The impact of Lacticaseibacillus paracasei GMNL-143 toothpaste on gingivitis and oral microbiota in adults: a randomized, double-blind, crossover, placebo-controlled trial.

BACKGROUND: This study examines the oral health benefits of heat-killed Lacticaseibacillus paracasei GMNL-143, particularly its potential in oral microbiota alterations and gingivitis improvement. METHODS: We assessed GMNL-143's in vitro interactions with oral pathogens and its ability to prevent pathogen adherence to gingival cells. A randomized, double-blind, crossover clinical trial was performed on gingivitis patients using GMNL-143 toothpaste or placebo for four weeks, followed by a crossover after a washout. RESULTS: GMNL-143 showed coaggregation with oral pathogens in vitro, linked to its surface layer protein. In patients, GMNL-143 toothpaste lowered the gingival index and reduced Streptococcus mutans in crevicular fluid. A positive relationship was found between Aggregatibacter actinomycetemcomitans and gingival index changes, and a negative one between Campylobacter and gingival index changes in plaque. CONCLUSION: GMNL-143 toothpaste may shift oral bacterial composition towards a healthier state, suggesting its potential in managing mild to moderate gingivitis. TRIAL REGISTRATION: ID NCT04190485 ( https://clinicaltrials.gov/ ); 09/12/2019, retrospective registration.

Neutrophil extracellular trap production and CCL4L2 expression influence corticosteroid response in asthma.

The association between neutrophil extracellular traps (NETs) and response to inhaled corticosteroids (ICS) in asthma is unclear. To better understand this relationship, we analyzed the blood transcriptomes from children with controlled and uncontrolled asthma in the Taiwanese Consortium of Childhood Asthma Study using weighted gene coexpression network analysis and pathway enrichment methods. We identified 298 uncontrolled asthma-specific differentially expressed genes and one gene module associated with neutrophil-mediated immunity, highlighting a potential role for neutrophils in uncontrolled asthma. We also found that NET abundance was associated with nonresponse to ICS in patients. In a neutrophilic airway inflammation murine model, steroid treatment could not suppress neutrophilic inflammation and airway hyperreactivity. However, NET disruption with deoxyribonuclease I (DNase I) efficiently inhibited airway hyperreactivity and inflammation. Using neutrophil-specific transcriptomic profiles, we found that CCL4L2 was associated with ICS nonresponse in asthma, which was validated in human and murine lung tissue. CCL4L2 expression was also negatively correlated with pulmonary function change after ICS treatment. In summary, steroids fail to suppress neutrophilic airway inflammation, highlighting the potential need to use alternative therapies such as leukotriene receptor antagonists or DNase I that target the neutrophil-associated phenotype. Furthermore, these results highlight CCL4L2 as a potential therapeutic target for individuals with asthma refractory to ICS.

Serine-/Cysteine-Based sp2-Iminoglycolipids as Novel TLR4 Agonists: Evaluation of Their Adjuvancy and Immunotherapeutic Properties in a Murine Model of Asthma.

Glycolipids with TLR4 agonistic properties can serve either as therapeutic agents or as vaccine adjuvants by stimulating the development of proinflammatory responses. Translating them to the clinical setting is hampered by synthetic difficulties, the lack of stability in biological media, and/or a suboptimal profile of balanced immune mediator secretion. Here, we show that replacement of the sugar fragment by an sp2-iminosugar moiety in a prototypic TLR4 agonist, CCL-34, yields iminoglycolipid analogues that retain or improve their biological activity in vitro and in vivo and can be accessed through scalable protocols with total stereoselectivity. Their adjuvant potential is manifested in their ability to induce the secretion of proinflammatory cytokines, prime the maturation of dendritic cells, and promote the proliferation of CD8+ T cells, pertaining to a Th1-biased profile. Additionally, their therapeutic potential for the treatment of asthma, a Th2-dominated inflammatory pathology, has been confirmed in an ovalbumin-induced airway hyperreactivity mouse model.

Off-Resonance SERS Nanoprobe-Targeted Screen of Biomarkers for Antigens Recognition of Bladder Normal and Aggressive Cancer Cells.

The discovery of different binding receptors to allow rapid and high-sensitivity detection via a noninvasive urine test has become the goal for urothelial carcinoma (UC) diagnosis and surveillance. In this study, we developed a new screening membrane receptor platform for bladder cancer cells by integrating surface-enhanced Raman spectroscopy (SERS) with 4-aminothiophenol (4-ATP)-modified AuAg nanohollows upon NIR laser excitation. AuAg nanohollows have an absorption band at ∼630 nm, and slightly off-resonance 785 nm laser excitation is used for minimal photothermal effect. Using the same carbodiimide cross-linker chemistry to conjugate anti-EGFR, transferrin (TF), 4-carboxyphenylboronic acid (CPBA), folic acid (FA), and hyaluronic acid (HA) molecules, by screening the 4-ATP SERS signals intensity, we demonstrated that the targeting efficiency with the cost-effective CPBA molecule is comparable with the conjugation of anti-EGFR antibody to aggressive T24 cancer cells (high-grade), while weak intensity 4-ATP SERS responses to targets were obtained by grade-I RT4 bladder cancer cells, NIH/3T3 fibroblast cells, and SV-HUC1 bladder normal cells. This SERS nanoprobe platform makes primary bladder carcinoma screening from in vitro to ex vivo more straightforward. Our demonstration offers exciting potential for SERS screening of specific receptors on cancer cells of different grades and facilitates new opportunities ranging from surface engineering of SERS material tags to SERS imaging-guided and targeted phototherapy of cancer cells by controlling the laser powers.

New Templated Ostwald Ripening Process of Mesostructured FeOOH for Third-Harmonic Generation Bioimaging.

Emerging advances in iron oxide nanoparticles exploit their high magnetization for various applications, such as bioseparation, hyperthermia, and magnetic resonance imaging. In contrast to their excellent magnetic performance, the harmonic generation and luminescence properties of iron oxide nanoparticles have not been thoroughly explored, thus limiting their development as a tool in photomedicine. In this work, a seed/growth-inspired synthesis is developed combined with primary mineralization and a ligand-assisted secondary growth strategy to prepare mesostructured α-FeOOH nanorods (NRs). The sub-wavelength heterogeneity of the refractive index leads to enhanced third-harmonic generation (THG) signals under near-infrared excited wavelengths at 1230 nm. The as-prepared NRs exhibit an 11-fold stronger THG intensity compared to bare α-FeOOH NRs. Using these unique nonlinear optical properties, it is demonstrated that mesostructured α-FeOOH NRs can serve as biocompatible and nonbleaching contrast agents in THG microscopy for long-term labeling of cells as well as in angiography in vivo by modifying lectin to enhance the binding efficiency to the glycocalyx layers on the wall of blood vessels. These results provide a new insight into Fe-based nanoplatforms capable of emitting coherent light as molecular probes in optical microscopy, thus establishing a complementary microscopic imaging method for macroscopic magnetic imaging systems.

Assembled growth of 3D Fe3O4@Au nanoparticles for efficient photothermal ablation and SERS detection of microorganisms.

The development of a single agent with multifunctionality for the rapid detection and inhibition of the spread of pathogenic microorganisms is of great importance for environmental hygiene as well as water and food safety. For this purpose, we integrate plasmonic nano-Au, near-infrared (NIR)-activated Fe3O4 nanoclusters, and NIR-absorbing polydopamine to form a leukocyte-like Fe3O4@Au nanostructure to treat microorganisms. Through high-temperature reduction of HAuCl4 with l-dopamine, Au atoms are spontaneously generated along with Fe3O4 nanoclusters via a site-selected atom deposition process between the Au(111) and Fe3O4(222) lattice planes. Combining the magnetic properties of Fe3O4 and the optical functionality of gold nanoparticles, the Fe3O4@Au nanohybrid exhibits effective photothermal conversion and magnetism-guided aggregation to improve the molecular surface-enhanced Raman scattering (SERS) signal, achieving a limit of detection on the micromolar to nanomolar level for methylene blue (MB) and 4-aminothiophenol (4-ATP). After magnetism-assisted adsorption, we adopt Escherichia coli (E. coli) as a model analyte and demonstrate label-free SERS sensing of bacterial cell molecular structures based on optical fingerprints and recyclable photothermal ablation of bacterial pathogens (Gram-positive, Gram-negative, and anaerobic bacteria).

Targeting FXYD2 by cardiac glycosides potently blocks tumor growth in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is an aggressive neoplasm with a high recurrence rate that frequently develops resistance to platinum-based chemotherapy. There are few prognostic biomarkers or targeted therapies exist for patients with OCCC. Here, we identified that FXYD2, the modulating subunit of Na+/K+-ATPases, was highly and specifically expressed in clinical OCCC tissues. The expression levels of FXYD2 were significantly higher in advanced-stage of OCCC and positively correlated with patients' prognoses. Silencing of FXYD2 expression in OCCC cells inhibited Na+/K+-ATPase enzyme activity and suppressed tumor growth via induction of autophagy-mediated cell death. We found that high FXYD2 expression in OCCC was transcriptionally regulated by the transcriptional factor HNF1B. Furthermore, up-regulation of FXYD2 expression significantly increased the sensitivity of OCCC cells to cardiac glycosides, the Na+/K+-ATPase inhibitors. Two cardiac glycosides, digoxin and digitoxin, had a great therapeutic efficacy in OCCC cells in vitro and in vivo. Taken together, our results demonstrate that FXYD2 is functionally upregulated in OCCC and may serve as a promising prognostic biomarker and therapeutic target of cardiac glycosides in OCCC.

α-Catulin drives metastasis by activating ILK and driving an αvß3 integrin signaling axis.

α-Catulin is an oncoprotein that helps sustain proliferation by preventing cellular senescence. Here, we report that α-catulin also drives malignant invasion and metastasis. α-Catulin was upregulated in highly invasive non-small cell lung cancer (NSCLC) cell lines, where its ectopic expression or short-hairpin RNA-mediated attenuation enhanced or limited invasion or metastasis, respectively. α-Catulin interacted with integrin-linked kinase (ILK), a serine/threonine protein kinase implicated in cancer cell proliferation, antiapoptosis, invasion, and angiogenesis. Attenuation of ILK or α-catulin reciprocally blocked cell migration and invasion induced by the other protein. Mechanistic investigations revealed that α-catulin activated Akt-NF-κB signaling downstream of ILK, which in turn led to increased expression of fibronectin and integrin αvß3. Pharmacologic or antibody-mediated blockade of NF-κB or αvß3 was sufficient to inhibit α-catulin-induced cell migration and invasion. Clinically, high levels of expression of α-catulin and ILK were associated with poor overall survival in patients with NSCLC. Taken together, our study shows that α-catulin plays a critical role in cancer metastasis by activating the ILK-mediated Akt-NF-κB-αvß3 signaling axis.

Ileocolon graft pedicled on ileocolic artery: an alternative esophageal substitute for corrosive injury.

A variety of bowel interpositions have been well-developed for esophageal replacement surgery. However the choices are often limited in the case of alimentary corrosive injury due to frequent associated injuries. Herein we present a case of caustic injury with compromised mesocolon. Successful reconstruction of the alimentary integrity was accomplished using an ileocolic graft pedicled on an ileocolic artery.

Acid corrosive injury in patients with a history of partial gastrectomy: outcome analysis.

BACKGROUND: Our purpose was to delineate the characteristics and outcome of acid-corrosive injury in patients with a history of gastric resection. MATERIAL AND METHODS: A total of 359 patients with a history of acid-corrosive injury were retrospectively reviewed. They were grouped based on past history with group 1 consisting of 8 patients with a history of gastric surgery (6 hemigastrectomies with Billroth II gastrojejunostomy, 2 partial gastrectomies with Billroth I gastroduodenostomy) and group 2 consisting of 351 patients without a history of previous gastric surgery. Clinical data, operative findings, treatment modalities and prognoses were compared. RESULTS: Group 1 patients required significantly more emergency surgical interventions (p=0.016) and more frequent resection of alimentary necrosis (p=0.007). In the operative findings of those undergoing emergency laparotomy, group 1 had a slightly higher incidence of total gastric necrosis with or without perforation (p=0.388), and a higher incidence of jejunal resection (p=0.001). However, group 1 patients had a relatively lower operative mortality rate compared to group 2 patients (p=0.640). CONCLUSION: Acid-injured patients with a history of previous gastric surgery tended to have a higher incidence of mandatory emergency surgical exploration and resection of the alimentary tract. With early and prompt management, a good survival rate can still be anticipated.