Artigos - Fisiologia e Patologia - FOAR

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Inhibition of salty taste and sodium appetite by estrogens in spontaneously hypertensive rats
(2023-01-01) Pereira, Emilson Donizete [UNESP]; Zenatti, Aline Aparecida [UNESP]; Menani, José Vanderlei [UNESP]; De Luca, Laurival Antonio [UNESP]; Andrade, Carina A. F. [UNESP]; Universidade Estadual Paulista (UNESP)
Estrogen has a well-known effect of reducing salt intake in rats. This mini review focuses on recent findings regarding the interaction of estradiol with brain angiotensin II to control increased sodium palatability that occurs as a result of sodium appetite in spontaneously hypertensive rats.
Effects of red and infrared laser on post extraction socket repair in rats subjected to alendronate therapy
(2023-01-01) Gonçalves, Fernanda Castanheira [UNESP]; Mascaro, Bruno Arruda [UNESP]; Oliveira, Guilherme José Pimentel Lopes de; Spolidório, Luis Carlos [UNESP]; Marcantonio, Rosemary Adriana Chiérici [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Federal de Uberlândia (UFU)
This study evaluated the effect of photobiomodulation therapy (PBMT) with a red or infrared laser on the repair of post extraction sockets in rats administered alendronate (ALN). Forty male rats were randomly allocated into four groups: Control Group (CTR): subcutaneous administration of saline solution throughout the experimental period; Alendronate Group (ALN): subcutaneous administration of alendronate during the entire experimental period; Alendronate/Red Laser Group (ALN/RL): administration of ALN and irradiation with a GaAlAs laser (λ 660 nm); and Alendronate/Infrared Laser Group (ALN/IRL): administration of ALN and irradiation with a GaAlAs laser (λ 830 nm). The first lower molars were extracted 60 days after the beginning of the administration of the drugs. The PBMT was applied after tooth extraction (7 sessions with intervals of 48 hours between sessions). Thirty days after tooth extraction, the animals were euthanized. Micro-CT and histometric analysis were performed to assess the bone healing and soft tissue repair of the tooth socket. The ALN group presented with more bone than the CTR; however, most of this bone was necrotic. ALN does not affect the bone microarchitecture. On the other hand, PBMT with IRL enhances the bone density due to the increase in the number and reduction in the spacing of the trabeculae. The amount of vital bone and connective tissue matrix was higher in the ALN/RL and ALN/IRL groups than in the ALN and CTR groups. PBMT enhanced the healing of the post extraction sockets in rats subjected to ALN administration. Furthermore, IRL improved the new bone microarchitecture.
Post-partum depression: From clinical understanding to preclinical assessments
(2023-01-01) Moreira, Lorrane K. S.; Moreira, Caroline V. L.; Custódio, Carlos H. X.; Dias, Matheus L. P.; Rosa, Daniel A.; Ferreira-Neto, Marcos L.; Colombari, Eduardo [UNESP]; Costa, Elson A.; Fajemiroye, James O.; Pedrino, Gustavo R.; Universidade Federal de Goiás (UFG); Universidade Federal de Uberlândia (UFU); Universidade Estadual Paulista (UNESP); Evangelical University of Goiás
Post-partum depression (PPD) with varying clinical manifestations affecting new parents remains underdiagnosed and poorly treated. This minireview revisits the pharmacotherapy, and relevant etiological basis, capable of advancing preclinical research frameworks. Maternal tasks accompanied by numerous behavioral readouts demand modeling different paradigms that reflect the complex and heterogenous nature of PPD. Hence, effective PPD-like characterization in animals towards the discovery of pharmacological intervention demands research that deepens our understanding of the roles of hormonal and non-hormonal components and mediators of this psychiatric disorder.
Palatability profile in spontaneously hypertensive rats
(2023-01-01) Pereira, Emilson Donizete [UNESP]; De Luca, Laurival A. [UNESP]; Menani, José Vanderlei [UNESP]; Andrade, Carina Aparecida Fabrício [UNESP]; Universidade Estadual Paulista (UNESP)
The spontaneously hypertensive rats (SHRs) have enhanced palatability for NaCl taste as measured by the increased number of hedonic versus aversive responses to intraoral infusion (1 mL/1 min) of 0.3 M NaCl, in a taste reactivity test in euhydrated condition or after 24 h of water deprivation + 2 h of partial rehydration (WD-PR). SHRs also ingested more sucrose than normotensive rats, without differences in quinine hydrochloride intake. Here, we investigated the palatability of SHRs (n = 8–10) and normotensive Holtzman rats (n = 8–10) to sucrose and quinine sulphate infused intraorally in the same conditions that NaCl palatability was increased in SHRs. SHRs had similar number of hedonic responses to 2% sucrose in euhydrated condition (95 ± 19) or after WD-PR (142 ± 25), responses increased when compared with normotensive rats in euhydrated condition (13 ± 3) or after WD-PR (21 ± 6). SHRs also showed increased number of aversive responses to 1.4 mM quinine sulphate compared with normotensive rats, whether in euhydrated condition (86 ± 6, vs. normotensive: 54 ± 7) or after WD-PR (89 ± 9, vs. normotensive: 40 ± 9). The results suggest that similar to NaCl taste, sweet taste responses are increased in SHRs and resistant to challenges in bodily fluid balance. They also showed a more intense aversive response in SHRs to bitter taste compared with normotensives. This suggests that the enhanced response of SHRs to taste rewards does not correspond to a decreased response to a typical aversive taste.
Chronic administration of catalase inhibitor attenuates hypertension in renovascular hypertensive rats
(2023-04-15) Lauar, Mariana R. [UNESP]; Colombari, Débora S.A. [UNESP]; De Paula, Patrícia M. [UNESP]; Colombari, Eduardo [UNESP]; Andrade, Carina A.F. [UNESP]; De Luca, Laurival A. [UNESP]; Menani, José V. [UNESP]; Universidade Estadual Paulista (UNESP)
Aims: Reactive oxygen species like hydrogen peroxide (H2O2) are produced endogenously and may participate in intra- and extracellular signaling, including modulation of angiotensin II responses. In the present study, we investigated the effects of chronic subcutaneous (sc) administration of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ) on arterial pressure, autonomic modulation of arterial pressure, hypothalamic expression of AT1 receptors and neuroinflammatory markers and fluid balance in 2-kidney, 1clip (2K1C) renovascular hypertensive rats. Materials and methods: Male Holtzman rats with a clip occluding partially the left renal artery and chronic sc injections of ATZ were used. Key findings: Subcutaneous injections of ATZ (600 mg/kg of body weight/day) for 9 days in 2K1C rats reduced arterial pressure (137 ± 8, vs. saline: 182 ± 8 mmHg). ATZ also reduced the sympathetic modulation and enhanced the parasympathetic modulation of pulse interval, reducing the sympatho-vagal balance. Additionally, ATZ reduced mRNA expression for interleukins 6 and IL-1β, tumor necrosis factor-α, AT1 receptor (0.77 ± 0.06, vs. saline: 1.47 ± 0.26 fold change), NOX 2 (0.85 ± 0.13, vs. saline: 1.75 ± 0.15 fold change) and the marker of microglial activation, CD 11 (0.47 ± 0.07, vs. saline, 1.34 ± 0.15 fold change) in the hypothalamus of 2K1C rats. Daily water and food intake and renal excretion were only slightly modified by ATZ. Significance: The results suggest that the increase of endogenous H2O2 availability with chronic treatment with ATZ had an anti-hypertensive effect in 2K1C hypertensive rats. This effect depends on decreased activity of sympathetic pressor mechanisms and mRNA expression of AT1 receptors and neuroinflammatory markers possibly due to reduced angiotensin II action.
Testosterone replacement relieves ligature-induced periodontitis by mitigating inflammation, increasing pro-resolving markers and promoting angiogenesis in rats: A preclinical study
(2023-02-01) Pelegrin, Álvaro Formoso [UNESP]; de Paiva Gonçalves, Vinícius; Carvalho, Jhonatan de Souza [UNESP]; Spolidorio, Denise Madalena Palomari [UNESP]; Spolidorio, Luís Carlos [UNESP]; Universidade Estadual Paulista (UNESP); Pontifical Catholic University of Minas Gerais
Objectives: This study aimed to evaluate the inflammatory profile as well as the resolution of inflammation in a ligature-induced periodontal inflammation in rats with depletion and/or supraphysiological testosterone replacement. Design: Sixty male rats (Holtzman) were used in the present study. Study groups were created as following: (1) Sham (no testicle removal); (2) Orchiectomy (OCX), 3) OCX + Testosterone (OCX + T); (4) Sham + Ligature (SH + L); (5) OCX+L; and 6) OCX + T + L. The surgeries were performed on day 1, and testosterone was administered weekly since day 1. On day 15, a cotton ligature was placed around the lower first molars and maintained for 15 days. Morphological changes in periodontal tissues were determined by histopathological analysis. Immunohistochemistry (factor VIII) and immunoenzymatic assay were performed to evaluate angiogenesis process and (pro- and anti-) inflammatory markers, respectively. Results: Ligature promoted a marked inflammatory gingival infiltrate and bone loss (P < 0.05). Supraphysiological testosterone treatment increased the percentage of blood vessels, extracellular matrix and fibroblasts in the presence and absence of periodontal inflammation (P < 0.05). A high dose of testosterone increased factor VIII+ blood vessels and IL-10 expression in inflamed gingival tissue, while PGE2, LXA4 and MPO were reduced as a result of supraphysiological testosterone administration (P < 0.05). Conclusions: These results, in our experimental model, suggest that supraphysiological testosterone treatment stimulated gingival tissue repair during ligature-induced periodontitis, and it seems to be related to an anti-inflammatory and pro-resolutive mechanism resulting by the modulatory effect on PGE2 and IL-10 related to an enhanced angiogenesis.
Participation of the angiotensinergic and vasopressinergic mechanisms in the maintenance of cardiorespiratory parameters in sodium depleted rats
(2022-12-01) Cardoso, Fernanda [UNESP]; Fávero, Michele Thaís [UNESP]; Veríssimo, Nathalia Vieira [UNESP]; Furtado Menezes, Miguel [UNESP]; Menani, José Vanderlei [UNESP]; de Paula, Patricia Maria [UNESP]; Universidade Estadual Paulista (UNESP)
Changes in blood volume can be caused by different conditions, such as vomiting, diarrhea, alteration of sodium intake, trauma, or the use of diuretics, which can lead to severe health deterioration. Understanding the mechanisms involved in the maintenance of physiological parameters and the hydroelectrolytic balance of the human body during hypovolemia, can help with preventing and handling these high-risk situations. Hence, this study investigated cardiorespiratory [mean arterial pressure (MAP), heart rate (HR), pulmonary ventilation (VE)] and blood parameters, of sodium depleted rats with furosemide and the roles of the central and peripheral renin-angiotensin and the peripheral vasopressinergic systems in controlling blood pressure in these animals. Different groups under the same conditions received subcutaneous (s.c.) injections of furosemide (diuretic/saliuretic) or vehicle, intracerebroventricular (i.c.v.) or intravenous (i.v.) injections of losartan [angiotensin II (ANG II) AT1 receptor antagonist] or saline, and i.v. injections of Manning compound (AVPX, vasopressin V1 receptor antagonist). Sodium depletion increased the VE (708 ± 71, vs. normovolemic: 478 ± 40 mL/min/kg body wt) and did not modify baseline mean arterial pressure (104 ± 4, vs. normovolemic: 105 ± 4 mmHg) and heart rate (334 ± 20, vs. normovolemic: 379 ± 13 bpm). The i.v. losartan (10 mg/kg of body wt) treatment significantly reduced MAP in all groups and elevated HR, with a greater impact in sodium depleted rats before repletion. On the other hand, the i.c.v. losartan (3.3 μg/kg of body wt) and i.v. AVPX (10 μg/kg of body wt) treatments did not alter the MAP and HR in control, sodium depleted, and sodium repleted rats. These results indicate that sodium depletion affects cardiorespiratory control increasing baseline ventilation and peripheral angiotensinergic mechanisms are relevant for maintaining cardiovascular parameters in sodium depleted rats. Besides, this study suggests vasopressin V1 receptors do not participate in the maintenance of MAP and HR in sodium depleted animals with furosemide.
Biosynthesis of silver nanoparticles from Syzygium cumini leaves and their potential effects on odontogenic pathogens and biofilms
(2022-09-29) Bernardo, Wagner Luis de Carvalho [UNESP]; Boriollo, Marcelo Fabiano Gomes; Tonon, Caroline Coradi [UNESP]; da Silva, Jeferson Júnior; Oliveira, Mateus Cardoso; de Moraes, Fernando Cruz; Spolidorio, Denise Madalena Palomari [UNESP]; Universidade Estadual Paulista (UNESP); Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Carlos (UFSCar)
This study analyzed the antimicrobial and antibiofilm action and cytotoxicity of extract (HEScL) and silver nanoparticles (AgNPs-HEScL) from Syzygium cumini leaves. GC–MS, UV–Vis, EDX, FEG/SEM, DLS and zeta potential assays were used to characterize the extract or nanoparticles. Antimicrobial, antibiofilm and cytotoxicity analyses were carried out by in vitro methods: agar diffusion, microdilution and normal oral keratinocytes spontaneously immortalized (NOK-SI) cell culture. MICs of planktonic cells ranged from 31.2–250 (AgNPs-HEScL) to 1,296.8–10,375 μg/ml (HEScL) for Actinomyces naeslundii, Fusobacterium nucleatum, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Streptococcus oralis, Veillonella dispar, and Candida albicans. AgNPs-HEScL showed antibiofilm effects (125–8,000 μg/ml) toward Candida albicans, Streptococcus mutans and Streptococcus oralis, and Staphylococcus aureus and Staphylococcus epidermidis. The NOK-SI exhibited no cytotoxicity when treated with 32.8 and 680.3 μg/ml of AgNPs-HEScL and HEScL, respectively, for 5 min. The data suggest potential antimicrobial and antibiofilm action of HEScL, and more specifically, AgNPs-HEScL, involving pathogens of medical and dental interest (dose-, time- and species-dependent). The cytotoxicity of HEScL and AgNPs-HEScL detected in NOK-SI was dose- and time-dependent. This study presents toxicological information about the lyophilized ethanolic extract of S. cumini leaves, including their metallic nanoparticles, and adds scientific values to incipient studies found in the literature.
A new approach for professional dental bleaching using a polymeric catalyst primer
(2023-03-01) Dias, Marlon Ferreira [UNESP]; Martins, Beatriz Voss [UNESP]; de Oliveira Ribeiro, Rafael Antonio [UNESP]; Leite, Maria Luísa [UNESP]; Ortecho-Zuta, Uxua [UNESP]; Hebling, Josimeri [UNESP]; Costa, Carlos Alberto de Souza [UNESP]; Universidade Estadual Paulista (UNESP)
Objective: Evaluate the influence of a polymeric catalyst primer (PCP) on esthetic efficacy (EE), degradation kinetics of hydrogen peroxide (H2O2), and trans-amelodentinal cytotoxicity (TC) of bleaching gels. Materials and Methods: The following groups were established: G1: No treatment (NC, negative control); G2: PCP; G3: 10% H2O2; G4: PCP + 10% H2O2; G5: 20% H2O2; G6: PCP + 20% H2O2; G7: 35% H2O2 (positive control); G8: PCP + 35% H2O2. To determine EE, enamel/dentin discs (E/DDs) were stained and subjected or not to bleaching protocols for 45 min. To assess TC, the E/DDs were adapted to artificial pulp chambers. The extracts (culture medium + gel components diffused through E/DDs) were applied to odontoblast-like MDPC-23 cells. The viability (VB), oxidative stress (OxS), morphology (SEM), amount of H2O2 diffused and the production of hydroxyl radical (OH•) were assessed (two-way ANOVA/Tukey/paired Student t-test; p < 0.05). Results: The highest EE was found in G8 (p < 0.05), and G4, G6, and G7 did not differ statistically (p > 0.05). In G4, the limited H2O2 diffusion reduced OxS and increased cell VB (p < 0.05). Conclusions: Coating the enamel with PCP containing 10 mg/ml of manganese oxide before applying the 10% H2O2 bleaching gel maintains the EE of conventional in-office bleaching and minimizes the toxic effects of this esthetic therapy. Clinical Significance: Coating the enamel with a PCP before applying the bleaching gel may potentiate the EE of the conventional in-office tooth bleaching and reduce the toxicity of this professional therapy to the dental pulp.
EGF coating of titanium surfaces modulates cytokines in oral mucosal primary cells exposed to TNF-α
(2023-01-01) Pansani, Taisa Nogueira [UNESP]; Basso, Fernanda Gonçalves; Cardoso, Laís Medeiros [UNESP]; de Souza Costa, Carlos Alberto [UNESP]; Universidade Estadual Paulista (UNESP); UNAERP
Objective: This study assessed the metabolism of oral mucosal cells cultured on titanium discs (Ti) coated (or not) with epidermal growth factor (EGF) and exposed to tumor necrosis factor alpha (TNF-α). Methods: Fibroblasts or keratinocytes were seeded on Ti coated or not with EGF, and then exposed to 100 ng/mL of TNF-α for 24 h. Groups were established: G1: Ti (control); G2: Ti + TNF-α; G3: Ti + EGF; and G4: Ti + EGF + TNF-α. Both cell lines were evaluated for: viability (AlamarBlue®, n = 8); interleukin 6 and 8 (IL-6, IL-8) gene expression (qPCR, n = 5), and protein synthesis (ELISA, n = 6). For keratinocytes cells, the matrix metalloproteinase type 3 (MMP-3) was evaluated by qPCR (n = 5) and ELISA (n = 6). A 3-D culture of fibroblasts was analyzed by confocal microscopy. The data were subjected to ANOVA analysis, α = 5%. Results: Increased cell viability was observed in all groups compared with G1. Enhanced gene expression and synthesis of IL-6 and IL-8 by fibroblasts and keratinocytes in G2 and modulation of hIL-6 gene expression in G4 was noted. Modulation of IL-8 synthesis occurred in keratinocytes in G3 and G4. Keratinocytes in G2 showed enhanced gene expression of hMMP-3. A 3-D culture showed more cells in G3. Fibroblasts in G2 exhibited disrupted cytoplasmic membrane. Cells in G4 showed elongated morphology with intact cytoplasm. Conclusions: EGF coating increases cell viability and modulates the response of oral cells exposed to an inflammatory stimulus.
Cardiorespiratory interactions in health and disease
(2022-01-01) Zoccal, Daniel B. [UNESP]; Machado, Benedito H.; Moraes, Davi J.A.; Universidade Estadual Paulista (UNESP); Universidade de São Paulo (USP)
Like dancers in perfect synchrony, the cardiovascular and respiratory systems perform their functions in a coordinated way. Rhythmical oscillations in arterial pressure and heart rate follow inspiration and expiration, contributing to optimizing tissue perfusion and gas exchange processes and supporting the emergence of appropriate cardiorespiratory responses in conditions of elevated metabolic demand. The cardiorespiratory interaction begins at the central nervous system level. The brainstem neurons responsible for breathing generation communicate with neurons that control sympathetic and parasympathetic activities, modulating their firing frequency. Changes in the strength and pattern of respiratory-autonomic interactions have been reported in experimental models of cardiovascular diseases, identifying the respiratory modulation of the cardiovascular function as a relevant therapeutical strategy to be considered in cardiovascular diseases.
Effects of exposure to sediment-associated fipronil on cardiac function of Neotropical armored catfish Hypostomus regani
(2023-01-01) Ferro, Lucas Abreu [UNESP]; Fernandes, Suzana Luisa Alves [UNESP]; Kalinin, Ana Lúcia; Monteiro, Diana Amaral; Universidade Estadual Paulista (UNESP); Universidade Federal de São Carlos (UFSCar)
Fipronil is widely used as a broad-spectrum insecticide in agriculture, urban environments, and veterinary medicine. Fipronil can enter aquatic ecosystems and spread to sediment and organic matter, representing a risk to non-target species. This study aimed to evaluate the effects of short-term (96 h) exposure to a low and realistic concentration of sediment-associated fipronil (4.2 µg.kg−1 of Regent® 800 WG) on myocardial contractility of armored catfish Hypostomus regain, a benthic fish species. Fipronil exposure induced increased inotropism and acceleration of contractile kinetics, although no alterations in the relative ventricular mass were observed. This better cardiac function was associated with an elevated expression and/or function of the Na+/Ca2+ exchanger and its marked contribution to contraction and relaxation, probably due to a stress-induced adrenergic stimulation. Ventricle strips of exposed fish also exhibited a faster relaxation and a higher cardiac pumping capacity, indicating that armored catfish were able to perform cardiac adjustments to face the exposure. However, a high energetic cost to maintain an increased cardiac performance can make fish more susceptible to other stressors, impairing developmental processes and/or survival. These findings highlight the need for regulations of emerging contaminants, such as fipronil, to ensure adequate protection of the aquatic system.
Assessment of the regenerative potential of macro-porous chitosan-calcium simvastatin scaffolds on bone cells
(2023-01-01) De Oliveira Gallinari, Marjorie; Bordini, Ester Alves Ferreira; De Toledo Stuani, Vitor; Cassiano, Fernanda Balestrero; De Melo, Camila Correa Da Silva Braga; De Almeida, Juliano Milanezi [UNESP]; Cintra, Luciano Tavares Ângelo [UNESP]; De Souza Costa, Carlos Alberto [UNESP]; Soares, Diana Gabriela; Universidade de São Paulo (USP); Universidade Estadual Paulista (UNESP)
This study evaluated the bioactive potential of a macro-porous chitosan scaffold incorporated with calcium hydroxide (CH-Ca) and functionalized with bioactive doses of simvastatin (SV) for bone tissue regeneration. Initially, the bioactive dose of SV in osteoblastic cells (SAOS-2) was determined. For the direct contact experiment, SAOS-2 cells were plated on scaffolds to assess cell viability and osteogenic differentiation. The second assay was performed at a distance using extracts from scaffolds incubated in culture medium to assess the effect of conditioned medium on viability and osteogenic differentiation. The initial screening showed that 1 μM SV presented the best biostimulating effects, and this dose was selected for incorporation into the CH-Ca and pure chitosan (CH) scaffolds. The cells remained viable throughout the direct contact experiment, with the greatest cell density in the CH-Ca and CH-Ca-SV scaffolds because of their higher porosity. The CH-Ca-SV scaffold showed the most intense bio-stimulating effect in assays in the presence and absence of osteogenic medium, leading to an increased deposition of mineralized matrix. There was an increase in the viability of cells exposed to the extracts for CH-Ca, CH-SV, and CH-Ca-SV during the one-day period. There was an increase in ALP activity in the CH-Ca and CH-Ca-SV; however, the CH-Ca-SV scaffold resulted in an intense increase in the deposition of mineralized nodules, approximately 56.4% at 7 days and 117% at 14 days, compared with CH (control). In conclusion, functionalization of the CH-Ca scaffold with SV promoted an increase in bioactivity, presenting a promising option for bone tissue regeneration
SARS-CoV-2 and Hypertension: Evidence Supporting Invasion into the Brain Via Baroreflex Circuitry and the Role of Imbalanced Renin-Angiotensin-Aldosterone-System
(2023-01-01) Oliveira, Kellysson Bruno; Melo, Igor Santana de; Silva, Bianca Rodrigues Melo da; Oliveira, Keylla Lavínia da Silva; Sabino-Silva, Robinson; Anhezini, Lucas; Katayama, Pedro Lourenco [UNESP]; Santos, Victor Rodrigues; Shetty, Ashok K; Castro, Olagide Wagner de; Federal University of Alagoas (UFAL); Universidade Federal de Uberlândia (UFU); Federal University of Alagoas; Universidade Estadual Paulista (UNESP); Universidade Federal de Minas Gerais (UFMG); Texas AM University School of Medicine
Hypertension is considered one of the most critical risk factors for COVID-19. Evidence suggests that SARS-CoV-2 infection produces intense effects on the cardiovascular system by weakening the wall of large vessels via vasa-vasorum. In this commentary, we propose that SARS-CoV-2 invades carotid and aortic baroreceptors, leading to infection of the nucleus tractus solitari (NTS) and paraventricular hypothalamic nucleus (PVN), and such dysregulation of NTS and PVN following infection causes blood pressure alteration at the central level. We additionally explored the hypothesis that SARS-CoV-2 favors the internalization of membrane ACE2 receptors generating an imbalance of the renin-angiotensin-aldosterone system (RAAS), increasing the activity of angiotensin II (ANG-II), disintegrin, and metalloproteinase 17 domain (ADAM17/TACE), eventually modulating the integration of afferents reaching the NTS from baroreceptors and promoting increased blood pressure. These mechanisms are related to the increased sympathetic activity, which leads to transient or permanent hypertension associated with SARS-CoV-2 invasion, contributing to the high number of deaths by cardiovascular implications.
Molecular, Circuit, and Stress Response Characterization of Ventral Pallidum Npas1-Neurons
(2023-01-18) Morais-Silva, Gessynger [UNESP]; Campbell, Rianne R.; Nam, Hyungwoo; Basu, Mahashweta; Pagliusi, Marco; Fox, Megan E.; Chan, C. Savio; Iñiguez, Sergio D.; Ament, Seth; Cramer, Nathan; Marin, Marcelo Tadeu [UNESP]; Lobo, Mary Kay; School of Medicine; Universidade Estadual Paulista (UNESP); Universidade Estadual de Campinas (UNICAMP); Northwestern University; University of Texas at El Paso
Altered activity of the ventral pallidum (VP) underlies disrupted motivation in stress and drug exposure. The VP is a very heterogeneous structure composed of many neuron types with distinct physiological properties and projections. Neuronal PAS 1-positive (Npas11) VP neurons are thought to send projections to brain regions critical for motivational behavior. While Npas11 neurons have been characterized in the globus pallidus external, there is limited information on these neurons in the VP. To address this limitation, we evaluated the projection targets of the VP Npas11 neurons and performed RNA-sequencing on ribosome-associated mRNA from VP Npas11 neurons to determine their molecular identity. Finally, we used a chemogenetic approach to manipulate VP Npas11 neurons during social defeat stress (SDS) and behavioral tasks related to anxiety and motivation in Npas1-Cre mice. We used a similar approach in females using the chronic witness defeat stress (CWDS). We identified VP Npas11 projections to the nucleus accumbens, ventral tegmental area, medial and lateral habenula, lateral hypothalamus, thalamus, medial and lateral septum, and periaqueductal gray area. VP Npas11 neurons displayed distinct translatome representing distinct biological processes. Chemogenetic activation of hM3D(Gq) receptors in VP Npas11 neurons increased susceptibility to a subthreshold SDS and anxiety-like behavior in the elevated plus maze and open field while the activation of hM4D(Gi) receptors in VP Npas11 neurons enhanced resilience to chronic SDS and CWDS. Thus, the activity of VP Npas11 neurons modulates susceptibility to social stressors and anxiety-like behavior. Our studies provide new information on VP Npas11 neuron circuitry, molecular identity, and their role in stress response.
Calcium silicate-coated porous chitosan scaffold as a cell-free tissue engineering system for direct pulp capping
(2022-11-01) Leite, Maria Luísa; Anselmi, Caroline [UNESP]; Soares, Igor Paulino Mendes [UNESP]; Manso, Adriana Pigozzo; Hebling, Josimeri [UNESP]; Carvalho, Ricardo Marins; de Souza Costa, Carlos Alberto [UNESP]; The University of British Columbia; Universidade Estadual Paulista (UNESP)
Objectives: This study aimed to develop and characterize different formulations of porous chitosan scaffolds (SCH) associated with calcium silicate (CaSi) and evaluate their chemotactic and bioactive potential on human dental pulp cells (hDPCs). Methods: Different concentrations of CaSi suspensions (0.5%, 1.0%, and 2.0%, w/v) were incorporated (1:5; v/v) /or not, into 2% chitosan solution, giving rise to the following groups: SCH (control); SCH+ 0.5CaSi; SCH+ 1.0CaSi; SCH+ 2.0 CaSi. The resulting solutions were submitted to thermally induced phase separation followed by freeze-drying procedures to obtain porous scaffolds. The topography, pH, and calcium release kinetics of the scaffolds were assessed. Next, the study evaluated the influence of these scaffolds on cell migration (MG), viability (VB), proliferation (PL), adhesion and spreading (A&S), and on total protein synthesis (TP), alkaline phosphatase (ALP) activity, mineralized matrix deposition (MMD), and gene expression (GE) of odontogenic differentiation markers (ALP, DSPP, and DMP-1). The data were analyzed with ANOVA complemented with the Tukey post-hoc test (α = 5%). Results: Incorporation of the CaSi suspension into the chitosan scaffold formulation increased pore diameter when compared with control. Increased amounts of CaSi in the CH scaffold resulted in higher pH values and Ca release. In Groups SCH+ 1.0CaSi and SCH+ 2.0CaSi, increased VB, PF, A&S, GE of DSPP/DMP-1 and MMD values were shown. However, Group SCH+ 2.0CaSi was the only formulation capable of enhancing MG and showed the highest increase in TP, MMD, and GE of DMP-1 and DSPP values. Significance: SCH+ 2.0CaSi formulation had the highest chemotactic and bioactive potential on hDPCs and may be considered a potential biomaterial for pulp-dentin complex regeneration.
The influence of violet LED application time on the esthetic efficacy and cytotoxicity of a 35% H2O2 bleaching gel
(2022-12-01) Ribeiro, Rafael Antonio de Oliveira [UNESP]; Peruchi, Victória [UNESP]; Fernandes, Lídia de Oliveira [UNESP]; Anselmi, Caroline [UNESP]; Soares, Igor Paulino Mendes [UNESP]; Hebling, Josimeri [UNESP]; Costa, Carlos Alberto de Souza [UNESP]; Universidade Estadual Paulista (UNESP)
Objective: To assess the potential influence of violet LED (V-LED) application time on the esthetic efficacy and cytotoxicity of a 35% H2O2 bleaching gel. Methodology: Stained and standardized enamel/dentin discs were subjected to one in-office tooth bleaching session (45 min), and the gel was either irradiated or not with V-LED. Thus, the following groups were established (n = 8): G1: No treatment (negative control, NC); G2: 35% H2O2 (positive control, PC); G3: 35%H2O2 + V-LED/15 min; G4: 35%H2O2 + V-LED/30 min; G5: 35%H2O2 + V-LED/45 min. First, esthetic efficacy was assessed (ΔE00 and ΔWI). Discs assembled in artificial pulp chambers were subjected to the same bleaching treatments. Then, the extracts (culture medium + diffused bleaching gel components) were collected and applied to MDPC-23 pulp cells, which were analyzed for viability (Live/Dead, MTT) and oxidative stress (OxS). The amount of H2O2 in the extracts was also determined (leuco crystal-violet/peroxidase). The data were subjected to ANOVA/Tukey at a 5% significance level. Results: Although esthetic efficacy did not differ among the irradiated groups (G3, G4, and G5) (p > 0.05), their results were higher than in G2 (PC; p < 0.05). In the irradiated groups, the cell viability and OxS as well as the amount of H2O2 in the extracts were statistically similar to G2 (PC), regardless of irradiation time (p > 0.05). Conclusion: Although V-LED improves the esthetic outcome of in-office tooth bleaching, increasing irradiation time does not effect the color changes and cytotoxicity of this professional therapy.
BLOCKADE OF AT1 RECEPTORS RESTORE P2/P1 WITHOUT CHANGING INTRACRANIAL PRESSURE IN RENOVASCULAR HYPERTENSIVE RATS WITH 0.3 M NACL AD LIBITUM
(Lippincott Williams & Wilkins, 2023-01-01) Lucera, Gabriela Maria [UNESP]; Pontes, Roberto Braz [UNESP]; Fernandes, Marcos Vinicius [UNESP]; Frigieri, Gustavo; Andrade, Rodrigo; Colombari, Eduardo [UNESP]; Menani, Jose Vanderlei [UNESP]; Colombari, Debora Simoes [UNESP]; Universidade Estadual Paulista (UNESP)
Contractile function of fasting and digesting broad-snouted caiman (Caiman latirostris)
(Canadian Science Publishing, 2023-05-17) Lopes, Andre Guelli [UNESP]; Monteiro, Diana Amaral; Vasconcelos, Eliton da Silva [UNESP]; Kalinin, Ana Lucia; Universidade Federal de São Carlos (UFSCar); Universidade Estadual Paulista (UNESP)
Feeding regimes are a critical process to ensure survival and reproduction, which modulate several behavioral and physiological patterns of ectotherms, especially cardiovascular adjustments. However, crocodilian myocardial contractile function after food intake remains understudied. We investigated the importance of ventricular myocardial contractility during digestion in the broad-snouted caiman, Caiman latirostris Daudin, 1801. Isometric ventricle preparations and Ca2+-handling protein expression were used to investigate the effects of prolonged fasting (30 days) and feeding (48 h after feeding on meals at 15% of body mass) on cardiac function. Upon feeding, there was no significant difference in relative ventricular mass. The cardiac response of the caiman to digestion was characterized by upregulation of the Na+/Ca2+ exchanger expression and an increase in myocardial contractility (positive inotropism and lusitropism) within the physiological range of heart rate. The digesting caiman's ventricular myocardium was able to maintain faster kinetics of contraction and relaxation, allowing for significantly increased cardiac pumping capacity at higher pacing frequencies. Our results demonstrated that the myocardium of broad-snouted caimans exhibits specializations in excitation-contraction coupling, which can provide a means to support high cardiovascular performance during digestion.
Eriodictyol Suppresses Porphyromonas gingivalis-Induced Reactive Oxygen Species Production by Gingival Keratinocytes and the Inflammatory Response of Macrophages
(Frontiers Media Sa, 2022-02-28) Maquera-Huacho, Patricia Milagros [UNESP]; Spolidorio, Denise Palomari [UNESP]; Manthey, John. A. A.; Grenier, Daniel; Univ Laval; Universidade Estadual Paulista (UNESP); USDA
Porphyromonas gingivalis is a key pathogen of periodontitis, an inflammatory disease that affects the tooth-supporting tissues. The aim of the present study was to investigate the effects of the flavanone eriodictyol on P. gingivalis-induced reactive oxygen species (ROS) production by gingival keratinocytes and the inflammatory response of macrophages. Porphyromonas gingivalis and H2O2 acted synergistically to induce ROS production by keratinocytes. The presence of eriodictyol significantly attenuated ROS production in a dose-dependent manner. We used a macrophage model to show that eriodictyol decreases the secretion of IL-1 beta, IL-6, IL-8, and TNF-alpha induced by P. gingivalis. Evidence has been brought that this anti-inflammatory property of eriodictyol may be related to its ability to prevent the activation of the NF-kappa B signaling pathway by P. gingivalis. This periodontal pathogen was also found to be a potent inducer of matrix metalloproteinase (MMP) production by macrophages, including MMP-2, MMP-8, and MMP-9. Eriodictyol dose-dependently inhibited the production of all three MMPs. Lastly, eriodictyol inhibited the catalytic activity of both MMP-9 and P. gingivalis collagenase. In conclusion, eriodictyol may be a potential therapeutic agent for preventing and/or treating periodontal disease due to its antioxidant, anti-inflammatory, and anti-proteinase properties.

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