Correction: Restoring the electrical microenvironment using ferroelectric nanocomposite membranes to enhance alveolar ridge regeneration in a mini-pig preclinical model.

Correction for 'Restoring the electrical microenvironment using ferroelectric nanocomposite membranes to enhance alveolar ridge regeneration in a mini-pig preclinical model' by Yiping Li et al., J. Mater. Chem. B, 2023, 11, 985-997, https://doi.org/10.1039/D2TB02054H.

Restoring the electrical microenvironment using ferroelectric nanocomposite membranes to enhance alveolar ridge regeneration in a mini-pig preclinical model.

The maintenance and incremental growth of the alveolar bone at the tooth extraction site, to achieve the required height and width for implant restoration, remains a major clinical challenge. Here, the concept of restoring the electrical microenvironment to improve the effects of alveolar ridge preservation (ARP) was investigated in a mini-pig preclinical model. The endogeneous electrical microenvironment of the dental alveolar socket was recapitulated by fabricating a biomimetic ferroelectric BaTiO3/poly(vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) non-resorbable nanocomposite membrane polarized by corona poling. The polarized nanocomposite membrane exhibited excellent electrical stability. After implantation with bone grafts and covering with the charged membrane in tooth extraction sites for three months, both the vertical and horizontal dimension resorption of the alveolar ridge were significantly prevented, as assessed by cone beam computed tomography (CBCT) analyses. Micro-CT analysis showed that the charged membrane induced significant enhancement of newly regenerated bone at the tooth extraction sites. Histological analysis further confirmed that the restoration of the electrical microenvironment significantly promoted buccal alveolar bone regeneration and maturation. In addition, the charged membranes can maintain their structural integrity during the entire implantation period and exhibit positive long-term systemic safety, as assessed by preclinical sub-chronic systemic toxicity. These findings thus provide an innovative strategy for restoring the electrical microenvironment to enhance ARP following dentition defect and edentulism, which could further advance prosthodontics implant technology.

Helicobacter pylori promotes inflammatory factor secretion and lung injury through VacA exotoxin-mediated activation of NF-κB signaling.

Previous reports have shown that Helicobacter pylori (H. pylori) infection is associated with respiratory diseases. However, the pathogenesis remains unclear. Vacuolating cytotoxin A (VacA) is a major H. pylori exotoxin. In this study, we investigated the signaling pathways involved in the inflammatory response to H. pylori infection and VacA. Mice were treated with H. pylori and VacA, and histopathological analysis of lung tissues was performed using hematoxylin-eosin, Masson's trichrome, and periodic acid Schiff staining. The secretion of inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay. The expression of VacA, nuclear factor-kappa B (NF-κB), and p65 NF-κB was analyzed by Western blotting and immunofluorescence. Cell proliferation and apoptosis were assessed using the MTS assay and flow cytometry, respectively. In mice, H. pylori infection and VacA treatment promoted the secretion of the inflammatory factors interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), IL-6, and IL-8, increased p65 NF-κB protein phosphorylation, and induced lung injury. Furthermore, H. pylori infection promoted VacA production. In an in vitro cell model, VacA treatment significantly suppressed the proliferation of WI-38 and BEAS-2B cells, promoted apoptosis, induced TNF-α, IL-1ß, IL-6, and IL-8 secretion, and promoted p65 NF-κB protein phosphorylation and NF-κB nuclear transfer. The NF-κB inhibitor BAY11-7082 alleviated VacA-induced inflammation and apoptosis and increased cell viability. In conclusion, VacA promotes the secretion of inflammatory factors and induces lung injury through NF-κB signaling.

Minimum inhibitory concentrations of commonly used antibiotics against Helicobacter Pylori: A multicenter study in South China.

AIM: To determine the minimum inhibitory concentrations (MICs) of commonly used antibiotics against Helicobacter Pylori (H. pylori) in South China and compare their resistance rates by using EUCAST breakpoints and other breakpoints. METHODS: Patients who had not previously received H. pylori treatment in clinical centers in South China were enrolled in this study from 2017 to 2020. Gastric biopsies were obtained for H. pylori culture. The MICs of amoxicillin (AMX), clarithromycin (CLA), metronidazole (MTZ), levofloxacin (LEV), tetracycline (TET) and furazolidone (FZD) were tested by broth microdilution method and assessed by two different breakpoints. ATCC43504 standard strain served as a control. RESULTS: A total of 208 H. pylori strains were isolated from patients' biopsy samples. The MICs of AMX, CLA, MTZ, LEV, TET and FZD for H. pylori were 0.0156-256mg/L (MIC50 0.125mg/L, MIC90 4mg/L), 0.0156- >256 mg/L (MIC50 0.0312mg/L, MIC90 64mg/L), 0.0156- >256mg/L (MIC50 8mg/L, MIC90 256mg/L), 0.0156-256mg/L (MIC50 0.25mg/L, MIC90 16mg/L), 0.0156-256mg/L (MIC50 0.0625mg/L, MIC90 4mg/L), and 0.0156- >256mg/L (MIC50 0.0312mg/L, MIC90 2mg/L), respectively. The MICs of AMX, CLA, MTZ, LEV, TET and FZD for ATCC43504 strain were 0.25mg/L, 0.0625mg/L, 64mg/L, 0.5mg/L, 1mg/L and 0.25mg/L, respectively. The resistance rate of FZD was 11.05%. The overall resistance rates according to EUCAST breakpoints and other breakpoints were 57.21% and 14.90% for AMX (p<0.001), 38.94% and 38.94% for CLA (p = 1), 39.42% and 50.96% for MTZ (p<0.001), 12.98% and 10.58% for TET (p = 0.025), 35.10% and 35.10% for LEV (p = 1), respectively. CONCLUSIONS: Our results demonstrate that AMX, FZD, and TET, but not MTZ, CLR or LEV, showed good anti-H. pylori activity in vitro in South China. When different breakpoints were used, similar results were found with CLA, and LEV, but not with AMX, MTZ, or TET.

Down-regulation of lncTCF7 inhibits cell migration and invasion in colorectal cancer via inhibiting TCF7 expression.

The prognosis of colorectal cancer (CRC) is still very poor, owing to the high incidence of metastasis. Long noncoding RNA TCF7 (lncTCF7) has been shown to play critical roles in human CRC development and progression, but the molecular mechanisms of lncTCF7 in CRC are still unknown. This study aimed to explore the functions and molecular mechanisms of lncTCF7 on the migration and invasion of CRC cells. Notably, lncTCF7 was highly expressed in CRC cell lines relative to normal colonic epithelial cells. LncTCF7 knockdown significantly inhibited migration and invasion of CRC cells. In addition, TCF7 was highly expressed in CRC cell lines relative to that in normal colonic epithelial cells and its expression was significantly decreased in CRC cells transfected with si-lncTCF7. RNA immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assays showed that LncTCF7 recruits BAF170 to activate the TCF7 promoter and regulate TCF7 expression. TCF7 overexpression could promote migration and invasion in CRC cells transfected with si-lncTCF7, which reversed the effect of lncTCF7 on the migration and invasion of CRC cells. In conclusion, our data indicate that the downregulation of lncTCF7 significantly inhibits migration and invasion of CRC cells by inhibiting TCF7 expression, suggesting that lncTCF7 may be a potential target for CRC therapy.

Ezrin enhancer knockout inhibits the proliferation and migration of human esophageal carcinoma Eca-109 cells / 中国肿瘤生物治疗杂志

@#Objective: To investigate the effects of ezrin enhancer knockout on ezrin gene expression, cell proliferation and migration of human esophageal carcinoma Eca-109 cells. @*@#Methods: The CRISPR/Cas9 recombinant plasmids targeting upstream/downstream of human ezrin enhancer were co-transfected into human esophageal carcinoma Eca-109 cells, and the cell line Eca-C2 with ezrin enhancer knockout was screened by purinomycin. Then the expression levels of ezrin mRNAand protein in Eca-C2 cells were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively; The expression levels of MAPK-pathway-related proteins were detected by protein array technology; and the effects of ezrin enhancer knockout on the proliferation and migration of Eca-C2 cells were analyzed by WST-1 method and wound-healing assay, respectively. @*@# Results:The human esophageal carcinoma cell line Eca-C2 with stable ezrin enhancer knockout was established successfully. Compared with control cells, the mRNA and protein expressions of ezrin in Eca-C2 cells were significantly reduced (all P<0.05).Among the 17 detected MAPK pathway related proteins in Eca-C2 cells, 9 proteins (AKT, CREB, GSK3b, MKK6, mTOR, P38, P53, P70S6K and RSK1) were down-regulated, and the cell proliferation and migration were significantly inhibited (all P<0.05).@*@# Conclusion: ezrin enhancer knockout can significantly inhibit the cell proliferation and migration of human esophageal carcinoma Eca-109 cells.

Effects of deer age on the physicochemical properties of deproteinized antler cancellous bone: an approach to optimize osteoconductivity of bone graft.

Inorganic bone xenograft materials have recently found extensive surgical application in the clinic. Previously we have demonstrated that calcinated antler cancellous bone (CACB) has great potential for bone defect repair, due to the similar structure and composition compared with human bone. However, the effect of intrinsic material characteristics, particularly deer age, on the physicochemical and biological properties of CACB scaffolds has not been clarified. The aim of this study is to investigate the structure, composition and in vitro solubility of CACB scaffolds derived from deer of varying ages, including young (CACB-Y), middle-aged (CACB-M), and old (CACB-O) deer, and to determine subsequent biological performance. Microstructural analyses showed looser crystal arrangement and lower porosity in CACB-M compared to CACB-Y and CACB-O. Phase-structure analysis showed that CACB-M had the largest crystal size. Component characterization results showed that CACB-M had the most carbonated substitute and the highest content of trace elements (Na, Fe). The in vitro solubility test showed that CACB-M had the fastest dissolution and apatite deposition rates with new crystalline phases. In addition, CACB-M could be conducive for attachment, proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro, as well as conducive for bone regeneration in vivo. These findings indicate that animal age should be seriously considered as a key parameter in optimizing the physicochemical and biological properties of deproteinized antler cancellous bone substitutes for bone regeneration applications.

Modified sequential therapy vs quadruple therapy as initial therapy in patients with Helicobacter infection.

AIM: To evaluate the efficacy and safety of modified sequential therapy and to compare modified sequential therapy with standard quadruple therapy for Helicobacter pylori (H. pylori) eradication. METHODS: In total, 200 consecutive patients who were diagnosed with H. pylori-infected chronic gastritis by electronic endoscopy and rapid urease testing from December 2012 to October 2013 were enrolled in this study. The patients had not previously received H. pylori eradication treatment, and were randomized into two groups. The patients in Group A (n = 101) were treated with ilaprazole + bismuth potassium citrate + amoxicillin and clavulanate potassium + levofloxacin, and the patients in Group B (n = 99) were administered a modified sequential therapy composed of ilaprazole at 5 mg bid and amoxicillin and clavulanate potassium at 914 mg for the first five days followed by ilaprazole at 5 mg bid, furazolidone at 100 mg bid and levofloxacin at 500 mg qid for the next five days. Four to six weeks after the end of treatment, a 14C-urea breath test was performed for all the subjects to confirm the eradication of H. pylori. The intention-to-treat and per-protocol eradication rates were determined. RESULTS: A total of 190 of the 200 patients completed the study. All 200 patients were included in the intention-to-treat analysis, whereas 190 patients were included in the per-protocol analysis. In the intention-to-treat analysis, the rates of H. pylori eradication in Groups A and B were 85.15% (86/101) and 81.82% (81/99), respectively. In the per-protocol analysis, the H. pylori eradication rates in Groups A and B were 88.66% (86/97) and 87.09% (81/93), respectively. No significant difference was observed (χ(2) = 0.109, P = 0.741) in the eradication rate between Groups A and B. The rates of adverse effects observed in the groups were similar at 6.19% (6/97) for Group A and 7.53% (7/93) for Group B (P > 0.05). No mortality or major morbidities were observed in any of the patients. Symptomatic improvements in the presentation of stomachache, acid regurgitation, and burning sensation were not significantly different between the two groups. CONCLUSION: Ilaprazole-based 10-d standard quadruple therapy does not offer an incremental benefit over modified sequential therapy for the treatment of H. pylori infection, as both treatment regimens appear to be effective, safe, and well-tolerated as initial treatment options.

Enhanced Osteogenic Behavior of ADSCs Produced by Deproteinized Antler Cancellous Bone and Evidence for Involvement of ERK Signaling Pathway.

Calcinated antler cancellous bone (CACB) is useful in repair of bone defects, as its composition and architecture is analogous to natural extracellular bone matrix. The use of CACB scaffolds with adipose-derived stem cells (ADSCs) in repair of rabbit mandibular bone defects was investigated along with the underlying molecular signaling pathways involved. CACB promoted the adhesion, spreading, and viability of ADSCs. Increased extracellular matrix production and expression of osteogenic markers in ADSCs were observed when seeded in CACB. The temporal kinetics of mRNA expression of ADSCs cultured in CACB lagged in comparison with that observed in cells grown in medium with osteogenic supplements. Activation of the extracellular signal-related kinases (ERK) 1/2 and RUNX-2 in CACB-cultured ADSCs was observed, and this activation was attenuated by the MeK inhibitor U0126. Microcomputed tomography scanning analysis and histological evaluations showed that loading the CACB with ADSCs resulted in enhanced new bone formation and angiogenesis when the composites were implanted in rabbit mandibular defects. These results indicated that the osteogenic behavior of ADSCs might be driven by the microenvironment formed by CACB via the ERK signaling pathway. These CACB/ADSCs composites have promising therapeutic potential for large bone defect repairs.

Estrogen regulation of duodenal bicarbonate secretion and sex-specific protection of human duodenum.

BACKGROUND & AIMS: The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer. METHODS: We performed an epidemiologic study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen-receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses. RESULTS: Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20-49 y), who were 3.91- to 5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to 1.32-fold or less among subjects aged 60 years or older. Premenopausal (20-29 y), but not postmenopausal (60-69 y), women had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20-29 y) were significantly higher than in postmenopausal women (60-69 y), whereas there were no significant differences in basal or acid-stimulated DBS between men who were aged 20-29 years or 60-69 years. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17ß-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors α and ß were detected on plasma membranes and in the cytosol of human duodenal epithelial cells. CONCLUSIONS: Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in the prevalence of duodenal ulcer.