Estimation of periodontal pocket surface area in small to medium dogs: a proof-of-concept study

Background Periodontal disease is the most common dental disease in dogs. Although the systemic effects of periodontal disease have not been clarified in veterinary science, it is necessary to evaluate the effects of periodontal disease in clinical trials in the future. There have been a few clinical attempts made, however, to assess the severity of periodontal inflammation and its impact on the systemic health of dogs. Meanwhile, in the field of dentistry for humans, the periodontal inflamed surface area (PISA) and periodontal epithelial surface area (PESA) have been used to quantitatively assess the degree of periodontal disease affecting a single tooth as well as the overall extent of periodontitis. Recent studies have also suggested the use of these assessments to examine the relationship between periodontal inflammation and systemic health. Results The estimation formula for a dog’s periodontal pocket surface area (PPSA), an alternative to PISA and PESA in humans, was established using body weight and periodontal pocket depth. Actual values were measured using extracted teeth from various dog breeds and sizes (2.3–25.0 kg of body weight) to obtain universal regression equations for PPSA. Altogether, 625 teeth from 73 dogs of 16 breeds were extracted and subsequently analyzed for morphological information. PPSA was measured in 61 dogs of 10 breeds with periodontal disease using the established estimation formulas, and the correlation between PPSA and preoperative blood chemistry data was analyzed accordingly. A strong correlation was found between PPSA and serum globulin (r = 0.71) while moderate correlations were found for C-reactive protein (r = 0.54) and serum albumin (r = -0.51). Conclusions Estimation formulas using body weight and the 6-point probing depth were established for determining PPSA. Direct correlations between PPSA and several blood test results were observed in the study sample. Taken together, these results suggest that PPSA could be useful for evaluating the effects of periodontitis on systemic conditions in dogs.

Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated.Objective: To determine whether the serum levels of leptin are altered in patients with ECRS.Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient’s serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression.Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05).Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.

Research Progress on the pathogenic mechanism of Streptococcus suis 2

Streptococcus suis (S.suis) is an important zoonotic pathogen that can cause many diseases in pigs, such as sepsis, arthritis, endocarditis, and meningitis, of which meningitis is the most serious. There are 35 serotypes, and serotype two is the most virulent. At the same time, Streptococcus suis serotype 2(SS2) can also infect humans, causing severe public health problems. Although SS2 has attracted significant attention worldwide, the research on its pathogenesis is still limited. The adhesion of pathogenic bacteria to the surface of host cells or tissues and its subsequent invasion and diffusion are the critical steps of pathogenic bacteria. Moreover, the interaction between pathogen and host is involved in these processes. Therefore, to study the pathogenic mechanism of pathogenic bacteria is to study the interaction between pathogenic bacteria and host. This paper described several common virulence factors, such as CPS, SLY, MRP, EF, SAO, Srt, FBPS, SadP, and Eno. Under the actions of virulence factors, SS2 adheres and colonizes to the mucosal and epithelial surface of host cells. Then SS2 invades into deeper tissues and bloodstream. If SS2 in the blood does not cause fatal sepsis, It can go to the third stage. The third stage is to cross the BBB and access the CNS and ultimately causes meningitis. During pathogenesis, SS2 interacts with multiple host cells, such as neutrophils, macrophages, epithelial cells, and microvascular endothelial cells to evade the innate or adaptive immunity of the host.

2Receptor Specific Ligand conjugated Nanocarriers: an Effective Strategy for Targeted Therapy of Tuberculosis

: Tuberculosis (TB) is an ancient chronic disease caused by the bacillus Mycobacterium tuberculosis, which has affected mankind for more than 4,000 years. Compliance with the standard conventional treatment can assure recovery from tuberculosis, but emergence of drug resistant strains pose a great challenge for effective management of tuberculosis. The process of discovery and development of new therapeutic entities with better specificity and efficacy is unpredictable and time consuming. Hence, delivery of pre-existing drugs with improved targetability is the need of the hour. Enhanced delivery and targetability can ascertain improved bioavailability, reduced toxicity, decreased frequency of dosing and therefore better patient compliance. Nanoformulations are being explored for effective delivery of therapeutic agents, however optimum specificity is not guaranteed. In order to achieve specificity, ligands specific to receptors or cellular components of macrophage and Mycobacteria can be conjugatedto nanocarriers. This approach can improve localization of existing drug molecules at the intramacrophageal site where the parasites reside, improve targeting to the unique cell wall structure of Mycobacterium or improve adhesion to epithelial surface of intestine or alveolar tissue (lectins). Present review focuses on the investigation of various ligands like Mannose, Mycolic acid, Lectin, Aptamers etc. installed nanocarriers that are being envisaged for targeting antitubercular drugs.

Embryo-scale epithelial buckling forms a propagating furrow that initiates gastrulation

Cell apical constriction driven by actomyosin contraction forces is a conserved mechanism during tissue folding in embryo development. While much effort has been made to better understand the molecular mechanisms responsible for apical constriction, it is still not clear if apical actomyosin contraction forces are necessary or sufficient per se to drive tissue folding. To tackle this question, we use the Drosophila embryo model system that forms a furrow on the ventral side, initiating mesoderm internalization. Past computational models support the idea that cell apical contraction forces may not be sufficient and that active or passive cell apico-basal forces may be necessary to drive cell wedging and tissue furrowing. By using 3D computational modelling and in toto embryo image analysis and manipulation, we now challenge this idea and show that embryo-scale force balance of the tissue surface, rather than cell-autonomous shape changes, is necessary and sufficient to drive a buckling of the epithelial surface forming a furrow which propagates and initiates embryo gastrulation.

MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection

We previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.

Longitudinal to transverse metachronal wave transitions in an in-vitro model of ciliated bronchial epithelium

Myriads of cilia beat on ciliated epithelia, which are ubiquitous in life. When ciliary beats are synchronized, metachronal waves emerge, whose direction of propagation depends on the living system in an unexplained way. We show on a reconstructed human bronchial epithelium in-vitro that the direction of propagation is determined by the ability of mucus to be transported at the epithelial surface. Numerical simulations show that longitudinal waves maximise the transport of mucus while transverse waves, observed when the mucus is rigid and still, minimize the energy dissipated by the cilia.

Tandem repeats structure of gel-forming mucin domains could be revealed by SMRT sequencing data

Mucins are large glycoproteins that cover and protect epithelial surface of the body. Gel-forming mucin domains of mucin genes are rich in proline, threonine, and serine that are heavily glycosylate. These domains show great complexity with tandem repeats (TRs), thus make it difficult to study the sequences. With the coming of single molecule real-time (SMRT) sequencing technologies, we manage to present sequence structure of mucin domains via SMRT long reads for gel-forming mucins MUC2, MUC5AC, MUC5B and MUC6. Our study shows that for different individuals, single nucleotide polymorphisms (SNPs) could be found in mucin domains of MUC2, MUC5AC, MUC5B and MUC6, while different number of tandem repeats could be found in mucin domains of MUC2 and MUC6. Furthermore, we get the sequence of MUC2, MUC5AC, and MUC5B mucin domain in a Chinese individual at accuracy of possibly maximum 99.98%, 99.93%, and 99.76%, respectively. We report a new method to obtain DNA sequence of gel-forming mucin domains. This method will provided new insights on getting the sequence for Tandem Repeat parts which locate in coding region. With the sequences we obtained with this method, we can give more information for people to study the sequences of gel-forming mucin domains.

PATHOLOGICAL STUDY OF LOCALLY ISOLATED FOWL POXVIRUS -EXPERIMENTALLY INFECTED TRACHEA USING SCANNING ELECTRON MICROSCOPY

In this study fowl poxvirus has been isolated from naturally infected birds. This virus induced respiratory distress, 2, 3 and 4 days post inoculation, in intratracheally inoculated 8 week old chickens, these respiratory distress include congestion of tracheal mucosa, increased tracheal secreation and whitish-yellowish pastules appeared at ninth day post inoculation in the upper part of the trachea forming diphtheritic or pseudodiphtheritic membrane. Using scanning electron microscopy to study the changes that occurs in the epithelial surface of trachea. It was found that the virus causes proliferation of epithelial cells forming cluster like papilloma, deciliation and activation of goblet cells.

The Role of Surface in the Pathogenesis and Treatment of COVID-19

Recently, an inverse relationship between incidence of COVID-19 and seasonal aerosolization of mold spores was demonstrated. Analyses of that relationship suggested mold spores compete with SARS-CoV-2 virions for a receptor on the pulmonary epithelial surface. By inference, the operative receptor was proposed to be Toll-like receptor 4, with surface-localized virions being responsible for symptomatology. In this report, the pathogenesis of COVID-19 is further developed, with a focus on a role for surfactant protein D in the process. This developed proposal provides both mechanistic understanding and suggested treatments of COVID-19.