Search

One of the major concerns for all in vivo experiments is intra- and inter-subject variability, which can be a great source of inaccuracy. The aim of this study is, therefore, to estimate the ability of parallel vs. cross-over design studies in order to describe the relative pharmacokinetic performance of the studied drug formulations. We analyzed the data from a drug development program that examined the performance of innovative abiraterone acetate formulations against the identical reference product in three stages. In stages 1–3, groups A–F were dosed with the reference product once in a parallel manner. Stage 4 was performed to evaluate the intra-individual variability (IIV) by repeated administration of the reference product to the same animals. Although the geometric mean (90% CI) values of abiraterone AUClast in groups A–F were similar to the IIV group (24.36 (23.79–41.00) vs. 26.29 (20.56–47.00) mg/mL·min·g), the results generated in the isolated parallel groups provided imprecise estimates of the true AUClast values ranging from 9.62 to 44.62 mg/mL·min·g due to chance. Notably, in 4 out of 15 possible pair comparisons between the parallel groups, the confidence intervals did not include 100%, which is the true ratio for all comparisons tested after identical formulation administration to all groups. A cross-over design can significantly improve the methodology in short-term comparative pre-clinical pharmacokinetic studies, and can provide more precise and accurate results in comparison to more traditional pre-clinical study designs. [ABSTRACT FROM AUTHOR]

Plasma‐activated media (PAM), the product of cold atmospheric plasma (CAP) acting on aqueous media, has similarly strong biological activity and some unique advantages compared with CAP for biomedical targets. However, no reliable PAM‐preparing device with high safety for medical uses has yet been developed, limiting the advancement of PAM clinical trials. Herein, an integrated device for PAM preparation with a maximum yield of 4.8 L/hr is reported in detail. A large‐area CAP is generated by the plasma‐generating module based on the surface dielectric barrier discharge. Several sensors and controllers are applied in this device to stabilize the discharge environment and PAM consistency. In the in vitro experiments, PAM prepared in this device exhibits the bactericidal property of up to 6 logs reduction against various clinical pathogens with multi‐drug resistance. The high bactericidal effect of PAM can be preserved for ∼10 min. After constructing the mice model by cecal ligation and puncture, it is found that the abdominal injection of PAM can effectively relieve sepsis‐induced systemic toxicity and maintain homeostasis, which is mainly attributed to the anti‐infective efficacy of PAM. The third‐party testing confirms that the soaking bactericidal rates of PAM to S. aureus and E. coli are respectively higher than 99.99% and 99.999%, while the acute oral toxicity, skin irritation, and oral genotoxicity of PAM are negligible. This study provides a practical approach for preparing PAM with high reliability, which shows an excellent prospect of clinical applications and commercialization. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major cause of death in tropical countries such as Nigeria. Chasmanthera dependens (Hochst) is a wild plant used by traditional healers for the treatment of malaria and other health challenges. This study evaluated the 'Antiplasmodial and in vitro antioxidant potentials of crude aqueous and methanol extracts of leaves, root and stem of Chasmanthera dependens (Hochst)'. Results: Methanol extracts of leaves and roots of this plant exhibited higher antimalarial activities than other extracts. The level of parasitemia was significantly (p < 0.05) reduced in the treated animals when compared to untreated ones. Antiplasmodial activities of methanol extracts of roots and stem did not differ significantly (p < 0.05) from their aqueous extracts. An increase in body weight and higher survival rates were recorded in all the treated groups. Scavenging of DPPH, NO, H2O2 radicals and reducing power ability were concentration-dependent. Methanolic extracts of C. dependens root showed the best reducing activity. Phytochemical analyses revealed the presence of tannins, saponins, alkaloids, terpenoids, cardiac glycosides, flavonoids, phenols, phytate and oxalate. Conclusion: Antimalarial and antioxidant properties of these extracts could be credited to the synergy between the phytoconstituents in this plant. Findings from this study justified the use of this plant in the treatment of malaria and other ailments. [ABSTRACT FROM AUTHOR]

Poor solubility, low bio-stability, and the high toxicity of docetaxel medicine result in limited consumption, common side effects, and low efficacy. The current commercial form of the product, Taxotere®, with intravenous administration caused hypersensitivity due to hemolysis by separating hemoglobin and red blood cells. In addition, the patient suffers from a severe treatment regime through prolonging medicine injection. The most important advantages of medicine in cancer treatment are to consider patients' comfort, and acceptance during treatment, as well as to choose the most effective medicine to achieve the highest improvement in cancer cells. Following our previous study, in this study stabilized docetaxel loaded nanomicelles were used for the treatment of mice with C26 colon carcinoma. The synthesized nanomicelles have satisfying results on animal trials and adequate characters such as an oral form of medicine, particle size of less than 15 nm, proper PDI, sufficient zeta potential for physical stability and maintaining particle size, non-toxicity of career, and high efficacy than the commercial product Taxotere®. In addition, lower side effects of synthesized oral form medicine on the treatment of C26 colon carcinoma can be named as the other advantage of this study.

Background: Exposure to small confined spaces evokes physiological responses such as increased heart rate in claustrophobic patients. However, little is known about electrocortical activity while these people are functionally exposed to such phobic situations. The aim of this study was to examine possible changes in electrocortical activity in this population. Method: Two highly affected patients with claustrophobia and two healthy controls participated in this in vivo study during which electroencephalographic (EEG) activity was continuously recorded. Relative power spectral density (rPSD) was compared between two situations of being relaxed in a well-lit open area, and sitting in a relaxed chair in a small (90 cm × 180 cm × 155 cm) chamber with a dim light. This comparison of rPSDs in five frequency bands of EEG was intended to investigate possible patterns of change in electrical activity during fear-related situation. This possible change was also compared between claustrophobic patients and healthy controls in all cortical areas. Results: Statistical models showed that there is a significant interaction between groups of participants and experimental situations in all frequency bands (P < 0.01). In other words, claustrophobic patients showed significantly different changes in electrical activity while going from rest to the test situation. Clear differences were observed in alpha and theta bands. In the theta band, while healthy controls showed an increase in rPSD, claustrophobic patients showed an opposite decrease in the power of electrical activity when entering the confined chamber. In alpha band, both groups showed an increase in rPSD, though this increase was significantly higher for claustrophobic patients. Conclusion: The effect of in vivo exposure to confined environments on EEG activity is different in claustrophobic patients than in healthy controls. Most of this contrast is observed in central and parietal areas of the cortex, and in the alpha and theta bands.

Aim To compare the clinical performance of composite restorations placed with a universal adhesive, one-step and two-step self-etch adhesives in class I and II posterior cavities. Materials and methods In this in vivo study, 46 volunteers presenting with at least three carious lesions were included. Each participant received the three restorative systems: universal adhesive/nanofilled composite (Scotchbond Universal/Filtek Z350 XT: SBU/FZXT), one-step self-etch adhesive/microhybrid composite (G-aenial bond/G-aenial Posterior: GB/GP) and the two-step self-etch adhesive/nanohybrid composite (OptiBond XTR/Herculite Ultra: OBX/HU). The adhesives were all placed in self-etch mode. In total, 138 restorations were evaluated at baseline and at 6,12 and 36 months using the modified United States Public Health Service criteria. Data were analysed using Kruskal–Wallis, Mann–Whitney U, Friedman and Wilcoxon non-parametric tests (p

Aim of study. The study is devoted to the effect of L-lysine aescinat on the nervous tissue of the CA1 and CA3 fields of the hippocampus of the brain of white rats in the acute period after severe traumatic brain injury (TBI).Material and methods. TBI was simulated by applying a blow to the parieto-occipital region with a freely falling weight weighing 200-250 grams from a height of 50 cm using a special rail rack. The objectives of the study were: 1) comparative morphometric assessment of the degree of hydration, cyto- and glioarchitectonics of different layers of CA1 and CA3 fields after ischemia without treatment; 2) the effect of L-lysine aescinat on these indicators. We used histological (staining of sections with hematoxylin-eosin and Nissl), immunohistochemical (for NSE, MAP-2 and GFAP) and morphometric methods. On thin (4 μm) serial frontal sections of the hippocampus, neurons, astrocytes, microvessels and neuropiles were studied in control (intact animals, n=5) and 1 and 3 days after injury without treatment (n=10, comparison group) and with treatment ( n = 10, main group). The number density of neurons was determined using the Nissl staining of cells and by the reaction to NSE. The cytoskeleton of neurons was studied by detecting MAP-2, and astroglia by GFAP. On color raster images (staining with hematoxylin and eosin, x100) using the Find Maxima plug-in filter, the zones of maximum brightness were determined, which were then analyzed using Analyze Particles from the ImageJ 1.52s program. Zones of maximum brightness corresponded to areas of the hippocampus with a high degree of hydration of the nervous tissue - edema-swelling. The nature of the distribution, statistical hypotheses, and plotting were checked using Statistica 8.0 software and R environment.Results. In control animals, normochromic neurons without signs of changes in the cytoskeleton prevailed in all layers of fields CA1 and CA3, and a low degree of hydration of the nervous tissue was noted (the relative proportion of zones of maximum brightness was 5–8%). One and 3 days after TBI, there was a statistically significant increase in the focal content of dystrophic and necrobiotically altered neurons (95% confidence interval: 52–78%), manifestations of reactive gliosis were noted, and the proportion of zones of maximum brightness increased to 16%. Statistically significant layer-by-layer differences were revealed between the CA1 and CA3 fields of the hippocampus. The use of L-lysine aescinat had a statistically significant effect on the morphometric parameters of the nervous tissue of the hippocampus.Conclusion. In the early post-traumatic period after TBI, the degree of hydration of the nervous tissue of the hippocampus increased. Heteromorphicity of dystrophic and necrobiotic changes in different layers of CA1 and CA3 fields was noted. L-lysine aescinate had a statistically significant positive effect on these changes. To a greater extent, this is typical for the CA3 field. The revealed changes are considered not only as patho-, but also as sanogenetic structural mechanisms of protection and reorganization of the hippocampus in the acute post-traumatic period.1. In the acute period (1−3 days) after severe traumatic brain injury, the degree of hydration of all components of the hippocampal nervous tissue increased. In the group without treatment, 3 days after injury, the relative volume of edema-swelling zones varied from 10 to 13% in CA1 (control 3-7%) and from 8 to 16% in CA3 (control 5–10%).2. The heteromorphism of hydropic changes in the molecular layer, the layer of pyramidal neurons and the polymorphic layer was established. The maximum increase in the volume of free water (more than twofold) was characteristic of the molecular and polymorphic layer CA1, as well as the polymorphic layer CA3.3. The use of L-lysine aescinat in the acute period significantly changed the manifestations of hydropic dystrophy. One day after injury, the volume of free water increased in comparison with animals without treatment, and then, after 3 days, decreased, but remained higher than in the comparison group. The maximum effect of the drug was noted in field CA3.

Qiang Chi, Hui Xu, Dianbin Song, Zhiyong Wang, Zemin Wang, Guang Ma Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde 067000, People’s Republic of ChinaCorrespondence: Qiang ChiDepartment of Urology, Affiliated Hospital of Chengde Medical University, Chengde 067000, People’s Republic of ChinaTel +86-18732471770Email chi_qiang.2007@163.comAim: Bladder cancer (BLCA) is an urogenital system tumor with a high morbidity. We aimed to explore the function and potential mechanism of α-E-catenin (CTNNA1) in BLCA.Methods: The CTNNA1 expression in BLCA tissues was detected using qRT-PCR and immunohistochemistry. QRT-PCR and Western blot were performed to measure the CTNNA1 expression in BLCA cell lines. CTNNA1 expression was up-regulated in T24 and UMUC-2 cells by CTNNA1 overexpression plasmid transfection. Cell proliferation, apoptosis, migration and invasion were respectively assessed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. The expression levels of epithelial–mesenchymal transition (EMT)-related factors were tested by qRT-PCR and Western blot. BLCA nude mice models were constructed to explore the effects of CTNNA1 on BLCA in vivo. Gene set enrichment analysis (GSEA) was proceeded to identify the CTNNA1-related pathways in BLCA.Results: The expressions of CTNNA1 were down-regulated in BLCA tissues and cell lines, and its low expression indicated poor prognosis of BLCA patients. CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA cells. CTNNA1 enhanced E-cadherin expression and suppressed N-cadherin, snail, MMP2 and MMP9 expressions in BLCA cells, which suggested that CTNNA1 repressed EMT in BLCA cells. Moreover, CTNNA1 could inhibit tumor growth in vivo. CTNNA1 was positively associated with P53 and apoptosis pathways in BLCA cells.Conclusion: CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA via activating P53 and apoptosis pathways. CTNNA1 might be a novel target in BLCA therapy.Keywords: bladder cancer, CTNNA1, cell proliferation, in vivo study, GSEA

The aim of this study was to investigate the biocompatibility and osteoinductive properties of fibrous scaffolds implanted in the bone tissue of white rats in vivo. The effect of various concentrations of conductive PANi (2 and 3 wt%) and rGO (0.2 and 1 wt%) in the PHB scaffolds on the reparative processes of bone callus formation in white rats was studied. On the 28th day after implantation, a histomorphological study of the preparations of the transverse section of the diaphysis of the femur of the implantation area was performed. The results of implantation tests in the femur revealed that all the studied scaffolds are biocompatible and the most pronounced stimulating effect on bone formation was observed for hybrid PHB scaffolds doped with 3 wt% PANi and 0.2 wt% rGO compared with pure PHB scaffolds, thus determining further prospects to study the osteoinductive features of hybrid PHB scaffolds.

Introduction: Colorectal cancer is the third most common malignancy and the second most deadly cancer worldwide. In this present study, the effects of eupafolin on DMH-induced colon cancer in rats were assessed. Methods: The acute and sub-acute oral toxicity study in the balb/c mice was performed to evaluate the LD50 dose and the chemotherapeutic doses of eupafolin. The colon cancer was induced in the animals through a single intraperitoneal injection (i.p) of 30 mg/kg of dimethylhydrazine followed by 2% DSS for 7 days in the drinking water in male Wistar rats. The rats were treated with eupafolin (50, 100, and 200 mg/kg) through oral route for 18 weeks. The animals were sacrificed and colon tissues were subsequently investigated for aberrant crypt foci (ACF), in vivo antioxidant studies, histology and immunohistochemical analysis, and apoptosis by TUNNEL technique after 18 weeks of eupafolin therapy. Results: The acute oral toxicity data represented the LD50 dose of eupafolin which was found to be 500 mg/kg body weight. Along with that, the sub-acute toxicity study suggested the chemotherapeutic doses of eupafolin, that is, 50, 100, and 200 mg/kg body weight. Eupafolin therapy inhibits ACF development in rat colon mucosa efficiently. Additionally, eupafolin has improved the colonic lesions and the structural integrity of the colonic mucosa. Eupafolin therapy causes anti-oxidant enzymes such as superoxide dismutase, catalase, and glutathione to increase as well. Increased levels of P53, BAX, and PCNA and a simultaneous decrease in Bcl2 and IL-6 expressions show eupafolin therapy successfully regulated these biological markers in colorectal cancer. Eupafolin also induced apoptosis efficiently in the rat colon mucous membrane. Conclusion: These results show that eupafolin can improve colon cancer by modulating the p53, Bcl2, BAX, and IL-6 pathways in rats. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer is the third most common malignancy and the second most deadly cancer worldwide. In this present study, the effects of eupafolin on DMH-induced colon cancer in rats were assessed. Methods: The acute and sub-acute oral toxicity study in the balb/c mice was performed to evaluate the LD50 dose and the chemotherapeutic doses of eupafolin. The colon cancer was induced in the animals through a single intraperitoneal injection (i.p) of 30 mg/kg of dimethylhydrazine followed by 2% DSS for 7 days in the drinking water in male Wistar rats. The rats were treated with eupafolin (50, 100, and 200 mg/kg) through oral route for 18 weeks. The animals were sacrificed and colon tissues were subsequently investigated for aberrant crypt foci (ACF), in vivo antioxidant studies, histology and immunohistochemical analysis, and apoptosis by TUNNEL technique after 18 weeks of eupafolin therapy. Results: The acute oral toxicity data represented the LD50 dose of eupafolin which was found to be 500 mg/kg body weight. Along with that, the sub-acute toxicity study suggested the chemotherapeutic doses of eupafolin, that is, 50, 100, and 200 mg/kg body weight. Eupafolin therapy inhibits ACF development in rat colon mucosa efficiently. Additionally, eupafolin has improved the colonic lesions and the structural integrity of the colonic mucosa. Eupafolin therapy causes antioxidant enzymes such as superoxide dismutase, catalase, and glutathione to increase as well. Increased levels of P53, BAX, and PCNA and a simultaneous decrease in Bcl2 and IL-6 expressions show eupafolin therapy successfully regulated these biological markers in colorectal cancer. Eupafolin also induced apoptosis efficiently in the rat colon mucous membrane. Conclusion: These results show that eupafolin can improve colon cancer bymodulating the p53, Bcl2, BAX, and IL-6 pathways in rats. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cartilage tissue lacks the ability to heal. Cartilage tissue engineering using cell-free scaffolds has been increasingly used in recent years. OBJECTIVE: This study describes the use of a type I collagen scaffold combined with WNT5A plasmid to promote chondrocyte proliferation and differentiation in a rabbit osteochondral defect model. METHODS: Type I collagen was extracted and fabricated into a collagen scaffold. To improve gene transfection efficiency, a cationic chitosan derivative N,N,N-trimethyl chitosan chloride (TMC) vector was used. A solution of TMC/WNT5A complexes was adsorbed to the collagen scaffold to prepare a WNT5A scaffold. Osteochondral defects were created in the femoral condyles of rabbits. The rabbits were divided into defect, scaffold, and scaffold with WNT5A groups. At 6 and 12 weeks after creation of the osteochondral defects, samples were collected from all groups for macroscopic observation and gene expression analysis. RESULTS: Samples from the defect group exhibited incomplete cartilage repair, while those from the scaffold and scaffold with WNT5A groups exhibited "preliminary cartilage" covering the defect. Cartilage regeneration was superior in the scaffold with WNT5A group compared to the scaffold group. Safranin O staining revealed more proteoglycans in the scaffold and scaffold with WNT5A groups compared to the defect group. The expression levels of aggrecan, collagen type II, and SOX9 genes were significantly higher in the scaffold with WNT5A group compared to the other two groups. CONCLUSIONS: Type I collagen scaffold showed effective adsorption and guided the three-dimensional arrangement of stem cells. WNT5A plasmid promoted cartilage repair by stimulating the expression of aggrecan, type II collagen, and SOX9 genes and proteins, as well as inhibiting cartilage hypertrophy. [ABSTRACT FROM AUTHOR]

The formation of biofilms on the surface of dental implants and abutment materials may lead to peri-implantitis and subsequent implant failure. Recently, innovative materials such as polyether-ether-ketone (PEEK) and its modifications have been used as abutment materials. However, there is limited knowledge on microbial adhesion to PEEK materials. The aim of this in vivo study was to investigate biofilm formation on the surface of conventional (titanium and zirconia) and PEEK implant abutment materials. Split specimens of titanium, zirconia, PEEK, and modified PEEK (PEEK-BioHPP) were manufactured, mounted in individual removable acrylic upper jaw splints, and worn by 20 healthy volunteers for 24 h. The surface roughness was determined using widefield confocal microscopy. Biofilm accumulation was investigated by fluorescence microscopy and quantified by imaging software. The surface roughness of the investigated materials was p < 0.001) between the investigated materials, except for the polyether-ether-ketones. Generally, biofilm formation was significantly higher (p < 0.05) in the posterior region of the oral cavity than in the anterior region. The results of the present study show a material-dependent susceptibility to biofilm formation. The risk of developing peri-implantitis may be reduced by a specific choice of abutment material.

Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage. This review aimed to evaluate the benefits of lycopene supplementation in cancer prevention and treatment based on the results of in vivo studies. We identified 72 human and animal studies that were then analysed for endpoints such as cancer incidence, improvement in treatment outcomes, and the mechanisms of lycopene action. We concluded that the results of most of the reviewed in vivo studies confirmed the anti-cancer activities of lycopene. Most of the studies concerned prostate cancer, reflecting the number of in vitro studies. The reported mechanisms of lycopene action in vivo included regulation of oxidative and inflammatory processes, induction of apoptosis, and inhibition of cell division, angiogenesis, and metastasis formation. The predominance of particular mechanisms seemed to depend on tumour organ localisation and the local storage capacity of lycopene. Finally, there is a need to look for predictive factors to identify a population that may benefit from lycopene supplementation. The potential candidates appear to be race, single nucleotide polymorphisms in carotene-cleaving enzymes, some genetic abbreviations, and insulin-like growth factor-dependent and inflammatory diseases.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kazmi, Fatima, Naz, Kanwal and Haq.)

Zinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models. In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for their osteogenic activity both in vitro and in vivo. The ZnO MBGs showed excellent textural properties despite ZnO incorporation. However, the release of Zn2+ ions inhibited the mineralization process when immersed in simulated body fluid. In vitro assays showed significantly higher values of viability and expression of early markers of cell differentiation and angiogenesis in a ZnO-content-dependent manner. The next step was to study the osteogenic potential in a sheep bone defect model. Despite their excellent textural properties and cellular response in vitro, the ZnO MBGs were not able to integrate into the bone tissue, which can be explained in terms of inhibition of the mineralization process caused by Zn2+ ions. This work highlights the need to develop nanostructured materials for bone regeneration that can mineralize to interact with bone tissue and induce the processes of implant acceptance, cell colonization by osteogenic cells, and regeneration of lost bone tissue.

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 Ca 2+ 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 < 0.05). Both formulations, HK and MMK considerably (p < 0.05) decreased plasma histamine (29.62 % and 25.37 % respectively) in mice and eosinophilic count (11.56 % and 9.94 % respectively) and sneeze rate (42.58 % and 29.03 % respectively) in guinea pigs. In membrane stability experiment, HK and MMK reduced RBC lysis. Both HK and MMK raw/dialysate blocked CHO cell cytosolic Ca 2+ release. HK and MMK activities mimic mast cell stabilization with possible H1 receptor inactivation seen by decreased Ca 2+ efflux and thus indicate potential for allergic rhinitis management. The combination of activities is usually related with curative and prophylactic therapy and might lead future clinical trials and therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Exposure to small confined spaces evokes physiological responses such as increased heart rate in claustrophobic patients. However, little is known about electrocortical activity while these people are functionally exposed to such phobic situations. The aim of this study was to examine possible changes in electrocortical activity in this population. Method: Two highly affected patients with claustrophobia and two healthy controls participated in this in vivo study during which electroencephalographic (EEG) activity was continuously recorded. Relative power spectral density (rPSD) was compared between two situations of being relaxed in a well-lit open area, and sitting in a relaxed chair in a small (90 cm × 180 cm × 155 cm) chamber with a dim light. This comparison of rPSDs in five frequency bands of EEG was intended to investigate possible patterns of change in electrical activity during fear-related situation. This possible change was also compared between claustrophobic patients and healthy controls in all cortical areas. Results: Statistical models showed that there is a significant interaction between groups of participants and experimental situations in all frequency bands (P < 0.01). In other words, claustrophobic patients showed significantly different changes in electrical activity while going from rest to the test situation. Clear differences were observed in alpha and theta bands. In the theta band, while healthy controls showed an increase in rPSD, claustrophobic patients showed an opposite decrease in the power of electrical activity when entering the confined chamber. In alpha band, both groups showed an increase in rPSD, though this increase was significantly higher for claustrophobic patients. Conclusion: The effect of in vivo exposure to confined environments on EEG activity is different in claustrophobic patients than in healthy controls. Most of this contrast is observed in central and parietal areas of the cortex, and in the alpha and theta bands. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthetic amorphous silica is the authorized food additive Silicon dioxide or E551. • A 90-day oral toxicity study was performed at dose levels close to human exposure through E551. • Male reproductive system is not target showing no histophatological or genotoxic effects. • In female no histophatological/genotoxic effects in ovary and limited effects in uterus. • The study identified a limited concern only for female reproductive health. Synthetic amorphous silica (SAS) consists of agglomerates and aggregates of primary particles in the nanorange (<100 nm) and it is the E551 authorized food additive. The potential risks for human health associated to dietary exposure to SAS are not completely assessed; in particular, data on male and female reproductive systems are lacking. A 90-day oral toxicity study with pyrogenic SAS nanomaterial NM-203 was carried out on the basis of the OECD test guideline 408 in the frame of the NANoREG project. Adult Sprague-Dawley rats of both sexes were orally treated for 90 days with 0, 2, 5, 10, 20 and 50 mg SAS/kg bw per day. Dose levels were selected to be as close as possible to the expected human exposure to food additive E551. The present paper provides specific information on potential effects on male and female reproductive systems, through the evaluation of serum biomarkers, sperm count, histopathological analysis of testis, epididymis, ovary and uterus and real-time PCR on uterus; potential genotoxic alterations were evaluated by comet assay on testis, sperm and ovary. NM-203 did not induce histophatological and genotoxic effects in male reproductive system. In female rats, ovary is not target of NM-203 and only tissue-specific effects on uterus were recorded up to 10 mg/kg bw per day. To our best knowledge, this is the first study providing data on male and female reproductive systems after long-term, repeated oral exposure at dose levels close to dietary human exposure, which identifies a limited concern only for female reproductive health. [ABSTRACT FROM AUTHOR]

Aim/Background: There is an increasing prevalence of diabetes mellitus throughout the world, and new compounds are necessary to combat this. While the current available antidiabetic therapies are long-term complicated and side effects-prone, this has led to a demand for more affordable, more effective methods of tackling diabetes. Research is focused on finding alternative medicinal remedies with significant antidiabetic efficacy as well as low adverse effects. This study synthesized, characterized, and evaluated anti-diabetic properties of synthetic sulphonamide hybrid of 1,3,4-oxadiazole derivatives. Materials and Methods: An in vivo antihyperglycemic evaluation of the sulphonamide hybrid of 1,3,4-oxadiazole derivatives was conducted using wistar rat models of type II diabetes derived from a two-step synthesis. Our study examined the effects of synthesized compounds on a model induced by a high-fat diet combined with streptozotocin and nicotinamide injection. For assessment of diabetic effects, Vildagliptin (10 mg/kg/day) was used as the standard drug. On day 14th, 1,3,4-oxadiazole derivatives (50 mg/kg/day) significantly lowered the blood sugar of hyperglycemic rats. Results: Due HFD STZ with Nicotinamide blood glucose level of wistar rat was increased (295 ± 8.2). After 14th day administration of derivatives random blood glucose level under controlled. A-III (220± 7.5 B) and A-IV (222 ± 3.62 B) were lowered random blood glucose levels on wistar rat. As compared to diabetes control (295 ± 8.5), derivatives of 1,3,4-oxadiazole are considered promising lead compounds. Compounds A-III and A-IV were found to be the most effective in lowering blood glucose, indicating the potential of these compounds as antidiabetic agents. Conclusion: Hybrids developed in this study provide new classes of anti-diabetic agents, and further optimization can be performed using this information. [ABSTRACT FROM AUTHOR]

Abstract The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P

Abstract Origanum vulgare has been of great interest in academia and pharma industry due to its antioxidant, antifungal and antitumor properties. The present study aimed to find the anti-MRSA potential and in vivo toxicity assessments of O. vulgare. O. vulgare extract was used to monitor anti-MRSA activity in mice. Following MRSA established infection in mice (Mus musculus), treatment with O. vulgare was continued for 7 days. Autopsies were performed and re-isolation, gross lesion scoring and bacterial load in various organs were measured. Additionally, blood sample was analysed for hematological assays. Toxicity assessment of O. vulgare potential as medicine was done at 200 mg/kg and 400 mg/kg by evaluating liver and kidney functions. Bacterial load and gross lesion in lungs and heart were significantly low compared to positive control following O. vulgare treatment. Likewise, O. vulgare treated groups had hematological, neutrophil and TLC values similar to control groups. Increased AST, ALP and total bilirubin alongwith marked hepatocellular degeneration and distortion around the central vein, inflammatory cell infiltration, and cytoplasmic vacuolization of hepatic cells was observed at higher dose. It is concluded that crude extract of O. vulgare may contain beneficial secondary metabolites and in future may be explored for curing infectious diseases.

Scientific evidence suggests that quercetin (QUR) has anxiolytic-like effects in experimental animals. However, the mechanism of action responsible for its anxiolytic-like effects is yet to be discovered. The goal of this research is to assess QUR’s anxiolytic effects in mouse models to explicate the possible mechanism of action. After acute intraperitoneal (i.p.) treatment with QUR at a dose of 50 mg/kg (i.p.), behavioral models of open-field, hole board, swing box, and light–dark tests were performed. QUR was combined with a GABAergic agonist (diazepam) and/or antagonist (flumazenil) group. Furthermore, in silico analysis was also conducted to observe the interaction of QUR and GABA (α5), GABA (β1), and GABA (β2) receptors. In the experimental animal model, QUR had an anxiolytic-like effect. QUR, when combined with diazepam (2 mg/kg, i.p.), drastically potentiated an anxiolytic effect of diazepam. QUR is a more highly competitive ligand for the benzodiazepine recognition site that can displace flumazenil (2.5 mg/kg, i.p.). In all the test models, QUR acted similar to diazepam, with enhanced effects of the standard anxiolytic drug, which were reversed by pre-treatment with flumazenil. QUR showed the best interaction with the GABA (α5) receptor compared to the GABA (β1) and GABA (β2) receptors. In conclusion, QUR may exert an anxiolytic-like effect on mice, probably through the GABA-receptor-interacting pathway.

Alzheimer’s disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (h1–h5) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light–dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues h2 and h3 with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (p < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically h2 and h3, significantly decreased (123.71 ± 15.23 s (p < 0.001), n = 8; 156.53 ± 14.13 s (p < 0.001), n = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (p < 0.001), n = 8, and 239.57 ± 9.98 s (p < 0.001), n = 8) the time spent in the dark compartment in the light–dark box arena. The numbers of hole pokings were significantly (p < 0.001, n = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models.

The glycaemic index (GI) is used to demonstrate the tendency of foods to increase blood glucose and is thus an important characteristic of newly formulated foods to tackle the rising prevalence of diabetics and associated diseases. The GI of gluten-free biscuits formulated with alternate flours, resistant starch and sucrose replacers was determined using in vivo methods with human subjects. The relationship between in vivo GI values and the predicted glycaemic index (pGI) from the in vitro digestibility-based protocols, generally used by researchers, was established. The in vivo data showed a gradual reduction in GI with increased levels of sucrose substitution by maltitol and inulin with biscuits where sucrose was fully replaced, showing the lowest GI of 33. The correlation between the GI and pGI was food formulation-dependent, even though GI values were lower than the reported pGI. Applying a correction factor to pGI tend to close the gap between the GI and pGI for some formulations but also causes an underestimation of GI for other samples. The results thus suggest that it may not be appropriate to use pGI data to classify food products according to their GI.

To evaluate the anticoccidial effect of the Hura crepitans seed, 21 cross-breed lambs, 23 ± 3 kg live weight (PV) and 70 ± 6 days old, were used. Animals were housed individually in raised wire-mesh pens, with individual water troughs and feeders. Lambs were randomly divided into three groups (n = 7) that received different doses of Hura crepitans seeds: 4 g/kg B.W. (group 1), 6 g/kg B.W. (group 2) and 0 g/kg B.W. (control group or group 0). The treatment was administered at the beginning of the experiment once orally and the study lasted 21 days. Stool samples were taken for quantitative analysis of oocysts using the McMaster technique and blood for haematological and biochemical analysis. Lambs that received the seeds showed a higher excretion of coccidia oocysts between days 5 and 7 after treatment (p < 0.05) due to the antiparasitic effect of these seeds, without affecting their productive performance (daily feed intake (DFI)- total weight gain (TWG), daily weight gain (DWG)). In addition, the daily feed consumption (DFC) and dry matter intake (DMI) were similar between the groups. The analysed enzymes (ALT, AST, GGT and FA) and creatinine showed reference values. Only the urea and BUN levels were slightly increased, but without statistical difference between the groups. Therefore, the Hura crepitans seed, at doses of 4 and 6 g/kg, favours the expulsion of coccidial oocysts, without affecting either the health or the productive behaviour of lambs.

The aim of this study is to evaluate the wear volume of interim crowns fabricated using digital light processing 3D printing according to the printing angle. A total of five patients undergoing the placement of a single crown on the mandibular molar were included. Interim crowns were fabricated directly in the oral cavity using the conventional method. A digital light processing 3D printer was then used to fabricate crowns with build angles of 0, 45, and 90 degrees. Therefore, four fabricated interim crowns were randomly delivered to the patients, and each was used for one week. Before and after use, the intaglio surfaces of the interim crowns were scanned using a 3D scanner. The volume changes before and after use were measured, and changes in the height of the occlusal surface were evaluated using the root mean square value. Data normality was verified by statistical analysis, and the wear volume in each group was evaluated using a one-way analysis of variance and Tukey’s honestly significant difference test (α = 0.05). Compared with the RMS values of the conventional method (11.88 ± 2.69 µm) and the 3D-printing method at 0 degrees (12.14 ± 2.38 µm), the RMS values were significantly high at 90 degrees (16.46 ± 2.39 µm) (p < 0.05). Likewise, there was a significant difference in the change in volume between the groups (p = 0.002), with a significantly higher volume change value at 90 degrees (1.74 ± 0.41 mm3) than in the conventional method (0.70 ± 0.15 mm3) (p < 0.05). A printing angle of 90 degrees is not recommended when interim crowns are fabricated using digital light processing 3D printing.

The purpose of this study was to evaluate muscle activation and fatigue in the operator during tooth preparation and intraoral scanning by simulating these tasks in two types of dental unit chair systems (UCS). Six participants were recruited, and the above tasks were simulated. Electrodes were placed on the skin over five types of muscles (arm, neck, and shoulder muscles), and the maximal voluntary contraction (MVC) was measured. Electromyography (EMG) was assessed during the simulation, and EMG values were normalized using MVC. The root mean square (RMS) EMG (%MVC) and muscle fatigue (%) were calculated. Owing to a lack of normal distribution of the data, Mann–Whitney U test and Kruskal–Wallis H test were performed for statistical comparison, and Bonferroni adjustment was performed for multiple comparisons (α = 0.05). There was no significant difference in RMS EMG between the two types of dental UCS (intraoral scanning, p = 0.237; tooth preparation, p = 0.543). Moreover, the RMS EMG and muscle fatigue were not significantly different between the two tasks (p > 0.05). There was significant muscle fatigue after the intraoral scanner use was simulated thrice (p < 0.001). It is necessary to refrain from performing continuous intraoral scanning and tooth preparation and to take appropriate rest to reduce the incidence of musculoskeletal disorders in dentists in clinical settings.

Antioxidants from natural sources are extensively attaining consideration to avert the skin from damage and aging caused by free radicals. Flaxseed (Linum usitatissimum L.), a natural therapeutic agent, was meant to be explored cosmeceutical by quantifying its potential phytoconstituents and to be incorporated into a microemulgel for topical use. Hydroalcoholic fractions (both methanolic and ethanolic; 80%) flaxseed extracts were subjected to phytochemical screening by quantifying total phenolic content (TPC), total flavonoid content (TFC), and high-performance liquid chromatography-ultraviolet (HPLC-UV), and for biological activities through 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, tyrosinase inhibition assay, and sun protection factor (SPF). Ethanolic fraction was selected for further study by TPC (18.75 mg gallic acid equivalent/g) and TFC (1.34 mg quercetin equivalent/g). HPLC-UV analysis showed the existence of benzoic, quercetin, caffeic, vanillic, p-coumaric, gallic, cinnamic, syringic, and sinapic acids. Biological activities showed 87.00%, 72.00%, and 21.75 values for DPPH assay, tyrosinase inhibition, and SPF assays, respectively. An oil-in-water (OW) microemulsion containing the flaxseed extract, with 99.20 nm Zeta size, −19.3 Zeta potential and 0.434 polydispersity index was developed and incorporated in Carbopol-940 gel matrix to formulate an active microemulgel with 59.15% release in in vitro studies. The successfully formulated stable active microemulgel produced statistically significant effects (p < 0.05), in comparison to a placebo, on skin erythema, melanin, sebum, moisture, and elasticity, in a noninvasive in vivo study performed on 13 healthy human female volunteers. Other cosmeceutical products can also be formulated from flaxseed, making it a considerable candidate for further utilization in the pharmaceutical industry.