the testes of HFD-induced obese male rats.

Luteolin Mitigates Diabetic Dyslipidemia in Rats by Modulating ACAT-2, PPARα, SREBP-2 Proteins, and Oxidative Stress.

Diabetic dyslipidemia is a crucial link between type-2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular diseases (ASCVD). Natural biologically active substances have been advocated as complementary remedies for ASCVD and T2DM. Luteolin, a flavonoid, exhibits antioxidant, hypolipidemic, and antiatherogenic effects. Hence, we aimed to determine influence of luteolin on lipid homeostasis and hepatic damage in rats with T2DM induced by high-fat-diet (HFD) and streptozotocin (STZ). After being fed HFD for 10 days, male Wistar rats received 40 mg/kg STZ intraperitoneal injection on 11th day. Seventy-two hours later, hyperglycemic rats (fasting glucose > 200 mg/dL) were randomized into groups, and oral hydroxy-propyl-cellulose, atorvastatin (5 mg/kg), or luteolin (50 mg/kg or 100 mg/kg) administered daily, while continuing HFD for 28 days. Luteolin significantly ameliorated dyslipidemia levels and concomitantly improved atherogenic index of plasma in a dose-dependent manner. Increased levels of malondialdehyde and diminished levels of superoxide dismutase, catalase, and glutathione in HFD-STZ-diabetic rats were significantly regulated by luteolin. Luteolin significantly intensified PPARα expression while decreasing expression of acyl-coenzyme A:cholesterol acyltransferase-2 (ACAT-2) and sterol regulatory element binding protein-2 (SREBP-2) proteins. Moreover, luteolin effectively alleviated hepatic impairment in HFD-STZ-diabetic rats to near-normal control levels. The findings of the present study expound mechanisms by which luteolin mitigated diabetic dyslipidemia and alleviated hepatic impairment in HFD-STZ-diabetic rats by amelioration of oxidative stress, modulation of PPARα expression, and downregulation of ACAT-2 and SREBP-2. In conclusion, our results imply that luteolin may be efficacious in management of dyslipidemia in T2DM, and future research may be essential to substantiate our findings.

Emerging Role of RNA m5C Modification in Cardiovascular Diseases.

Epitranscriptomics is the emerging field of research that comprises the study of epigenetics changes in RNAs. Progressing development in the field of epigenetics has helped to manage and comprehend human diseases. RNA methylation regulates all aspects of RNA functions, which are involved in the pathogenesis of human diseases. Interestingly, RNA m5C methylation is significantly linked to various types of human disease, including cardiovascular diseases (CVD). The m5C methylation is controlled by m5C regulatory proteins, which act as methyltransferase, demethyltransferase, and RNA-binding protein. Dysregulated expression in m5C regulatory proteins is significantly associated with cardiovascular disease, and these regulatory proteins have crucial roles in biological and cellular functions. This review is mainly focused on the role of RNA m5C modification in CVD and mitochondrial dysfunction. Thus, m5C will contribute to discovering the new diagnostic marker and therapeutic target for CVD.

Anticancer Property of Digera muricata Leaf Extract: An In Vitro Study.

Aim The aim was to evaluate the anticancer potential of Digera muricata ethanolicleaf extract on MG-63 osteosarcoma cell lines. Materials and methods The anti-cancer properties of Digera muricata ethanolic leaf extract were evaluated on osteosarcoma cell lines using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the morphological changes in MG-63 cells were assessed after 24 hours using microscopic observation. Additionally, fluorescence microscopy was employed to evaluate the apoptotic changes after acridine orange/ethidium bromide (AO/EtBr) dual staining. Results The MTT assay revealed a dose-dependent cell death. The cell viability decreased with increase in concentrations of the extract, The cell viability was 89.98 ± 4.89 percentage at 25 µg/ml and 15.64 ± 3.64 percentage at 200 µg/ml concentrations. A concentartion of 116.95 µg/ml showed 50% inhibition (IC50). The morphological and dual staining studies also showed the extract's effectiveness in inducing apoptosis. Conclusion The ethanolic leaf extract of D. muricata could impart good antiproliferative activity in MG-63 cell lines. The extract could also induce apoptosis and hence, it may be considered as a potential anticancer agent for the development of drug formulation for the treatment of osteosarcoma.

Beta-glucan suppresses high-fat-diet-induced obesity by attenuating dyslipidemia and modulating obesogenic marker expressions in rats.

The current study was designed to evaluate the therapeutic potential of beta-glucan (BG), which is a key bioactive compound predominantly present in mushrooms and cereals against high-fat-diet (HFD)-induced obesity, and to understand its mechanism of action. Obesity was induced in rats by supplementing the diet with HFD and BG (40 mg/kg body weight) for a period of 6 weeks. At the end of the experimental period, the body weight, as well as hyperglycemic, dyslipidemia, and obesogenic marker expressions, was assessed in the control group and in the experimental obese rats. Administration of BG to obese rats significantly reduced body weight gain and attenuated hyperglycemia, which was confirmed by the decreased blood glucose and insulin resistance. At the same time, BG mitigated dyslipidemia by altering expressions of peroxisome proliferator-activated receptor-gamma (PPAR-γ), sterol regulatory element-binding protein 1 (SREBP-1c), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, and fatty acid-binding protein-4 (Fab-4) in HFD-induced obese rats. In conclusion, this study revealed that BG is a potential candidate to ameliorate HFD-induced obesity by modulating obesogenic marker expressions, especially by regulating the master regulator PPAR-γ.

Exosome Mediated Cancer Therapeutic Approach:Present Status and Future Prospectives.

The unique extracellular vesicles (EVs) or exosomes formed by the sequential invagination of the plasma membrane are diverse and encompass important constituents with biological functions. Speculations on its cell independent biological functions are significant and pose them as vital biomarkers and as drug delivery vehicles especially in cancer. EVs possess theragnostic values and are known to elicit specific immune response. Exosomes can also serve as potential nanocarriers for delivering miRNA, siRNA, anti-cancer drugs and membrane-associated proteins. Exosomes play a crucial role in regulating tumour progression, metastasis, and angiogenesis. This review thus portrays the multiple facets of exosomes, in concert with the source for exosomes production and further on its regulation and intercellular communication. The review also explores the recent advances, present status and the future prospective in the application of exosomes in cancer therapeutics and cancer diagnostics.

Recent trends in macromolecule-conjugated hybrid quantum dots for cancer theranostic applications.

Quantum dots (QDs) are small nanoparticles with semiconductor properties ranging from 2 to 10 nanometers comprising 10-50 atoms. The single wavelength excitation character of QDs makes it more significant, as it can excite multiple particles in a confined surface simultaneously by narrow emission. QDs are more photostable than traditional organic dyes; however, when injected into tissues, whole animals, or ionic solutions, there is a significant loss of fluorescence. HQD-based probes conjugated with cancer-specific ligands, antibodies, or peptides are used in clinical diagnosis. It is more precise and reliable than standard immunohistochemistry (IHC) at minimal protein expression levels. Advanced clinical studies use photodynamic therapy (PDT) with fluorescence imaging to effectively identify and treat cancer. Recent studies revealed that a combination of unique characteristics of QDs, including their fluorescence capacity and abnormal expression of miRNA in cancer cells, were used for the detection and monitoring progression of cancer. In this review, we have highlighted the unique properties of QDs and the theranostic behavior of various macromolecule-conjugated HQDs leading to cancer treatment.

Re-appraising the role of flavonols, flavones and flavonones on osteoblasts and osteoclasts- A review on its molecular mode of action.

Bone disorders have become a global concern illustrated with decreased bone mineral density and disruption in microarchitecture of natural bone tissue organization. Natural compounds that promote bone health by augmenting osteoblast functions and suppressing osteoclast functions has gained much attention and offer greater therapeutic value compared to conventional therapies. Amongst several plant-based molecules, flavonoids act as a major combatant in promoting bone health through their multi-faceted biological activities such as antioxidant, anti-inflammatory, and osteogenic properties. They protect bone loss by regulating the signalling cascades involved in osteoblast and osteoclast functions. Flavonoids augment osteoblastogenesis and inhibits osteoclastogenesis through their modulation of various signalling pathways. This review discusses the role of various flavonoids and their molecular mechanisms involved in maintaining bone health by regulating osteoblast and osteoclast functions.

Antibacterial potential of inulinase enzyme obtained from Nocardiopsis sp.

The enriched nutritional and functional properties of inulinase with wide attention are considered commercial/industrial food enzymes. It can be produced by many microorganisms such as yeasts, fungi, and bacteria. Nocardiopsis is a genus under Actinomycetes, which has biotechnologically important microorganisms. This study aims to isolate and identify marine Actinomycetes Nocardiopsis species and to evaluate the antibacterial potential of the inulinase enzyme obtained from it. Marine actinobacteria (Nocardiopsis sp.) were isolated from sediment samples on YM agar. The isolate was identified by biochemical analysis of cell walls (amino acid and sugar). Enzyme screening assay was performed with temperature and pH influence in the production inulinase enzyme production. Antibacterial activity and minimal inhibitory activity of inulinase enzyme were performed with Staphylococcus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Antimicrobial testing revealed that with higher concentrations of inulinase enzyme, the zone of inhibition of bacterial growth increased, and the minimum inhibitory concentration of inulinase enzyme that prevented the growth of bacteria was close to the standard tetracycline. Inulinase enzyme obtained from Nocardiopsis species shows good antibacterial activity against Staphylococcus aureus, K. pneumoniae, and P. aeruginosa in comparison to the standard, tetracycline.

Amylase-producing marine actinobacterium of Micromonospora sp. and their potential antibacterial effects against oral pathogens.

Marine actinobacteriological investigation is still in its beginning in India. Earlier, in the 20th century, studies on Actinobacteria were started and highly concentrated on diversity, identification, and screening for enzymes, antibiotics, and enzyme inhibitors. With the spurge of infectious diseases requiring antibiotics, novel antibiotics are in search as the prevalent ones have declined uses, due to the antibiotic-resistant microbial growth. Unexploited ecosystems are studied for isolation of rare species such as Actinobacteria which are expected to yield newer metabolites. The marine actinobacterial isolation and enumeration were done from sediment samples. The marine Actinobacteria were identified by conventional methods. Further amylase enzyme production and their antibacterial activities are also done following the standard methods. The Micromonospora sp. was identified by chemotaxonomical characteristics and spore chain morphology. Further, the amylase enzyme production was done and quantification of enzyme also done. The potential antimicrobial activity from the amylase enzyme was done. Zone of inhibition and minimal inhibitory concentration were calculated. It concluded that potent antibacterial activity was obtained from Actinobacteria Micromonospora sp. producing amylase enzymes.

Extracellular polymeric substances from marine actinobacterium of Micromonospora sp. and their antioxidant activity.

Actinobacteria, Gram-positive bacteria are the largest phyla among the major species in the bacteria domain. Micromonospora sp. is one of the secondary metabolite-producing Actinobacteria, and it has a comprehensive spectrum of antibacterial, antifungal, antitumor, antiviral, antiparasitic, diabetogenic anti-inflammatory, insecticidal, inhibitory of enzyme, antioxidant, and other biological activities. The objective of the study is to assess the antioxidant activity of the Actinobacterium Micromonospora sp. producing extracellular polymeric substances (EPSs). Enumeration and isolation of Actinobacteria from sediment samples are done. The marine Actinobacteria, Micromonospora sp. are identified by melanoid pigments and other chemotaxonomical characteristics. EPS is produced from the potential marine Actinobacteria and their components are estimated. The total antioxidant value is found for the EPS. The antioxidant activity of the ascorbic acid equivalent which was 142.65 µg/ml was equivalent to 150 µg/ml of the total antioxidant activity of the EPS produced. The role of different antioxidants and the action in different diseases were challenged since they could act as many mechanisms such as reducing power, providing hydrogen to radicals, and scavenging activity (free radical). To conclude, the potent antioxidant activity was obtained from Actinobacteria Micromonospora sp. producing extracellular substances. These extracts might bear anticancer metabolites and are considered a potent anticancer drug.

Biomedical Application of Chitosan and Piper Longum-assisted Nano Zinc Oxide-based Dental Varnish.

The aim of this study was to prepare zinc oxide nanoparticles from chitosan and Piper longum and to assess the antimicrobial activity. The chitosan is a biocompatible polymer and also used as a polymeric nanoparticle. P. longum is a flowering vine which is commonly used as a spice to season food. It is also being used as a traditional medicine that treats asthma, viral hepatitis, cough, and respiratory infections. Dental varnishes are usually applied on the tooth surface and are similar to fluoride varnishes that prevent tooth decay. The zinc oxide nanoparticles were prepared using the P. longum plant extract and color change was noted. The nanoparticle formation was confirmed using UV-Vis spectroscopy and the solution was centrifuged for 10 min and the nanoparticles were collected. The chitosan was prepared using 1% acetic acid with chemical reaction. In a centrifuge tube, 100 µL of prepared nanoparticles, with the addition of chemical ingredients the varnish, were prepared. The study showed Staphylococcus aureus to be very sensitive with a maximum zone of inhibition followed by Sterptococcus mutants, Enterococcus faecalis, and Candida albicans. P. longum- and chitosan-assisted nano zinc oxide-based dental varnishes will be a better choice for infections caused by S. aureus and S. mutans.

p-Coumaric Acid Nanoparticles Ameliorate Diabetic Nephropathy via Regulating mRNA Expression of KIM-1 and GLUT-2 in Streptozotocin-Induced Diabetic Rats.

Diabetic nephropathy (DN) has become a leading cause of end-stage renal failure worldwide. The goal of the current study was to examine the protective effects of chitosan-loaded p-Coumaric acid nanoparticles (PCNPs) in nephrotoxicity induced by streptozotocin (STZ). Because of the antidiabetic, anti-inflammatory, and antioxidant properties of PCNPs, the development of DN may be considerably decreased. In this study, the rats received a single intraperitoneal injection (i.p.) of STZ (45 mg/kg) to induce DN. PCNPs were given orally 80 mg/kg b.w to the rats for a duration of four weeks. Body weight, kidney weight, blood glucose, and insulin levels were measured at the end of the experiment. Serum and urine parameters were also examined, along with the histological, immunobiological, and tumor necrosis factor (TNF) and interleukin-6 (IL-6) expression of the nephrotic rats. To comprehend the impact of PCNPs, the expression patterns of the kidney injury molecule (KIM-1) and glucose transporter-2 (GLUT-2) were evaluated. Administration of PCNPs significantly increased body weight, decreased kidney weight and also ameliorated blood glucose levels in the nephropathic rats. The administration of PCNPs also reverted the levels of urea, serum creatinine, urinary NAG, ß-glucuronidase and albumin to near-normal levels. The administration of PCNPs also caused the levels of serum and urine parameters to return to near-normal levels. Additionally, the PCNP-treated rats had markedly reduced TNF-α, IL-6, and KIM-1 expressions as well as enhanced GLUT-2 mRNA expression. Our findings clearly showed that PCNP administration prevents the onset of DN in rats by lowering hyperglycemia, decreasing inflammation, and improving the expression of GLUT-2 mRNA in nephropathic rats.

Safety evaluation of antibacterial and analgesic autoinjector devices for rapid administration during emergency situations: a crossover study in rabbits.

Objective: The objective of the present study was to evaluate the safety and tolerability of autoinjector devices (AIDs) in rabbits by intramuscular (i.m.) administration, using haematological and biochemical markers. Introduction: Emergency and mass casualty situations require immediate drug delivery for which AIDs are preferred. The tolerability of amikacin as antibacterial and buprenorphine as analgesic AID has been studied in rats by intraperitoneal administration. In the present study, it was evaluated in rabbits by i.m. administration. Methods: Water-filled glass cartridges (2.3-2.4 mL) were converted to amikacin (106 mg/mL) and buprenorphine (0.128 mg/mL) cartridges. Dual dose AID was used for i.m. administration (1.2 mL). The study was done as a crossover design on 12 rabbits. Initially, three rabbits each were given manually or AID, 57 mg/kg amikacin, and three rabbits each by manual or by AID, 0.07 mg/kg buprenorphine for 7 days. After 1 month, the injections were changed in the rabbits. In the place of manual injection, AID and in the place of amikacin, buprenorphine injection was given. This ensured that all rabbits received 14 injections, 7 manual and 7 AID consisting of 7 amikacin and 7 buprenorphine. 24 h before and 24 h after last drug administrations, blood was withdrawn from ear vein for haematological and biochemical estimations. Results: The rabbits were healthy, active and no sign of any injection-related changes were observed after administration of amikacin and buprenorphine by manually or by AID. The haematological and biochemical parameters showed similar changes in manual and AID administration of amikacin and buprenorphine. Conclusion: The present study of amikacin and buprenorphine by AID shows the safety of the device and is recommended for further experimentation. These AIDs are intended for self-administration during emergency and mass causality situation and are suitable for adults and children, as well as farm and pet animals.