Tailored Viral-like Particles as Drivers of Medical Breakthroughs.

Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and marketed. Virus-like particles (VLPs) have emerged as promising alternatives to conventional nanoparticles due to their safety, biocompatibility, immunogenicity, structural stability, scalability, and versatility. Furthermore, VLPs can be surface-functionalized with small molecules to improve circulation half-life and target specificity. Through the functionalization and coating of VLPs, it is possible to optimize the response properties to a given stimulus, such as heat, pH, an alternating magnetic field, or even enzymes. Surface functionalization can also modulate other properties, such as biocompatibility, stability, and specificity, deeming VLPs as potential vaccine candidates or delivery systems. This review aims to address the different types of surface functionalization of VLPs, highlighting the more recent cutting-edge technologies that have been explored for the design of tailored VLPs, their importance, and their consequent applicability in the medical field.

Tocolytic action and underlying mechanism of galetin 3,6-dimethyl ether on rat uterus.

BACKGROUND: Galetin 3,6-dimethyl ether (FGAL) is a flavonoid isolated from aerial parts of Piptadenia stipulacea. Previously, FGAL was shown to inhibit both carbachol- and oxytocin-induced phasic contractions in the rat uterus, which was more potent with oxytocin. Thus, in this study, we aimed to investigate the tocolytic action mechanism of FGAL on the rat uterus. METHODS: Segments of rat uterus ileum were suspended in organ bath containing modified Locke-Ringer solution at 32 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer. RESULTS: FGAL was more potent in relaxing uterus pre-contracted with oxytocin than with KCl. Additionally, FGAL shifted oxytocin-induced cumulative contractions curves to the right in a non-parallel manner, with Emax reduction, indicating a pseudo-irreversible noncompetitive antagonism of oxytocin receptors (OTR) or a downstream pathway target. Moreover, FGAL shifted CaCl2-induced cumulative contraction curves to the right in a non-parallel manner in depolarizing medium, nominally without Ca2+, with Emax reduction, suggesting the inhibition of Ca2+ influx through CaV. The relaxant potency of FGAL was reduced by CsCl, a non-selective K+ channel blocker, suggesting positive modulation of these channels. Furthermore, in presence of apamin, 4-aminopyridine, glibenclamide or 1 mM TEA+, the relaxant potency of FGAL was attenuated, indicating the participation of SKCa, KV, KATP and highlighting BKCa. Aminophylline, a non-selective phosphodiesterase (PDE) blocker, did not affect the FGAL relaxant potency, excluding the modulation of cyclic nucleotide PDEs pathway by FGAL. CONCLUSION: Tocolytic effect of FGAL on rat uterus occurs by pseudo-irreversible noncompetitive antagonism of OTR and activation of K+ channels, primarily BKCa, leading to calcium influx reduction through CaV.

Multidisciplinary Treatment of a Fenestration-type Defect.

The case report aimed at treating a fenestration-type defect with multidisciplinary conventional and advanced surgical techniques. Fenestrations are isolated areas in which the exposed root surface is covered only by the periosteum and gingiva, but the remaining cortical bone remains intact. Root coverage is indicated in cases of root hypersensitivity, treatment of shallow caries lesions, cervical abrasions, and esthetic and cosmetic needs. In this case report, after proper hygiene instruction and dental biofilm control, a fenestration-type defect was treated using guided tissue regeneration (anorganic bovine matrix and resorbable membrane) and a connective tissue grafts, associated to an endodontic apicoectomy. After reevaluation, the remaining gingival recession was treated with a second gingival connective tissue graft covered with q double papillae type in order to reconstruct the periodontal tissues of the involved tooth. In this clinical case, the interaction between the different areas of dentistry has made it possible to correct a fenestration-type defect, following procedures based on scientific evidence, restoring periodontal health, esthetics, self-esteem, and meeting the patient's expectations regarding her initial complaint. This case report shows the important role of interdisciplinary approach to treating a patient with a complex periodontal defect that required different types of knowledge and abilities to achieve the best results based on the current status of dentistry possibilities.

Acute Treatment with Lauric Acid Reduces Blood Pressure and Oxidative Stress in Spontaneously Hypertensive Rats.

The effects of acute administration of lauric acid (LA), the most abundant medium-chain fatty acid of coconut oil, on blood pressure, heart rate and oxidative stress were investigated in spontaneously hypertensive rats (SHR). Intravenous doses of LA reduced blood pressure in a dose-dependent fashion (1, 3, 4, 8 and 10 mg/kg) in both SHR and Wistar Kyoto rats. LA (10-8 to 3 × 10-3 M) induced vasorelaxation in isolated superior mesenteric artery rings of SHR in the presence (n = 7) or absence (n = 8) of functional endothelium [maximum effect (ME) = 104 ± 3 versus 103 ± 4%]. After exposure to KCl (60 mM), LA also induced concentration-dependent vasorelaxation (n = 7) compared to that under Phe-induced contraction (ME = 113.5 + 5.1 versus 104.5 + 4.0%). Furthermore, LA-induced vasorelaxation in vessels contracted with S(-)-BayK8644 (200 nM), a L-type Ca2+ channel agonist (ME = 91.4 + 4.3 versus 104.5 + 4.0%, n = 7). Lastly, LA (10-3 M) reduced NADPH-dependent superoxide accumulation in the heart (18 ± 1 versus 25 ± 1 MLU/min/µg protein, n = 4, p < 0.05) and kidney (82 ± 3 versus 99 ± 4 MLU/min/µg protein, n = 4, p < 0.05). Our data show that LA reduces blood pressure in normotensive and hypertensive rats. In SHR, this effect might involve Ca+2 channels in the resistance vessels and by its capability of reducing oxidative stress in heart and kidneys.

Spasmolytic activity of trachylobanes ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid isolated from Xylopia langsdorfiana A. St-Hil. & Tul. (Annonaceae).

We aimed to investigate the possible spasmolytic activity of ent-7α-acetoxytrachyloban-18-oic acid (1) and ent-7α-hydroxytrachyloban-18-oic acid (2) on smooth muscle models. In male rat aorta and rat uterus, both diterpenes were unable to trigger spasmolytic action. However, 2 relaxed guinea-pig trachea: Compounds 1 and 2 antagonised, significantly and concentration-dependently, carbachol- and histamine-induced phasic contractions in guinea-pig ileum. Moreover, they induced a significant and concentration-dependent relaxation in pre-contracted (KCl, carbachol or histamine) guinea-pig ileum, with 2 being 15 times more potent than 1 in histamine-contracted ileum. These dissimilar results may be due to chemical differences between them. Thus, we demonstrated that 1 and 2 seem to be promising spasmolytic agents, although further studies are required to elucidate the spasmolytic action mechanism.

Ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K(+) and Ca(2+) channels to reduce cytosolic calcium concentration on guinea pig ileum.

In this study we investigated the mechanism underlying the spasmolytic action of ent-7α-acetoxytrachyloban-18-oic acid (trachylobane-360) and ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318), diterpenes obtained from Xylopia langsdorfiana, on guinea pig ileum. Both compounds inhibited histamine-induced cumulative contractions (slope=3.5±0.9 and 4.4±0.7) that suggests a noncompetitive antagonism to histaminergic receptors. CaCl(2)-induced contractions were nonparallelly and concentration-dependently reduced by both diterpenes, indicating blockade of calcium influx through voltage-dependent calcium channels (Ca(v)). The Ca(v) participation was confirmed since both trachylobanes equipotently relaxed ileum pre-contracted with S-(-)-Bay K8644 (EC(50)=3.5±0.7×10-(5) and 1.1±0.2×10-(5)M) and KCl (EC(50)=5.5±0.3×10-(5) and 1.4±0.2×10-(5)M). K(+) channels participation was confirmed since diterpene-induced relaxation curves were significantly shifted to right in the presence of 5mM tetraethylammonium (TEA(+)) (EC(50)=0.5±0.04×10-(4) and 2.0±0.5×10-(5)M). ATP-sensitive K(+) channel (K(ATP)), voltage activated K(+) channels (K(V)), small conductance calcium-activated K(+) channels (SK(Ca)) or big conductance calcium-activated K(+) channels (BK(Ca)) did not seem to participate of trachylobane-360 spasmolytic action. However trachylobane-318 modulated positively K(ATP), K(V) and SK(Ca) (EC(50)=1.1±0.3×10-(5), 0.7±0.2×10-(5) and 0.7±0.2×10-(5)M), but not BK(Ca). A fluorescence analysis technique confirmed the decrease of cytosolic calcium concentration ([Ca(2+)](c)) induced by both trachylobanes in ileal myocytes. In conclusion, trachylobane-360 and trachylobane-318 induced spasmolytic activity by K(+) channel positive modulation and Ca(2+) channel blockade, which results in [Ca(2+)](c) reduction at cellular level leading to smooth muscle relaxation.

Análise clínica, tomográfica e histológica comparativa entre BoneCeramic e Bio-Oss, utilizados como enxertos após a elevação da mucosa do seio maxilar em humanos: relato de caso clínico com desenho do tipo boca dividida, acompanhado durante oito meses / Clinical, tomographic and histological comparison of BoneCeramic and Bio-Oss used for sinus lift procedures in humans: case report of a split-mouth design with a 8-month follow-up

O objetivo deste estudo foi apresentar um caso clínico, suportado por achados tomográficos e histológicos, de regiões enxertadas com HA+β-TCP (hidroxiapatita + beta fosfato tricálcio, BoneCeramic) ou osso bovino inorgânico liofilizado (Bio-Oss), em um procedimento de elevação bilateral da mucosa do seio maxilar. A necessidade de enxerto ósseo, para viabilizar a instalação de implantes na maxila posterior foi comprovada pela altura óssea residual inferior a 5 mm, bilateralmente, avaliada por tomografia computadorizada de feixe cônico em paciente edêntulo total, usuário de prótese total convencional. Após a osteotomia de acesso ao seio maxilar e o descolamento da mucosa sinusal, foi realizado o preenchimento da cavidade com substituto ósseo bovino inorgânico liofilizado (Bio-Oss) na maxila direita e com HA+β-TCP (BoneCeramic) na maxila esquerda. Nova tomografia computadorizada foi realizada oito meses após o procedimento de enxertia, e demonstrou ganho de tecido mineralizado em altura nas regiões enxertadas, compatível com a instalação de implantes. No ato da instalação dos implantes foram obtidas biópsias das áreas enxertadas com auxílio de broca trefina. A análise histológica demonstrou que, nas áreas em que ambos os enxertos foram realizados, havia remanescente do biomaterial sempre rodeado por tecido ósseo neoformado e tecido conjuntivo mole. Entretanto, a análise qualitativa subjetiva sugere uma tendência maior de presença de material mineralizado quando o osso bovino inorgânico liofilizado (Bio-Oss) foi utilizado. Dentro do limite deste estudo, pôde-se concluir que ambos os materiais, quando utilizados em procedimentos de enxertia para aumento ósseo no assoalho do seio maxilar em humanos, foram capazes de promover o ganho em altura óssea, apresentando comportamento clínico e tomográfico semelhantes depois de oito meses.

The aim of this study was to report a clinical case, supported by CBCT and histological findings, of regions grafted with HA + β-TCP (hydroxyapatite + beta tricalcium phosphate, BoneCeramic) or inorganic bovine bone lyophilized (Bio-Oss) for bilateral maxillary sinus lifting. The need for bone grafting in the posterior maxilla was confirmed by residual bone heights of less than 5 mm, in a totally edentulous patient, wearing a conventional total prosthesis. After osteotomy and detachment of the sinus mucosa, the formed cavities were filled with Bio-Oss (right side) and BoneCeramic (left side). A new CBCT scan was performed eight months after grafting procedure, and demonstrated gain of mineralized tissue height in the grafted regions, consistent with placement implant. After installation of the implants, biopsies were retrieved from the grafted areas with the aid of a trephine bur. Histological analysis demonstrated that, remaining biomaterial particles were always surrounded by newly formed bone and soft tissue in both sides. However, the subjective qualitative analysis suggests the presence of a larger trend of mineralized material when lyophilized inorganic bovine bone (Bio-Oss) was used. Within the limits of this study, it can be concluded that both materials were able to promote significant gain in bone maxillary height after eight months.