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Amomum dealbatum Roxb. parts have been traditionally used as remedies for joint pain, diabetes, muscular rheumatism, antiseptic, and abscesses in Arunachal Pradesh, Assam, and Tripura. Ethyl acetate sub-fraction E3 had significantly inhibited the α-glucosidase (IC50 5.385 μg/mL). The molecular docking revealed quercetin-3-O-galactoside to be the most potent α-glucosidase inhibitor (binding energy −43.214 kcal/mol). Using the QSAR model, the pIC50 values of myricetin, gallic acid, quercetin-3-O-galactoside, and acarbose were predicted to be 5.65235, 4.39858, 5.65235, and 6.03058, respectively. For the first time, quercetin-3-O-galactoside, myricetin, and gallic acid have been isolated from the flowers of A. dealbatum (ADF). E3 decreased blood glucose level to a near-normal concentration (100.60 ± 2.94 mg/dL) in comparison to diabetic control rats (575.20 ± 24.80 mg/dL). The results have strongly suggested the potential of ADF in treating diabetes. This lesser-known plant has the potential to uncover its full medicinal properties through further in-depth research. [ABSTRACT FROM AUTHOR]

Determining the safety of a newly developed experimental product is a crucial condition for its medical use, especially for clinical trials. In this regard, four hydrogel-type formulations were manufactured, all of which were based on carbomer (Blank-CP940) and encapsulated with caffeine (CAF-CP940), phosphorus derivatives (phenyl phosphinic (CAF-S1-CP940) and 2-carboxyethyl phenyl phosphinic acids (CAF-S2-CP940)). The main aim of this research was to provide a comprehensive outline of the biosafety profile of the above-mentioned hydrogels. The complex in vitro screening (cell viability, cytotoxicity, morphological changes in response to exposure, and changes in nuclei morphology) on two types of healthy skin cell lines (HaCaT—human keratinocytes and JB6 Cl 41-5a—murine epidermal cells) exhibited a good biosafety profile when both cell lines were treated for 24 h with 150 μg/mL of each hydrogel. A comprehensive analysis of the hydrogel's impact on the genetic profile of HaCaT cells sustains the in vitro experiments. The biosafety profile was completed with the in vivo and in ovo assays. The outcome revealed that the developed hydrogels exerted good biocompatibility after topical application on BALB/c nude mice's skin. It also revealed a lack of toxicity after exposure to the hen's chicken embryo. Further investigations are needed, regarding the in vitro and in vivo therapeutic efficacy and safety for long-term use and potential clinical translatability. [ABSTRACT FROM AUTHOR]

Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p<0.05) attenuated the memory deficit, anxiety, and depressive-like behavior. Moreover, histopathological, hematological, serological, and endogenous antioxidant profiles indicated substantial AIP of ACs. Findings of comet assay further bolstered the compelling evidence as DNA damage was significantly (p<0.05) curbed down after ACs (100 mg/kg) treatment. All these outcomes implied that ACs exhibited AIP in a dose-dependent manner with maximal AIP imparted by artemisinin (100 mg/kg). This pre-clinical investigation avers the tremendous AIP of ACs targeting key molecular pathways. The current study divulges artemisinin as the most potent antiinflammatory agent among the tested compounds. [ABSTRACT FROM AUTHOR]

2-Phenoxyethanol (PhE) is an aromatic glycol ether and is used in a variety of functions and applications, e.g., as preservative in pharmaceuticals, cosmetic and personal care products, as biocide in disinfectants (e.g. human hygiene), or as a solvent in formulations (e.g. coatings, functional fluids). Despite its widespread use, little is yet known on its biotransformation and toxicokinetics in humans. Therefore, a pilot study was conducted with oral administration of PhE (5 mg/kg body weight) to five volunteers. Blood and urine samples were collected and analyzed for PhE and three of its presumed metabolites up to 48 h post-exposure. Additionally, one volunteer was dermally exposed to PhE and monitored until 72 h post-exposure. PhE was rapidly resorbed following both oral and dermal application with tmax-levels in blood of about 1 h and 3 h, respectively. Metabolism of PhE was observed to be rather extensive with phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) as the main metabolites found in blood and urine following oral and dermal exposure. PhE was excreted rapidly and efficiently via urine mostly in metabolized form: following oral exposure, on average 77% and 12% of the applied dose was excreted within 48 h as PhAA and 4-OH-PhAA, respectively. A similar metabolism pattern was observed following the single dermal exposure experiment. The obtained data on biotransformation and toxicokinetics of PhE in humans provide valuable information on this important chemical and will be highly useful for pharmacokinetic modelling and evaluation of human PhE exposure. [ABSTRACT FROM AUTHOR]

While personalized cancer therapies have improved treatment efficacy for specific cancer types, cancers with unclear genetic factors remain a challenge. Gold nanorods (GNRs) have gained attention as cancer therapies due to their anticancer effects even without light irradiation. This study investigates the anticancer effects of citrate-stabilized gold nanorods (CGNRs) on melanoma cell lines and tumors, as well as the factors influencing their efficacy. The study found that CGNRs exhibited strong sensitivity in specific cancer cells but not in normal cells. Cell viability analysis showed that CGNRs induce cell death in a concentration-dependent manner, and their anticancer effects are mainly due to necrosis. In vivo experiments using a murine melanoma model showed that intratumoral administration of CGNRs significantly suppressed tumor growth without body weight loss. Interestingly, our results suggest that the anticancer effects of CGNRs were independent of their cellular uptake efficiency but may be highly correlated with the aggressiveness of cancer cells. Overall, the results suggest that CGNRs have promising potential as a specific treatment for melanoma, especially for aggressively proliferating cells, and may represent an alternative or complementary therapy to conventional chemotherapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of local administration of melatonin (MLT) on molecular biomarkers and calvaria bone critical defects in female rats with or without osteoporosis, associated or not with a xenogeneic biomaterial. Forty-eight female rats were randomly divided into two groups: (O) ovariectomized and (S) placebo groups. After 45 days of osteoporosis induction, two critical-size defects (5 mm diameter) were created on the calvaria. The groups were subdivided according to the following treatment: (C) Clot, MLT, MLT associated with Bio-Oss® (MLTBO), and Bio-Oss® (BO). After 45 days, the defect samples were collected and processed for microtomography, histomorphometry, and biomolecular analysis (Col-I, BMP-2, and OPN). All animals had one femur harvested to confirm the osteoporosis. Microtomography analysis demonstrated a bone mineral density reduction in the O group. Regarding bone healing, the S group presented greater filling of the defects than the O group; however, in the O group, the defects treated with MLT showed higher mineral filling than the other treatments. There was no difference between the treatments performed in the S group (p = 0.05). Otherwise, O-MLT had neoformed bone higher than in the other groups (p = 0.05). The groups that did not receive biomaterial demonstrated lower levels of Col-I secretion; S-MLT and S-MLTBO presented higher levels of OPN, while O-C presented statistically lower results (p < 0.05); O-BO showed greater BMP-2 secretion (p < 0.05). In the presence of ovariectomy-induced osteoporosis, MLT treatment increased the newly formed bone area, regulated the inflammatory response, and increased OPN expression. [ABSTRACT FROM AUTHOR]

In the current scenario, where demand for food production is constantly increasing with the rise in population, the threat of plant pathogens has also increased. The destruction of crops due to diseases caused by plant pathogens has become difficult to control with conventional physical and chemical methods. Traditional agriculture often depends on use of chemical pesticides, which have had negative impacts on both living organisms and ecosystems. As a fundamental principle of sustainable agriculture, it is important to limit the use of chemical pesticides in order to safeguard the environment and preserve diverse species. Additionally, sustainable agriculture should operate as a low input system, characterised by reduced production costs and increased net returns. Here, nanotechnology stands as a new weapon against rising challenges in agriculture. Nanotechnology may greatly improve the effectiveness of agricultural inputs, making it a valuable tool for promoting sustainable growth in agroecosystems via the use of nanoparticles. Using magnetic nanoparticles for controlling plant pathogenic fungi can be developed as a potent method for disease management in plants. In the present study, the effect of plant (Carica papaya) -based Fe3O4 magnetic nanoparticles was synthesized and studied against Fusarium oxysporum f.sp. ciceris, a chickpea pathogen. The antifungal effect of these nanoparticles and their minimum inhibitory concentration were studied using a soft agar assay and broth assay. Plant-synthesized nanoparticles were able to inhibit Fusarium oxysporum f.sp. ciceris by up to 87 %. It’s in vivo effect was checked with pot trials on chickpeas. Fe3O4 magnetic nanoparticles have shown adequate inhibition of fungus both in vitro and in vivo.

In this paper, the in vivo behavior of orthopedic implants covered with thin films obtained by matrix-assisted pulsed laser evaporation and containing bioactive glass, a polymer, and natural plant extract was evaluated. In vivo testing was performed by carrying out a study on guinea pigs who had coated metallic screws inserted in them and also controls, following the regulations of European laws regarding the use of animals in scientific studies. After 26 weeks from implantation, the guinea pigs were subjected to X-ray analyses to observe the evolution of osteointegration over time; the guinea pigs' blood was collected for the detection of enzymatic activity and to measure values for urea, creatinine, blood glucose, alkaline phosphatase, pancreatic amylase, total protein, and glutamate pyruvate transaminase to see the extent to which the body was affected by the introduction of the implant. Moreover, a histopathological assessment of the following vital organs was carried out: heart, brain, liver, and spleen. We also assessed implanted bone with adjacent tissue. Our studies did not find significant variations in biochemical and histological results compared to the control group or significant adverse effects caused by the implant coating in terms of tissue compatibility, inflammatory reactions, and systemic effects. [ABSTRACT FROM AUTHOR]

Amiodarone-induced thyrotoxicosis (AIT) is a common condition in patients who are receiving amiodarone for cardiac arrhythmia. This risk is elevated in iodine-deficient regions. Levothyroxine is the standard treatment for patients with hypothyroidism. This investigation is concerned with the evaluation of the possible pharmacokinetic interaction between amiodarone and levothyroxine upon co-therapy in rats and to investigate the cause of thyrotoxicosis. A selective, sensitive and precise RP-HPLC method was developed for the simultaneous determination of levothyroxine and amiodarone in rat plasma. A stationary phase of C18 Xterra RP column and a mobile phase consisting of acetonitrile: acidified water with 0.1% trifluoracetic acid (pH = 4.8) with gradient elution were used. The experiment was conducted at ambient temperature with flow rate of 1.5 mL/min for the chromatographic separation and quantitation of the investigated drugs. Protein precipitation with methanol was applied for the analysis of the two drugs in rat plasma. The method was linear over concentration range of 5–200 μg/mL for both levothyroxine and amiodarone. The European Medicines Agency guideline was applied for the validation of the developed bioanalytical method. The method was successfully applied to in vivo pharmacokinetic study in which levothyroxine and amiodarone were quantified in plasma of rats after receiving an oral dose of levothyroxine and amiodarone. After the calculation of the pharmacokinetic parameters, a statistical analysis was performed to elucidate the existence of significant difference between test and control groups in rats. The combination of levothyroxine and amiodarone significantly decreased levothyroxine bioavailability in rats, making the therapeutic drug monitoring mandatory in patients receiving levothyroxine and amiodarone. In addition, the increased clearance of levothyroxine upon the co-administration with amiodarone may explain the reported hypothyroidism. [ABSTRACT FROM AUTHOR]

Black shallot (Allium ascalonicum) is a variant of the common shallot, characterized by its distinctive dark purple-black skin and a milder, sweeter taste. Within the Allium genus, which includes garlic and onions renowned for their medicinal properties, back shallot has garnered attention for its potential health benefits. The current study specifically explores black shallot extract's analgesic and antipyretic effects. The analgesic potential of black shallot extract (EABS) was gauged using the hot plate test, Haffner tail clip test, writhing test induced by acetic acid, and formalin-induced pain test. The antipyretic effects of EABS were investigated using a yeastinduced fever model in mice. Concurrently, antipyretic effects were assessed through a yeastinduced fever model in mice. In pain models, EABS-treated mice demonstrated significantly prolonged reaction times (P < 0.05) compared to controls. All EABS doses exhibited maximum pain reduction effects (MPA) after 45 minutes (P < 0.05), indicating positive outcomes in the hot plate test. EABS efficiently alleviated pain, reaching peak efficacy within 10 minutes of the Haffner tail clip test (P < 0.05). Notably, EABS displayed superior pain reduction in both the acetic acid-induced writhing and formalin-induced pain tests. Furthermore, EABS consistently reduced rectal temperature (P < 0.05) throughout treatment, achieving a maximum antipyretic effect (63.24%) after 3 hours with a 200 mg/kg dose (P < 0.05). These findings provide robust evidence supporting the analgesic and antipyretic efficacy of EABS, underscoring its potential as a therapeutic option for pain and fever management. [ABSTRACT FROM AUTHOR]

Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p

This study aims to pharmacologically validate Haridra Khanda (HK) and Manjishthadi Kwatham (brihat) (MMK) in allergy management using invivo and invitro studies to rationalize the prescription of these two ayurvedic polyherbal drug formulations, which are currently used in Indian government hospitals. Experimental animals received HK and MMK orally from day 0 to day 14 and histamine (1 mg/kg b.w/i.v) and 1 % evans blue (EB) (0.1 mL) via tail vein on day 14. The compound 48/80 (intracutaneous) challenged mice model followed the same technique. The former mimicked acute anaphylaxis and the latter mast cell degranulation. For both models, EB dye leakage was quantified spectrophotometrically to determine vascular permeability. Plasma histamine was measured in Compound 48/80-induced animals using LC-ESI-MS/MS. The guineapig received HK and MMK p.o. and 0.6 % histamine sprayed in a histamine chamber to simulate allergic rhinitis. Blood eosinophil count and sneeze rate were measured in histamine-challenged guineapigs. Goat R.B.C. membrane stability assay (mammalian cell membrane toxicity) and intracellular histamine-induced cytosolic Ca2+ release assay in Chinese hamster ovary (CHO) cells were performed in vitro. For both histamine and Compound 48/80 challenged animals, HK (22.81 % and 14.58 %) and MMK (19.71 % and 22.40 %) significantly reduced EB dye leakage (p

AbstractNiosomes (NS) are the promising and novel carrier of the drug for effective transdermal delivery. Apigenin (AN) is a natural bioactive compound and has various pharmacological activities. AN is poorly water soluble which directly affects therapeutic efficacy. The aim of this research work was to develop the AN-NS gel to improve transdermal delivery. The thin-film hydration method was used for the development of AN-NS. The optimized AN-NS (AN-NS2) has a vesicle size of 272.56 ± 12.49 nm, PDI is 0.249, zeta potential is −38.7 mV, and entrapment efficiency of 86.19 ± 1.51%. The FTIR spectra of the AN-NS2 depicted that AN encapsulated in the NS matrix. AN-NS2 formulation was successfully incorporated into chitosan gel and evaluated. The optimized AN-NS2 gel (AN-NS2G4) has 2110 ± 14cps of viscosity, 10.40 ± 0.21g.cm/sec of spreadability, and 99.65 ± 0.53% of drug content. AN-NS2G4 displayed significantly (p

For the development of an effective and faster wound closure method, it is necessary to overcome current techniques' limitations. As compared to other methods, biodegradable staples provide superior mechanical properties, reduce scarring, and promote healing faster. Here, polylactic acid (PLA) and polyethylene glycol (PEG) composite staplers produced by solvent casting are presented as a suggestion for rapidly and easily closing wounds. The resulting samples were tested for mechanical properties, contact angle, and degradation properties over 21–90 days in the engineering phase. Selected formulations were moved to the biological phase for in vitro cytotoxicity by MTT assay and the in vivo biocompatibility assessment by transplantation of the samples into rats' back muscle. The tissue samples were collected and evaluated using hematoxylin and eosin and trichrome staining 1, 6, and 12 weeks after transplantation. When considering the maximum force tolerance range for PLA–PEG at around 20–58 N and comparing it with comparable commercial products, as well as their degradation rate and hydrophilicity, it was concluded that this combination maintains wound edges together. Cell viability tests demonstrated no cytotoxicity in the samples after 48 and 72 h. Morphological observations indicated some condensations of collagen fibers and no remarkable infiltration of inflammatory cells around the transplanted samples. In conclusion, the combination of PLA and PEG showed suitable mechanical properties, superior hydrophilicity, high biocompatibility and is suitable for medical staplers, and is innovative. [ABSTRACT FROM AUTHOR]

Objectives: The main objective of the study is to carry out comparative in vivo pharmacokinetic study of novel formulation with marketed formulation of lafutidine using HPLC method. Materials and Methods: The animals were selected according to the study protocol and divided in to three groups. The animals were given lafutidine marketed and novel formulation orally; at predetermined time blood samples were collected and subjected to the protein precipitation to collect blood plasma. The plasma samples were analysed using validated RP-HPLC method. Analysis of plasma was done at 215 nm using Hypersil silica, C18 250×4.6 mm. 5µ 0.02 M phosphate buffer and acetonitrile at 30:70 v/v was selected as mobile phase and passed at flow rate of 1.0 mL/min. Results: The established method was specific and sensitive for plasma sample. Calibration curve was developed using concentration range of 50-200 ng/mL with correlation coefficient 0.9993. The accuracy the intra and inter day precision was found 100.26 and 98.02% with percent accuracy 98.41% to 100.77% and 98.23% and 99.67%. Conclusion: The developed method is able to meet all specifications and reproducible to identify and quantify the lafutidine in rabbit plasma and can applied to study pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

The present study was designed to develop Aloe vera juice (100%), and further analyze its phenolics and flavonoids contents. Moreover, the developed Aloe vera juice was scrutinized for its antioxidant potential, radical scavenging capacity and also for efficacy study of lipid lowering potential in rat models. The results indicated that total phenolic contents were 821 ± 16.71gallic acid equivalents (GAE) /100 mL and total flavonoid contents were 89±4.94quercetin equivalent (QE) /100 mL. Maximum antioxidant activity of juice was found to be 34 ± 1.99 %. The radical scavenging assays showed 20.6 ± 1.97 %, 2.33 ± 0.4 µmol trolox equivalent (TE)/mL and 7.33 ± 2.01µmolTE/mL for DPPH, FRAP and ABTS, respectively. In addition, the lipid lowering effect of Aloe vera juice was assessed by in vivo study on rats as the level of cholesterol and triglycerides in serum was reduced to 21 % and 25.7 % respectively. Furthermore, the intake of juice significantly increased (18.3 %) the level of high-density lipoproteins and decreased (52 %) the level of low-density lipoproteins, indicating its positive role of lipid metabolism in the body. The liver enzymes (30-39 %) and oxidative stress indices i.e., superoxide dismutase, catalase and glutathione were also significantly improved in G-II. Therefore, in vivo efficacy studies validated the functional potential of Aloe vera juice against hyperlipidemia induced metabolic dysfunctions. Hence, the provision of locally processed aloe juice could remarkably lower the lipid profile. [ABSTRACT FROM AUTHOR]

Niosomes (NS) are the promising and novel carrier of the drug for effective transdermal delivery. Apigenin (AN) is a natural bioactive compound and has various pharmacological activities. AN is poorly water soluble which directly affects therapeutic efficacy. The aim of this research work was to develop the AN-NS gel to improve transdermal delivery. The thin-film hydration method was used for the development of AN-NS. The optimized AN-NS (AN-NS2) has a vesicle size of 272.56 ± 12.49 nm, PDI is 0.249, zeta potential is -38.7 mV, and entrapment efficiency of 86.19 ± 1.51%. The FTIR spectra of the AN-NS2 depicted that AN encapsulated in the NS matrix. AN-NS2 formulation was successfully incorporated into chitosan gel and evaluated. The optimized AN-NS2 gel (AN-NS2G4) has 2110 ± 14cps of viscosity, 10.40 ± 0.21g.cm/sec of spreadability, and 99.65 ± 0.53% of drug content. AN-NS2G4 displayed significantly (p<0.05) higher AN released (67.64 ± 3.03%) than pure AN-gel (37.31 ± 2.87%). AN-NS2G4 showed the Korsmeyer Peppas release model. AN-NS2G4 displayed significantly (p<0.05) higher antioxidant activity (90.72%) than pure AN (64.53%) at 300 mg/ml. AN-NS2G4 displayed significantly (p<0.05) higher % inhibition of swelling than pane AN-gel in carrageenin-induced paw oedema in rats. The finding concluded that niosomes-laden gel is a good carrier of drugs to improve transdermal delivery and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The chickpea is one of India's most protein-rich and low-input crops, yet it is plagued by a large number of soil-borne diseases. Fusarium wilt, which is brought on by Fusarium oxysporum f. sp. ciceris (FOC), can happen at any stage, from germination to fruiting, and it can drastically lower productivity. The purpose of this study was to ascertain the marine Bacillus subtilis's ability to serve as a biocontrol agent, and to examine its in vitro and in vivo impact on several vegetative parameters both in the presence and absence of pathogen FOC. Bacillus subtilis showed production of glucanase and effectively inhibited FOC in vitro. Bacillus subtilis was used to prepare a talc-based bio-formulation, and pot trials were conducted under three different conditions: control (T1), FOC treated (T2), and both Bacillus and FOC treated (T3). T3 showed 7.08% increase in plant weight whereas 1.20% increase in plant height in pot trials. Thus, it was able to improve plant growth despite presence of pathogen. Disease index was reduced from 3.2, without B. subtilis to zero in presence of B. subtilis. Additionally, it assisted in boosting several plant defense enzymes. It was also found to increase soil nitrogen, potassium and phosphate concentration as BS 90 is an ammonia producer and potassium and phosphate solubilizer. According to the findings, B. subtilis demonstrated bio-control abilities with inhibitory impact against FOC, protecting chickpea from disease. [ABSTRACT FROM AUTHOR]

Fermented soybean grain (FSBG) is considered improper to use as a protein source in animal nutrition, since it is assumed that defects cause changes on its chemical composition and favor mycotoxins production, but chemical composition data does not support this theory and in vivo studies are missing. Thus, this study aimed to evaluate the effects of FSBG in feedlot lamb diets. For that, two types of FSBG (partially fermented and completely fermented, PFSBG and CFSBG) and one standard soybean grain (SSBG) were obtained and evaluated alone or as a component of experimental diets by in vitro and in vivo studies, where FSBG totally replaced SSBG in feedlot lamb diets, which was included in the experimental diets in 17.4% on dry matter basis as protein source. Before the studies, both soybeans were sent to a specialized laboratory where no mycotoxins were detected. As a result, lower DM and carbohydrate contents but higher crude protein, fiber, and indigestible NDF contents were measured in CFSBG than in SSBG. Furthermore, both types of FSBG showed lower digestibility in vitro dry matter (IVDMD) than SSBG when evaluated separately; however, when evaluated in experimental diets, the substitution of SSBG for FSBG did not affect IVDMD. It was also observed that FSBG also had less rumen-degradable protein than SSBG (mean 47.9 vs 86.4%). In the in vivo study, FSBG did not affect nutrient intake, apparent digestibility, or animal performance (i.e., average daily gain and carcass gain). Thus, mycotoxins-free FSBG may be an alternative to totally replace SSBG in feedlot lamb diets. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles in vivo and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mgFe/kg, 45 mgFe/kg and 60 mgFe/kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance. [ABSTRACT FROM AUTHOR]

Because of the importance of gastric emptying for pharmacokinetics, numerous methods have been developed for its determination. One of the methods is the salivary tracer technique, which utilizes an ice capsule containing caffeine as a salivary tracer. Despite the ice capsule's advantage in labeling ingested fluids with caffeine for subsequent salivary detection, its risk of premature melting before swallowing, and its complicated storage and preparation, limit its application, particularly in special populations (e.g., older people). For this reason, here, a compression-coated tablet was developed and validated against the ice capsule in a cross-over clinical trial. The two dosage forms were administered simultaneously to 12 volunteers in an upright position under fasted and fed state conditions. To distinguish the caffeine concentrations in saliva from each dosage form, regular type of caffeine (12C) was added to the tablet, while for the ice capsule 13C3 labelled caffeine was used. The salivary caffeine concentrations showed no statistically significant differences for the pharmacokinetic parameters tmax and AUC0→60 (p > 0.05). Thus, the new formulation is a useful tool for determining gastric emptying that can also be used in special populations. [ABSTRACT FROM AUTHOR]

Introduction Polymethyl methacrylate (PMMA) is a common depot system in the treatment of chronic osteomyelitis. However, a lot of its shortcomings do not allow us to consider it ideal. Purpose of the work was to study in vivo the effectiveness of a polymer hydrogel containing an antibiotic for chronic osteomyelitis of the tibia in a rabbit model and compare it with PMMA Materials and methods The study was performed on the lower leg of 25 mature Chinchilla rabbits. A model of chronic osteomyelitis of the tibia was created. A methicillin-sensitive strain of Staphylococcus aureus (MSSA), highly active against cefazolin, was chosen as an infectious agent. Surgical debridement started 21 days after the clinical, laboratory, radiological and microbiological confirmation of the diagnosis, the technique for all animals was the same. The experimental group (n = 11) was treated by implantation of a polymer hydrogel, the comparison group (n = 11) with PMMA, and the control group (n = 3) had no implanted substance. In the postoperative period, monitoring of the local status, weight and body temperature of the animals, microbiological and radiological studies were carried out. Animals were taken out of the experiment by stages. Biopsies were sent for bacteriological and histomorphometric studies. Statistical comparison of the groups was performed using the Mann ‑ Whitney, Kruskell ‑ Wallis and Tukey criteria, descriptive statistics were used for the control group. Results In the experimental group, in all cases, postoperative wounds healed in a timely manner, the levels of WBC and CRP significantly (p = 0.040) decreased from 14 and 21 days, respectively. Microbiologically, the growth of microflora from the wound discharge and biopsy specimens was not detected; radiographic progression of chronic osteomyelitis was not observed; histomorphometry revealed a significant (p = 0.002) effective relief of the inflammatory process. In the comparison group, systemic antibiotic therapy was required from postoperative day 7. Levels of inflammatory markers decreased less effectively than in the experimental group. MSSA was verified from wound discharge and biopsy specimens at almost every follow-up time-point. X-rays and histomorphometry (p = 0.001), on average, detected exacerbation of osteomyelitis. In the control group, systemic therapy did not give positive dynamics. Discussion A comparative analysis showed that the hydrogel impregnated with an antibacterial agent, unlike PMMA, reliably arrests chronic osteomyelitis without auxiliary systemic antibiotic therapy and does not cause material-associated bone resorption. The clinical and laboratory picture is fully consistent with the data of microbiology, radiology and histomorphometry. Conclusion Hydrogel impregnated with an antibiotic reliably and effectively stops chronic osteomyelitis compared to PMMA.

Determining the safety of a newly developed experimental product is a crucial condition for its medical use, especially for clinical trials. In this regard, four hydrogel-type formulations were manufactured, all of which were based on carbomer (Blank-CP940) and encapsulated with caffeine (CAF-CP940), phosphorus derivatives (phenyl phosphinic (CAF-S1-CP940) and 2-carboxyethyl phenyl phosphinic acids (CAF-S2-CP940)). The main aim of this research was to provide a comprehensive outline of the biosafety profile of the above-mentioned hydrogels. The complex in vitro screening (cell viability, cytotoxicity, morphological changes in response to exposure, and changes in nuclei morphology) on two types of healthy skin cell lines (HaCaT—human keratinocytes and JB6 Cl 41-5a—murine epidermal cells) exhibited a good biosafety profile when both cell lines were treated for 24 h with 150 μg/mL of each hydrogel. A comprehensive analysis of the hydrogel’s impact on the genetic profile of HaCaT cells sustains the in vitro experiments. The biosafety profile was completed with the in vivo and in ovo assays. The outcome revealed that the developed hydrogels exerted good biocompatibility after topical application on BALB/c nude mice’s skin. It also revealed a lack of toxicity after exposure to the hen’s chicken embryo. Further investigations are needed, regarding the in vitro and in vivo therapeutic efficacy and safety for long-term use and potential clinical translatability.

The aim of this study was to evaluate the effect of local administration of melatonin (MLT) on molecular biomarkers and calvaria bone critical defects in female rats with or without osteoporosis, associated or not with a xenogeneic biomaterial. Forty-eight female rats were randomly divided into two groups: (O) ovariectomized and (S) placebo groups. After 45 days of osteoporosis induction, two critical-size defects (5 mm diameter) were created on the calvaria. The groups were subdivided according to the following treatment: (C) Clot, MLT, MLT associated with Bio-Oss® (MLTBO), and Bio-Oss® (BO). After 45 days, the defect samples were collected and processed for microtomography, histomorphometry, and biomolecular analysis (Col-I, BMP-2, and OPN). All animals had one femur harvested to confirm the osteoporosis. Microtomography analysis demonstrated a bone mineral density reduction in the O group. Regarding bone healing, the S group presented greater filling of the defects than the O group; however, in the O group, the defects treated with MLT showed higher mineral filling than the other treatments. There was no difference between the treatments performed in the S group (p = 0.05). Otherwise, O-MLT had neoformed bone higher than in the other groups (p = 0.05). The groups that did not receive biomaterial demonstrated lower levels of Col-I secretion; S-MLT and S-MLTBO presented higher levels of OPN, while O-C presented statistically lower results (p < 0.05); O-BO showed greater BMP-2 secretion (p < 0.05). In the presence of ovariectomy-induced osteoporosis, MLT treatment increased the newly formed bone area, regulated the inflammatory response, and increased OPN expression.

Dalia A Gaber,1 Amal M Alsubaiyel,1 Alanoud K Alabdulrahim,2 Hanan Z Alharbi,2 Rama M Aldubaikhy,2 Rawan S Alharbi,2 Wades K Albishr,2 Heba A Mohamed3 1Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah, 52571, Saudi Arabia; 2College of Pharmacy, Qassim University, Buraidah, 52571, Saudi Arabia; 3Department of Organic Chemistry, National Research Center, Giza, EgyptCorrespondence: Dalia A Gaber, Email dr_daliaahmed@hotmail.comIntroduction: Arthritic disorder is a common disease in elderly patients and the most common cause of joint dysfunction. This study aims to design Piroxicam-loaded nanoemulsion (PXM-NE) formulations to enhance the analgesic and anti-inflammatory activity of the drug for topical use.Methods: The nanoemulsion preparations were designed based on a high-pressure homogenization technique and were characterized for particle size (PS), poly dispersity index (Pi), zeta potential (ZP), drug content, and the selected formula was investigated for its topical analgesic activity and pharmacokinetic parameters.Results: The characterizations showed that the PS was 310.20± 19.84 nm, Pi was 0.15± 0.02, and ZP was − 15.74± 1.6 mV for the selected formula. A morphology study showed that the PXM-NE droplets were spherical with a uniform size distribution. The in vitro release study showed a biphasic release pattern with a rapid release within the first 2 hours followed by a sustained release pattern. The analgesic activity for optimal formula was 1.66 times higher than the commercial gel with a double duration of analgesic activity. The Cmax was 45.73± 9.95 and 28.48± 6.44 ng/mL for the gel form of the selected formula and the commercial gel respectively. The relevant bioavailability of the selected formula was 2.41 higher than the commercial gel.Conclusion: The results showed good physicochemical properties, higher bioavailability, and a longer analgesic effect of PXM from nanoemulsion gel, as compared to the commercial product.Keywords: analgesics, in vivo study, nanocarrier, drug efficacy, anti-inflammatory activity

The most severe chickpea diseases in the world is Fusarium wilt, which is brought on by the soil-borne fungus Fusarium oxysporum ciceris (FOC). FOC can reduce a chickpea crop's output by up to 100 %. Various management strategies have been employed out of which biological method is most suitable and effective. In the current study, the effectiveness of marine Bacillus licheniformis as a biocontrol agent against Fusarium infection in chickpea crops is investigated. Marine organisms are known to produce many antibiotics and controlling human pathogens. The current study aims at evaluating the effect of marine B. licheniformis against the chickpea pathogen (FOC). In vitro evaluations of glucanase and chitinase production as well as antifungal activity were done. B. licheniformis prevented development of fungal mycelia. Marine B. licheniformis was able to reduce disease index to 0 in chickpea. Three different conditions were used for the pot trial: control (T1), FOC treated (T2), and both Bacillus and FOC treated (T3). In pot experiment, T3 demonstrated 6.29 % increase in plant weight and 13.25 % increase in plant height. Despite the presence of FOC in T3, B. licheniformis was able to boost the growth of the plant while preventing FOC infection. The results showed that B. licheniformis has bio-control capabilities defending chickpea against disease and also improves its growth indicating that marine microbes are potent biocontrol agents. This study can open new avenues of using marine microbes in controlling plant disease.

Benzene, a potent carcinogen, is known to cause acute myeloid leukaemia. While chemotherapy is commonly used for cancer treatment, its side effects have prompted scientists to explore natural products that can mitigate the haematotoxic effects induced by chemicals. One area of interest is nano-theragnostics, which aims to enhance the therapeutic potential of natural products. This study aimed to enhance the effects of methanolic extracts from Ocimum basilicum, Rosemarinus officinalis, and Thymus vulgaris by loading them onto silica nanobeads (SNBs) for targeted delivery to mitigate the benzene-induced haematotoxic effects. The SNBs, 48 nm in diameter, were prepared using a chemical method and were then loaded with the plant extracts. The plant-extract-loaded SNBs were then coated with carboxymethyl cellulose (CMC). The modified SNBs were characterized using various techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), UV–visible spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The developed plant-extract-loaded and CMC-modified SNBs were administered intravenously to benzene-exposed rats, and haematological and histopathological profiling was conducted. Rats exposed to benzene showed increased liver and spleen weight, which was mitigated by the plant-extract-loaded SNBs. The differential white blood cell (WBC) count was higher in rats with benzene-induced haematotoxicity, but this count decreased significantly in rats treated with plant-extract-loaded SNBs. Additionally, blast cells observed in benzene-exposed rats were not found in rats treated with plant-extract-loaded SNBs. The SNBs facilitated targeted drug delivery of the three selected medicinal herbs at low doses. These results suggest that SNBs have promising potential as targeted drug delivery agents to mitigate haematotoxic effects induced by benzene in rats. [ABSTRACT FROM AUTHOR]

The similarities between thallium and potassium have suggested the use of calcium polystyrene sulfonate (CPS), an oral ion exchange resin, as a potential agent against thallium intoxication. Therefore, the study was an attempt to evaluate the efficacy of CPS and Prussian blue when given alone or in combination against thallium toxicity. The effect on binding capacity was investigated in terms of contact time, amount of CPS, influence of pH, simulated physiological solutions and interference of potassium ions. Also, rats were given single dose of thallium chloride (20 mg kg−1) and the treatment with PB and CPS was given for 28 days as CPS 30 g kg−1, orally, twice a day, PB 3 g kg−1, orally, twice a day and their combination. The effect of antidotal treatment was evaluated by calculating the thallium levels in various organs, blood, urine and feces. The results of the in vitro study indicated exceedingly quick binding in the combination of CPS and PB as compared to PB alone. Also, it was found that the binding capacity at pH 2.0 was considerably increased for PB with CPS (184.656 mg g−1) as compared to PB (37.771 mg g−1). Furthermore, statistically significant results were obtained in the in vivo study as after 7th day, thallium levels in blood of rats treated with combination were reduced by 64% as compared to control group and 52% as compared to alone PB treated group. Also, Tl retention in liver, kidney, stomach, colon and small intestine of combination treated rats was significantly reduced to 46%, 28%, 41%, 32% and 33% respectively, as compared to alone PB treated group. These findings demonstrate this as a good antidotal option against thallium intoxication. [ABSTRACT FROM AUTHOR]

Twenty novel phthalazinone‐based compounds were designed as acetylcholinesterase (hAChE) inhibitors. Compounds 7e and 17c demonstrated comparable or superior activity compared to donepezil, respectively, in in vitro enzyme assay. Moreover, both compounds 7e and 17c possess minimal toxicity on hepatic and neuroblastoma cell lines. Besides, it was proved that compounds 7e and 17c have percentage alternations and a transfer latency time comparable to donepezil and can alleviate the cognitive impairment caused by the scopolamine‐induced model in mice. The kinetic analysis for compound 17c suggested this compound as a mixed‐type inhibitor that could bind to both the peripheral (PAS) and the catalytic site (CAS) of the hAChE enzyme. The synthesized molecules were subjected to in silico analyses, including molecular docking studies, and the outcomes were consistent with the in vitro findings. [ABSTRACT FROM AUTHOR]

An ability to activate latent HIV-1 expression could benefit many HIV cure strategies, but the first generation of latency reversing agents (LRAs) has proven disappointing. We evaluated AKT/mTOR activators as a potential new class of LRAs. Two glycogen synthase kinase-3 inhibitors (GSK-3i's), SB-216763 and tideglusib (the latter already in phase II clinical trials) that activate AKT/mTOR signaling were tested. These GSK-3i's reactivated latent HIV-1 present in blood samples from aviremic individuals on antiretroviral therapy (ART) in the absence of T cell activation, release of inflammatory cytokines, cell toxicity, or impaired effector function of cytotoxic T lymphocytes or NK cells. However, when administered in vivo to SIV-infected rhesus macaques on suppressive ART, tideglusib exhibited poor pharmacodynamic properties and resulted in no clear evidence of significant SIV latency reversal. Whether alternative pharmacological formulations or combinations of this drug with other classes of LRAs will lead to an effective in vivo latency-reversing strategy remains to be determined.IMPORTANCE If combined with immune therapeutics, latency reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We have identified a new class of LRAs that do not induce T-cell activation and that are able to potentiate, rather than inhibit, CD8+ T and NK cell cytotoxic effector functions. This new class of LRAs corresponds to inhibitors of glycogen synthase kinase-3. In this work, we have also studied the effects of one member of this drug class, tideglusib, in SIV-infected rhesus monkeys. When tested in vivo, however, tideglusib showed unfavorable pharmacokinetic properties, which resulted in lack of SIV latency reversal. The disconnect between our ex vivo and in vivo results highlights the importance of developing next generation LRAs with pharmacological properties that allow systemic drug delivery in relevant anatomical compartments harboring latent reservoirs.

In this paper, the in vivo behavior of orthopedic implants covered with thin films obtained by matrix-assisted pulsed laser evaporation and containing bioactive glass, a polymer, and natural plant extract was evaluated. In vivo testing was performed by carrying out a study on guinea pigs who had coated metallic screws inserted in them and also controls, following the regulations of European laws regarding the use of animals in scientific studies. After 26 weeks from implantation, the guinea pigs were subjected to X-ray analyses to observe the evolution of osteointegration over time; the guinea pigs’ blood was collected for the detection of enzymatic activity and to measure values for urea, creatinine, blood glucose, alkaline phosphatase, pancreatic amylase, total protein, and glutamate pyruvate transaminase to see the extent to which the body was affected by the introduction of the implant. Moreover, a histopathological assessment of the following vital organs was carried out: heart, brain, liver, and spleen. We also assessed implanted bone with adjacent tissue. Our studies did not find significant variations in biochemical and histological results compared to the control group or significant adverse effects caused by the implant coating in terms of tissue compatibility, inflammatory reactions, and systemic effects.

Eriobotrya japonica (loquat tree) has been used in traditional medicine to treat respiratory ailments, inflammation, and skin diseases; however, its potential antidepressant-like effects have not been extensively investigated. In this study, we evaluated the antidepressant-like effects of E. japonica fruit extract (EJFE) in a mouse model of corticosterone (CORT)-induced depression. An HPLC analysis revealed that chlorogenic acid (CGA) is the major compound in EJFE. Male ICR mice (5weeks-old) were injected with CORT (40 mg/kg, intraperitoneally) once daily for 21 days to induce depressive-like behaviors. Various behavioral tests, including the open field test, rotarod test, elevated plus maze (EPM), passive avoidance test (PAT), tail suspension test (TST), and forced swim test (FST), were conducted 1 h after the oral administration of EJFE at different doses (30, 100, and 300 mg/kg) and CGA (30 mg/kg). High-dose EJFE and CGA significantly alleviated CORT-induced depressive-like behaviors, as indicated by the reduced immobility times in the TST and FST. A decrease in the step-through latency time in the PAT, without an effect on locomotor activity, suggested an improvement in cognitive function. Moreover, EJFE- and CGA-treated mice exhibited significantly reduced anxiety-like behaviors in the EPM. Our results imply the promising potential of EJFE containing CGA as a therapeutic candidate for depression. [ABSTRACT FROM AUTHOR]

Simple Summary: Gold nanoparticles have gained significant attention in the field of cancer research and treatment due to their unique properties and potential applications to medical imaging, targeted drug delivery, and combined use for cancer diagnosis and therapy. In this study, we developed novel gold nanoparticles with a bipyramidal shape, which have been functionalized to improve fluorescence imaging in the near-infrared biological window and facilitate the targeted delivery of chemotherapy to triple-negative breast tumors. We successfully tested these nanoparticle formulations in both in vitro and preclinical tumor models. Their ability to be combined with a wide range of fluorophores, therapeutics, and targeting agents demonstrates their clinical potential against various cancer types. There is an imminent need for novel strategies for the diagnosis and treatment of aggressive triple-negative breast cancer (TNBC). Cell-targeted multifunctional nanomaterials hold great potential, as they can combine precise early-stage diagnosis with local therapeutic delivery to specific cell types. In this study, we used mesoporous silica (MS)-coated gold nanobipyramids (MS-AuNBPs) for fluorescence imaging in the near-infrared (NIR) biological window, along with targeted TNBC treatment. Our MS-AuNBPs, acting partly as light amplification components, allow considerable metal-enhanced fluorescence for a NIR dye conjugated to their surfaces compared to the free dye. Fluorescence analysis confirms a significant increase in the dye's modified quantum yield, indicating that MS-AuNBPs can considerably increase the brightness of low-quantum-yield NIR dyes. Meanwhile, we tested the chemotherapeutic efficacy of MS-AuNBPs in TNBC following the loading of doxorubicin within the MS pores and functionalization to target folate receptor alpha (FRα)-positive cells. We show that functionalized particles target FRα-positive cells with significant specificity and have a higher potency than free doxorubicin. Finally, we demonstrate that FRα-targeted particles induce stronger antitumor effects and prolong overall survival compared to the clinically applied non-targeted nanotherapy, Doxil. Together with their excellent biocompatibility measured in vitro, this study shows that MS-AuNBPs are promising tools to detect and treat TNBCs. [ABSTRACT FROM AUTHOR]

Purpose: Achieving new contrast enhancer agents that can produce high-resolution images in magnetic resonance imaging (MRI) with a minimum dose and side effects has always been important. Methods: Herein, the pegylated curcumin-coated manganese–zinc ferrite nanoparticles (MZF@CA-PEG-CUR NPs) have been reported as an MR imaging nanoprobe in hepatocellular carcinoma detection in the murine model for the first time. In vitro studies were done on HEPA 1–6 cancer cells and L929 as normal cells, and in vivo studies were done on hepatocellular carcinoma (HCC) using xenograft models of HCC. Results: The prepared NP had a diameter of 105 nm with narrow size distribution and was superparamagnetic with a saturated magnetization (Ms) of 39 emu/g. The NP was biocompatible without any significant hemolysis and cytotoxicity. Prussian blue staining showed more cellular uptake of HEPA 1–6 compared to L929 control cells after incubation (P < 0.05). The concentration of Fe in mice blood confirmed the plasma half-life of about 3 h; it seems the PEGylation increased the circulation time. ICP-OES of Fe showed the highest tumor localization for MZF@CA-CUR-PEG NPs, due to passive accumulation, compared to the other mice studied organs. The r2 relaxivity of NPs was 134.89 mM− 1 s− 1, and in vitro MRI demonstrated better effects in HEPA 1–6 cells than in L929 (P < 0.05). Also, in vivo MR images showed signal enhancement efficacy in tumor-bearing mice. Conclusion: This study demonstrated that the MZF@CA-CUR-PEG nanoprobe could be a promising candidate as an MR imaging agent in hepatocellular carcinoma early detection. [ABSTRACT FROM AUTHOR]

Acute renal failure (ARF) is a deleterious condition with increased mortality or healthcare costs or dialysis-dependent end-stage renal disease. The study aims to compare prophylaxis with fondaparinux (Fund) vs. treatment with alteplase (Alt) in ameliorating cisplatin (Cis)-induced ARF. Sixty male mice were equally divided randomly into six groups of control, Cis, Alt, and Cis + Alt groups receiving normal saline for 10 days. All four groups except for the control received Cis (30 mg/kg, i.p.) on day 7, and 6 h later, both the Alt groups received Alt (0.9 mg/kg, i.v.). The animal groups Fund and Fund + Cis received Fund (5 mg/kg, i.p.) for 10 days, and the Fund + Cis group on day 7 received Cis. All the animal groups were euthanized 72 h after the Cis dose. The Fund + Cis group showed significantly increased expression levels of platelet count, retinoid X receptor alpha (RXR-α) and phosphorylated Akt (p-Akt) in addition to decreased levels of urea, blood urea nitrogen (BUN), uric acid, white blood cells (WBCs), red blood cells (RBCs), relative kidney body weight, kidney injury score, glucose, prothrombin (PT), A Disintegrin And Metalloproteinases-10 (ADAM10), extracellular matrix deposition, protease-activated receptor 2 (PAR-2), and fibrinogen expression when compared to the Cis-only group. Meanwhile, the Cis + Alt group showed increased caspase-3 expression in addition to decreased levels of urea, BUN, uric acid, WBCs, RBCs, glucose, platelet count and PT expression with a marked decrease in PAR-2 protein expression compared to the Cis group. The creatinine levels for both the Fund + Cis and Cis + Alt groups were found to be comparable to those of the Cis-only group. The results demonstrate that the coagulation system's activation through the stimulation of PAR-2 and fibrinogen due to Cis-induced ADAM10 protein expression mediated the apoptotic pathway, as indicated by caspase-3 expression through the p-Akt pathway. This is normally accompanied by the loss of RXR-α distal and proximal tubules as lipid droplets. When the animals were pre-treated with the anticoagulant, Fund, the previous deleterious effect was halted while the fibrinolytic agent, Alt, most of the time failed to treat Cis-induced toxicity. [ABSTRACT FROM AUTHOR]

Repaglinide and Metformin are used to treat Type 2 diabetes. Repaglinide with poor water solubility has relatively low oral bioavailability (56%) and undergoes hepatic first-pass metabolism. The oral bioavailability of metformin HCl is also low (about 50-60%). The purpose of this study was to prepare nanoemulsion formulations containing metformin HCl or repaglinide alone or in combination and characterize them in vitro and in vivo. Nanoemulsion formulations containing metformin HCl and/or repaglinide were successfully prepared and in vitro characterized. In addition, in vivo efficacy of nanoemulsion formulations was evaluated in a streptozotocin-nicotinamide-induced diabetic rat model. Biochemical, histopathological, and immunohistochemical evaluations were also performed. The mean droplet size and zeta potential values of nanoemulsion formulations were in the range of 110.15±2.64-120.23±2.16 nm and -21.95 – -24.33 mV, respectively. The percent entrapment efficiency values of nanoemulsion formulations were in the range of 93.600%-96.152%. All nanoemulsion formulations had a PDI of ≤0.223. A statistically significant decrease was observed in the blood glucose values of the diabetic rats treated with nanoemulsion formulations containing active substance/substances, compared to diabetic rats (control) (p<0.05). Nanoemulsion formulations (especially nanoemulsion containing metformin HCl and repaglinide combination) have a better antidiabetic activity and are more effective in reducing oxidative stress caused by diabetes. [ABSTRACT FROM AUTHOR]

Phytochemicals and naturally derived compounds, such as plant extracts and bee products, are regarded as complementary and alternative medicines for the treatment of skin wounds, due to their antibacterial, anti‐inflammatory, and antioxidant properties. In recent years, it has been shown that dressings impregnated with honey (particularly Manuka honey) are effective for the topical treatment of wounds and burns, and some of them are currently used in clinics. This has stimulated the development of more advanced dressings based on polymeric nanofibres that can release honey and other bee products (like propolis) to promote wound healing. In this review, the current literature on the electrospinning of honey and propolis is analyzed and the effectiveness of the resulting dressings to inhibit bacterial growth and stimulate cellular proliferation and tissue repair is discussed. [ABSTRACT FROM AUTHOR]

In recent years, zinc alloys have shown great potential as orthopedic plant materials because of their excellent biocompatibility, osteoinductive and biodegradation activities in vivo. The physiological function, degradation rate and mechanical properties of pure zinc were introduced in this review. Taking the gap between the above indicators and the clinical needs of orthopedics as the clue and the alloy elements as the classification basis, the existing achievements of researchers to improve the properties of zinc-based materials by changing the microstructure of materials and triggering the corresponding strengthening mechanism, and using the physiological synergistic function of added elements were expounded in this paper. The standard formulation, alloy design improvement and the introduction of new technologies such as additive manufacturing in the field of medical zinc based materials were discussed in order to meet the diversified needs of clinical diagnosis and treatment.

A myriad of health claims are being made in favor of the consumption of green tea due to its easy availability and greater popularity. On the contrary, certain health risks of excessive green tea consumption have begun to emerge. The aim of the present research was to observe the baleful effects of excessive green tea intake on hematological parameter and histoarchitecture of liver. A total of thirty (n=30) Swiss albino mice were taken and randomly divided into Control C, Treated T1, and Treated T2 groups. Each group consisted of ten (5 male+5 female) mice. The Control C group was fed with normal mice pellet and water (3ml/mice) orally but the treated T1 group was supplied mice pellet with 2ml/mice of green tea+1ml/mice of water orally as well as treated T2 group was given mice pellet and 3ml/mice of green tea orally two times in a day for 60 days. After the experimental tenure, mice of each group were sacrificed ethically and samples (Blood, liver and lungs) were collected for further hematological and histomorphological studies. Treated T2 group of mice were motionless (inactive and stagnant). Anatomopathologically, the liver surface became dark red in color with considerable hepatomegaly and mild hemorrhage also found on lung surface. Histologically, mild central vein congestion and severe venous congestion with dilation were found in the portal vein of the liver of the treated T2 group of mice. Hematologically, hemoglobin level significantly reduced in the treated T2 group of mice than the others. Within this experimental period, female mice of each group gave birth (15-18 pups) that were devoid of any abnormality. Therefore, it can be concluded that excessive green tea intake in a day might have baleful effects on hematological parameter (Hb concentration) and histoarchitechture of liver in Swiss albino mice.

INTRODUCTION: Anal traumas, such as blunt and penetrating injuries to the perineum, can disrupt the anal sphincter and cause considerable morbidity. Non-invasive anal trauma therapies have been widely developed, including growth factors administered as platelet-rich plasma (PRP) and stromal vascular fraction (SVFs) containing adiposederived stem cells (ASCs) and limited growth factor. This study aimed to assess PRP and SVF effects on capillary histopathology in the anal trauma Wistar rat model. MATERIALS AND METHODS: This experimental study used a rat model. Rats were divided into three groups: Group A (n=12) was treated with PRP and SVFs; Group B (n=12) was treated with normal saline (placebo); Group C (n=4) was sacrificed on day 0 to obtain baseline capillary counts. Groups A and B were further divided into three subgroups, sacrificed on days 1, 7, and 14 post-treatment. RESULTS: Capillary counts significantly showed higher density between Groups A and B (p=0.037, analysis of variance). On day 7, there was a significant difference between Groups A and B (p=0.001). CONCLUSION: Mean capillary density significantly improved in anal trauma treated with a combination of PRP and SVFs compared to control. Our findings support the use of PRP and SVFs to aid recovery of patients with anal trauma. [ABSTRACT FROM AUTHOR]

Scorpion venom contains various peptides that could be utilized to treat various diseases, including cancer. This study aimed to evaluate the anti-cancer activity of scorpion venom peptide (Smp24) using a solid Ehrlich Carcinoma (SEC) mice model. SEC model was established by subcutaneous transplantation of SEC cells into Swiss albino female mice afterward subcutaneous injection of the Smp24 peptide compared to 5-Fluorouracil (5-FU) as a standard drug. Various biochemical, hematological, histopathological, immunohistochemical, and molecular (western blotting and RT-PCR) assays were performed to evaluate the antitumor activity of Smp24. Results revealed that Smp24 peptide significantly reduced tumor volume. Interestingly, Smp24 peptide significantly restored normal body functions in cancer-treated groups by maintaining HB, RBC’s, and WBC’s levels, reducing the elevated serum ALT and AST, and increasing total protein and albumin as well as enhancing antioxidant status through reducing the level of MDA and NO and elevating GSH, SOD, and CAT levels. Moreover, it restored the normal morphology of the liver and kidney tissues and improved hematological parameters in cancer-treated animals. Smp24 induced apoptosis in SEC cells, through upregulation of caspase-3 and BAX and the downregulation of VEGF, Bcl-2, p53, PCNA, and Ki67. Moreover, results exhibited the apoptotic and antiangiogenic effects of Smp24 against SEC cancer cells. These findings supported our previous results about the anti-cancer efficacy of Smp24 and made it a good candidate for developing effective and safe anti-cancer agents. [ABSTRACT FROM AUTHOR]

Sparkling water is said to increase gastric motility by the release of carbon dioxide, thereby potentially affecting the pharmacokinetics of orally administered drugs. The hypothesis of the present work was that the induction of gastric motility by intragastric release of carbon dioxide from effervescent granules could promote the mixing of drugs into the chyme under postprandial conditions, resulting in a prolonged drug absorption. For this purpose, an effervescent and a non-effervescent granule formulation of caffeine as a marker for gastric emptying were developed. In a three-way crossover study with twelve healthy volunteers, the salivary caffeine pharmacokinetics, after administration of the effervescent granules with still water and the administration of the non-effervescent granules with still and sparkling water, were investigated after intake of a standard meal. While the administration of the effervescent granules with 240 mL of still water led to a significantly prolonged gastric residence of the substance compared to the administration of the non-effervescent granules with 240 mL still water, the application of the non-effervescent granules with 240 mL sparkling water did not prolong gastric residence via mixing into caloric chyme. Overall, the mixing of caffeine into the chyme following the administration of the effervescent granules did not seem to be a motility mediated process. [ABSTRACT FROM AUTHOR]