Zoledronic acid (ZA) is often prescribed for osteoporosis or resorptive metabolic bone disease. This study aims to evaluate the effect of ZA on orthodontic tooth movement (OTM) and root and bone ...resorption and its repercussion on root, periodontal ligament and alveolar bone tissues. The experimental group consisted of 72 Wistar rats divided in four subgroups: Naive, Saline and Zoledronic Acid groups at the concentration of 0.2 mg/kg ZA (0.2) or 1.0 mg/kg ZA (1.0). The animals were subjected to i.v (dorsal penile vein) administrations of ZA or saline solution, on days 0, 7, 14 and 42. Under anesthesia, NiTi springs were installed in the first left maxillary molar with 50gf allowing the OTM, except for the negative control group (N) for mesial movement of the left first maxillary teeth. The animals were sacrificed and maxillae were removed for macroscopic and histopathological analyzes, scanning electron microscopy, computerized microtomography and confocal microscopy. Treatment with ZA decreased the OTM and the number of osteoclasts and loss of alveolar bone when compared to the naive and saline groups. Reduction of radicular resorption, increased necrotic areas and reduced vascularization in the periodontal ligament were observed in the ZA groups. ZA interferes with OTM and presents anti-resorptive effects on bone and dental tissues associated with a decreased vascularization, without osteonecrosis.
, the main cause of diarrhea in hospitalized patients, produces toxins A (TcdA) and B (TcdB), which affect intestinal epithelial cell survival, proliferation, and migration and induce an intense ...inflammatory response. Transforming growth factor β (TGF-β) is a pleiotropic cytokine affecting enterocyte and immune/inflammatory responses. However, it has been shown that exposure of intestinal epithelium to a low concentration of TcdA induces the release of TGF-β1, which has a protective effect on epithelial resistance and a TcdA/TGF-β signaling pathway interaction. The activation of this pathway
has not been elucidated. The aim of this study was to investigate the role of the TGF-β1 pathway in TcdA-induced damage in a rat intestinal epithelial cell line (IEC-6) and in a mouse model of an ileal loop. TcdA increased the expression of TGF-β1 and its receptor, TβRII,
and
TcdA induced nuclear translocation of the transcription factors SMAD2/3, a hallmark of TGF-β1 pathway activation, both in IEC cells and in mouse ileal tissue. The addition of recombinant TGF-β1 (rTGF-β) prevented TcdA-induced apoptosis/necrosis and restored proliferation and repair activity in IEC-6 cells in the presence of TcdA. Together, these data show that TcdA induces TGF-β1 signaling pathway activation and suggest that this pathway might play a protective role against the effect of
-toxin.
A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 ...(AT1) and Ang II type 2 (AT2) receptors on periodontitis.
Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR.
The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (
< 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L.
Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.
This study aimed to evaluate whether NIRS-derived reperfusion rate would detect potential differences in the forearm microvascular responsiveness between young healthy adults, and older adults free ...from or with cardiovascular disease (CVD) risk factors. Fifteen healthy young (age: 24.8 ± 4.0 years), seventeen older adults free of CVD risk factors (age: 67.0 ± 6.8 years), and twenty-three older adults with CVD risk factors (age: 67.9 ± 8.0 years) participated this study. Individuals underwent a blood draw and vascular occlusion test (30 s of baseline, 5 min of occlusion, and 2 min of reperfusion) and microvascular responsiveness was evaluated by using NIRS-derived tissue oxygen saturation indexes during reperfusion. A significant slower reperfusion rate and lower reperfusion magnitude was observed in older adults with CVD risk factors compared to healthy young and older adults. Although no statistical differences were found between healthy young and older individuals, there was a small (d = 0.4) effect size for reperfusion rate and moderate (d = 0.7) effects size for reperfusion magnitude when comparing these groups. In conclusion, this study demonstrated that even though the effects of aging per se on microvascular function should not be completely neglected, the CVD risk factors seem to be determinant on microvascular responsiveness impairment associated with aging.
•The effect of the aging and cardiovascular risk factors on vascular function•Cardiovascular risk factors associated with aging impair microvascular responsiveness.•The effect of the aging on microvascular responsiveness should not be neglected.
Objective
This work aimed to study the role of inflammation in medication-related osteonecrosis of the jaw (MRONJ) in rats with focus on Wnt signaling.
Methods
A total of 36 female Wistar rats ...(12 weeks ± 200 g) were divided into 2 groups (
n
= 6) in 3 experiments: saline (SAL) and zoledronic acid (ZOL). For MRONJ induction, rats received 0.1 mg/kg of ZOL (ip) 3×/week for 9 weeks. Animals from the SAL group received 0.1 mg/kg of 0.9% SAL, ip 3×/week for 9 weeks. On the 8th week, 3 left upper molars were extracted, and on the 11th week, they were euthanized. Maxillae were evaluated by macroscopic and histopathological analyses; scanning electron microscopy (SEM); immunohistochemistry for DKK-1, Wnt 10b, and caspase-3; and Raman spectrometry. Gingiva was also collected for TNF-α e IL-1β quantification.
Results
Bone necrosis was confirmed by healing impairment, reduced number of viable osteocytes, increased caspase-3 immunoexpression, and increased number of empty lacunae (
p
< 0.05). ZOL enhanced inflammation and increased gingival levels of IL-1β and TNF-α (
p
< 0.05). Irregular indentations were seen on bone after ZOL administration. Bone necrosis was marked by reduced amount of total and type I collagen. ZOL reduced the mineral/matrix ratio and increased carbonate/phosphate ratio. It was observed a significant reduction on Wnt10b and beta-catenin immunolabeling in the bone tissue of ZOL group.
Conclusion
In summary, MRONJ model caused bone necrosis due to intense inflammation. Wnt signaling seems to play an important role in this process.
Clinical relevance
New therapeutic strategies focusing on Wnt pathway can provide an interesting approach for future treatments.
Purpose
This study aimed to investigate the effects of AGE on microvascular reactivity, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in older individuals at high risk for ...cardiovascular disease (CVD). Urinary thiosulfate was also investigated as an indirect marker of endogenous hydrogen sulfide (H
2
S) synthesis. The study was conducted in a randomized, double-blind, crossover, and placebo-controlled way.
Methods
Twenty-eight participants (14 male), 67 ± 6 years old with CVD risk factors, ingested 2.4 g of AGE or placebo (PLA). Near-infrared spectroscopy evaluated tissue oxygen saturation (StO
2
) during a vascular occlusion test (30 s baseline, 5 min occlusion, and 2 min reperfusion). The upslope of StO
2
signal after cuff release was calculated to measure microvascular reactivity. Urinary thiosulfate levels were measured using a high-performance liquid chromatography system.
Results
The upslope of StO
2
was significantly faster after AGE (1.01 ± 0.37% s
−1
) intake compared to PLA (0.83 ± 0.35% s
−1
;
P
< 0.001;
d
= 0.50). Relative changes in Δ% SBP from pre- to post-AGE intake (− 5.17 ± 5.77%) was significantly different compared to Δ% PLA (0.32 ± 5.99%;
P
= 0.001;
d
= 0.93). No significant changes in urinary thiosulfate concentrations were observed between interventions. Moreover, no significant gender effect in any parameter assessed was found.
Conclusion
This study demonstrated that a single dose of AGE improved microvascular reactivity in older adults at risk of CVD despite such an effect was not linked with urinary thiosulfate levels. This trial was registered at clinicaltrials.gov as NCT04008693 (May 19, 2020).
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This study aimed to elucidate the anti-inflammatory, anti-oxidant and antifibrotic effects of gold nanoparticles (GNPs) in rats subjected to liver injury with ethanol and ...Methamphetamine (METH). The liver injury was induced by gavage administrations of 30% alcoholic solution (7 g/kg) once a day during 28 days, followed by METH (10 mg/kg) on the 20th and 28th days of treatment. GNPs treatment (724.96 µg/kg) during the ethanol and METH exposure was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis. Furthermore, there was a reduction in biochemical markers of liver damage and oxidative stress, and pro-inflammatory cytokines IL-1β and TNF-α, compared to ethanol + METH group alone. A decrease of FGF, SOD-1 and GPx-1 expression was also observed. GNPs down-regulated the activity of Kupffer cells and hepatic stellate cells affecting the profile of their pro-inflammatory cytokines, oxidative stress and fibrosis through modulation of signaling pathways AKT/PI3K and MAPK in ethanol + METH-induced liver injury in a rat model.
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This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established ...oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1β), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition.
Vascular occlusion test (VOT)-induced reactive hyperemia in brachial artery is crucial to flow-mediated dilation (FMD). Emerging studies have suggested that reactive hyperemia depends on the ...magnitude of the O
desaturation (ischemia) in downstream microvessels. Although near-infrared spectroscopy-derived tissue O
saturation index (TSI) has been used to assess the magnitude of ischemia, the association between FMD and the magnitude of O
desaturation has not been addressed. Therefore, the aim of the present study was to evaluate whether FMD correlates with the magnitude of muscle O
desaturation in healthy young individuals and older adults at risk for cardiovascular disease (CVD). Twenty healthy young individuals and 20 others at risk for CVD participated in the study. The magnitude of ischemic stimulus was determined by calculating the area under curve of TSI signal over 5 min of cuff occlusion period. Oxygen resaturation rate was calculated as the upslope of the TSI signal over 10 s following cuff deflation. There was no significant correlation between FMD and the magnitude of ischemic stimulus in both groups assessed (young: R = 0.327; P = 0.159 and older: R = -0.184; P = 0.436). However, a significant correlation between the magnitude of O
desaturation and O
resaturation rate in young (R = 0.555; P = 0.011) and older individuals at risk for CVD (R = 0.539; P = 0.014). In conclusion, FMD response did not correlate with the magnitude of muscle O
desaturation, although it seems to be partially associated with O
resaturation rate.
The development of new biomaterials based on natural products for wound treatment is a frequent research topic in recent years. In this study, the hydroalcoholic extract from Agaricus blazei Murill ...(EAb) was incorporated in microgels based on poly (vinyl alcohol) (PVA) and sodium alginate (SA). Microgels were characterized according to their physicochemical and morphological properties. An in vivo wound healing assay was performed and histomorphometric parameters and oxidative stress were studied. The physicochemical characterizations showed the occurrence of intermolecular interactions between both polymers and this natural product, suggesting a potential physical cross-linking. The microgels presented sol-gel transition (G’ > G’’) at low frequencies, porosity degree around 40 % and significant ability to scavenge the DPPH radical. Morphological characterization evidenced pores on the micrometric scale, where EAb granules (0.3–0.6 µm) are trapped. On the 14th day, mice treated with EAb-loaded microgels presented wound contraction > 99 %, as well as greater epidermis and dermis thickness, higher density of type I collagen and significant reduction in oxidative stress. Our results showed that EAb-loaded microgels, especially the M0.5 formulation, are a promising multifunctional biomaterial for wound dressing applications.
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