Seasonal human coronavirus humoral responses in AZD1222 (ChaAdOx1 nCoV-19) COVID-19 vaccinated adults reveal limited cross-immunity.

Background: Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now widespread; however, the degree of cross-immunity between SARS-CoV-2 and endemic, seasonal human coronaviruses (HCoVs) remains unclear. Methods: SARS-CoV-2 and HCoV cross-immunity was evaluated in adult participants enrolled in a US sub-study in the phase III, randomized controlled trial (NCT04516746) of AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination for one-year. Anti-HCoV spike-binding antibodies against HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63 were evaluated in participants following study dosing and, in the AZD1222 group, after a non-study third-dose booster. Timing of SARS-CoV-2 seroconversion (assessed via anti-nucleocapsid antibody levels) and incidence of COVID-19 were evaluated in those who received AZD1222 primary-series by baseline anti-HCoV titers. Results: We evaluated 2,020/21,634 participants in the AZD1222 group and 1,007/10,816 in the placebo group. At the one-year data cutoff (March 11, 2022) mean duration of follow up was 230.9 (SD: 106.36, range: 1-325) and 94.3 (74.12, 1-321) days for participants in the AZD1222 (n = 1,940) and placebo (n = 962) groups, respectively. We observed little elevation in anti-HCoV humoral titers post study-dosing or post-boosting, nor evidence of waning over time. The occurrence and timing of SARS-CoV-2 seroconversion and incidence of COVID-19 were not largely impacted by baseline anti-HCoV titers. Conclusion: We found limited evidence for cross-immunity between SARS-CoV-2 and HCoVs following AZD1222 primary series and booster vaccination. Susceptibility to future emergence of novel coronaviruses will likely persist despite a high prevalence of SARS-CoV-2 immunity in global populations.

Porphyromonas gingivalis as a promotor in the development of the alcoholic liver disease via ferroptosis.

Alcoholic liver disease (ALD) is a liver disease caused by heavy drinking. Porphyromonas gingivalis (P.g), a major cause of periodontitis, whose antibodies are elevated in severe ALD patients in the plasma. The purpose of this study is to further study the role and the molecular mechanism of P.g in the progress of ALD. In this study, saliva of patients with ALD was collected. Then, an animal model of ALD with oral P.g administration was established, pathology of liver and spleen, intestinal microorganisms and metabolites were analyzed. The molecular mechanism of P.g on ALD was analyzed in vitro. ALD and intestinal microflora and metabolite changes were observed more serious in the alcohol and P.g groups than the alcohol group. Moreover, ferroptosis was aggravated by P.g in the liver. Meanwhile, P.g promoted ferroptosis accomplication with alcohol in vitro, which can be reversed by ferroptosis inhibitors. In conclusion, P.g aggravates ALD through exacerbation gut microbial metabolic disorder in mice with alcohol, which maybe depend on ferroptosis activation in hepatocytes. The study provides a new strategy for prevention and treatment of ALD by improving the oral micro-environment.

Porphyromonas gingivalis triggers inflammation in hepatocyte depend on ferroptosis via activating the NF-κB signaling pathway.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive fat deposition in hepatocytes caused by non-alcoholic liver injury. Porphyromonas gingivalis (P.g) is the main pathogen causing periodontitis, which can aggravate the progression of NAFLD in our previously study. The objective of this study was to further investigate the pathogenesis and moleculer michanisma of NAFLD aggravated by P.g. METHODS: A mouse model of NAFLD was established, and the changes of inflammatory factors and NF-κB signaling pathway in liver tissue and L-02 cells were analyzed by transcriptome sequencing, Western blot, IHC and RT-PCR. In addition, the NF-κB signaling pathway inhibitor QNZ and ferroptosis inhibitor Fer-1 were used to analyze the relationship between NF-κB signaling pathway and ferroptosis in vitro. RESULTS: In vivo and in vitro experiments, P.g can induce liver inflammation and activate NF-κB signaling pathway. At the same time, P.g promotes ferroptosis and inflammation in L-02 in vitro. QNZ alleviates ferroptosis and inflammatory activation in L-02. Fer-1 can relieve the L-02 inflammation caused by P.g products. CONCLUSION: Porphyromonas gingivalis can induce ferroptosis and inflammation in hepatocytes and further worsen liver lesions. The mechanism of ferroptosis in hepatocytes depends on NF-κB signaling pathway, which provides a new strategy for clinical treatment and prevention of NAFLD.

Porphyromonas gingivalis is a risk factor for the development of nonalcoholic fatty liver disease via ferroptosis.

Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that can eventually lead to liver cirrhosis and hepatocellular carcinoma. Porphyromonas gingivalis (P.g) is the main pathogen that causes periodontal disease, which participates in the development of NAFLD. The purpose of our study was to further study the direct role of P.g in NAFLD and the underlying molecular mechanism. An animal model of oral P.g administration was established, and liver function and pathology in this model were evaluated. The gut microbiome and metabolic products were analysed. Furthermore, the Th17/Treg balance in the spleen and liver was assessed. In our study, NAFLD was observed in all the mice that were orally administered P.g. The gut microbiome and metabolic products were altered after oral P.g administration. P.g and ferroptosis were observed in the livers of the mice after oral P.g administration. Additionally, ferroptosis was observed in hepatocytes in vitro, but it was reversed by ferroptosis inhibitors. In addition, P.g triggered an imbalance in the Th17/Treg ratio in the liver and spleen in vivo. These findings suggest that oral P.g administration directly induced NAFLD in mice, which may be dependent on the ferroptosis of liver cells that occurs through the Th17/Treg imbalance induced by disordered microbial metabolism. Therefore, improving the periodontal environment is a novel treatment strategy for preventing NAFLD.

Research progress of spontaneous ruptured hepatocellular carcinoma: Systematic review and meta-analysis.

Background: Spontaneously ruptured hepatocellular carcinoma (rHCC) with hemorrhage is characterized by rapid onset and progression. The aim of this systematic review was to explore the current studies on rHCC with hemorrhage and determine the optimum treatment strategy. Method: The PubMed, Web of Science, Embase, and the Cochrane Library databases were searched for studies reporting survival outcomes with comparison between emergency resection (ER) and transarterial embolization following staged hepatectomy (SH) were included by inclusion and exclusion criteria, the perioperative and survival data were statistically summarized using Review Manager 5.3 software. Result: A total of 8 retrospective studies were included, with a total sample size of 556, including 285 (51.3%) in the ER group and 271 (48.7%) in the SH group. The perioperative blood loss and blood transfusion volume in the SH group were less than those in the ER group, and there were no significant differences in the operative time, incidence of complications, mortality and recurrence rate of tumors between the two groups. The 1-, 2-, 3-year overall survival and 1-, 2-, 3-, 5-year disease-free survival of the ER group were not significantly different from those of the SH group, and the 5-year overall survival rate of ER group was lower than that of the SH group (hazard ratios=1.52; 95% confidence intervals: 1.14-2.03, P=0.005). Conclusion: There was no significant difference in the short-term efficacy of ER or SH in the treatment of ruptured HCC, and SH was superior to ER in the long-term survival.

Tocopherol attenuates the oxidative stress of BMSCs by inhibiting ferroptosis through the PI3k/AKT/mTOR pathway.

Oxidative stress can induce bone tissue damage and the occurrence of multiple diseases. As a type of traditional medicine, tocopherol has been reported to have a strong antioxidant effect and contributes to osteogenic differentiation. The purpose of this study was to investigate the protective effect of tocopherol on the oxidative stress of rat bone marrow-derived mesenchymal stem cells (BMSCs) and the underlying mechanisms. By establishing an oxidative stress model in vitro, the cell counting kit-8 (CCK-8), reactive oxygen species (ROS) analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase (ALP) staining, and Alizarin Red staining (ARS) evaluated the effects of tocopherol on the cell viability, intracellular ROS levels, and osteogenic differentiation in BMSCs. In addition, ferroptosis-related markers were examined via Western blot, RT-PCR, and Mito-FerroGreen. Eventually, the PI3K/AKT/mTOR signaling pathway was explored. We found that tocopherol significantly maintained the cell viability, reduced intracellular ROS levels, upregulated the levels of anti-oxidative genes, promoted the levels of osteogenic-related proteins, and the mRNA of BMSCs stimulated by H2O2. More importantly, tocopherol inhibited ferroptosis and upregulated the phosphorylation levels of PI3K, AKT, and mTOR of BMSCs upon H2O2 stimulation. In summary, tocopherol protected BMSCs from oxidative stress damage via the inhibition of ferroptosis through the PI3K/AKT/mTOR pathway.

Evaluation of antibacterial property and biocompatibility of Cu doped TiO2 coated implant prepared by micro-arc oxidation.

In order to enhance osteogenic differentiation and antibacterial property of dental implants, volcano-shaped microporous TiO2 coatings doped with Cu were fabricated via micro-arc oxidation (MAO) on Ti. Cu-doped coating with different mass ratios of Cu were obtained by changing the concentration of copper acetate in the electrolyte. The structure of Cu-TiO2 coatings were systematically investigated. Element Copper was uniformly distributed throughout the coating. Compared with TiO2 coating, the Cu-doped can further improved proliferation of bone mesenchymal stem cells (BMSCs), facilitated osteogenic differentiation. The bacteriostasis experiments demonstrated that Cu-doped TiO2 coating possess excellent antibacterial property against Staphylococcus aureus (S. aureus) and Porphyromonas gingivalis (P. gingivalis).

Quercetin protects rat BMSCs from oxidative stress via ferroptosis.

Quercetin has been shown to have a wide range of beneficial effects, such as anti-inflammation, anti-oxidation and immunomodulation. The study was designed to explore the role and molecular mechanisms of quercetin on the protective effect of bone marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress in vitro. BMSCs were isolated from 4-week-old male Sprague-Dawley rats. Upon H2O2 stimulation in vitro, the effects of quercetin on the proliferation, anti-oxidation and osteogenic differentiation of BMSCs were evaluated by Cell Counting Kit-8, reactive oxygen species analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase staining and alizarin red staining. Additionally, ferroptosis-related markers were examined by WB, RT-PCR and Mito-FerroGreen. Finally, PI3K/AKT/mTOR signaling pathway was explored in these processes. We found that quercetin significantly maintained BMSCs viability upon H2O2 stimulation. Quercetin upregulated protein (ALP, OPN and RUNX2) and mRNA (Alp, Opn, Ocn and Runx2) levels of osteogenic markers, downregulated ROS levels and upregulated antioxidative gene expressions (Nrf2, Cat, Sod-1 and Sod-2) compared with the H2O2 group. The ferroptosis in BMSCs was activated after H2O2 stimulation, and the phosphorylation level of PI3K, AKT and mTOR was upregulated in H2O2-stimulated BMSCs. More importantly, quercetin inhibited ferroptosis and the phosphorylation level of PI3K, AKT and mTOR were downregulated after quercetin treatment. We conclude that quercetin maintained the viability and the osteoblastic differentiation of BMSCs upon H2O2 stimulation, potentially via ferroptosis inhibition by PI3K/AKT/mTOR pathway.

The Function of circRNA-0047604 in Regulating the Tumor Suppressor Gene DACH1 in Breast Cancer.

Breast cancer is the most common cancer among females. Dachshund Homolog 1 (DACH1) gene is regarded as an important tumor suppressor gene in breast cancer which plays an important regulatory role in the development disease progression, particularly in carcinomas. Circular RNAs (circRNAs) and microRNA (miRNA), regarded as a novel group of noncoding RNAs, are always involved in regulating gene expression. In this work, hsa_circ_0047604 expressed lower in breast cancer tissue and played the role of sponge of miR-548o. By this way, hsa_circ_0047604 could upregulate DACH1 to inhibit breast cancer. In conclusion, this study revealed that hsa_circ_0047604 acted as a tumor suppressor and regulated breast cancer progression via hsa_circ_0047604-miR-548o-DACH1 axis, which might provide a therapeutic method for breast cancer.

SPRC Suppresses Experimental Periodontitis by Modulating Th17/Treg Imbalance.

Object: The aims of the study were to explore the protective effects of S-propargyl-cysteine (SPRC) on periodontitis and to determine the underlying mechanisms. Methods: A rat periodontitis model was constructed by injecting LPS and SPRC (0, 25, and 50 mg/kg/d) was administered intraperitoneally. H2S and CSE level were detected. The alveolar bone level was evaluated by micro-CT, HE staining and methylene blue staining analysis. Inflammation-related factors, Treg and Th17 cells were detected by immunohistochemistry, RT-PCR, immunofluorescence, Western blot and flow cytometry. Phosphorylation levels of ERK1/2 and CREB were analysed. Results: The administration of SPRC significantly increased the expression of CSE in the gingival tissue and the concentration of endogenous H2S in the peripheral blood. Simultaneously, SPRC significantly inhibited the resorption of alveolar bone based on the H&E staining, micro-CT and methylene blue staining analysis. Compared with the periodontitis group, the levels of IL-17A, IL-10 were downregulated and IL-6,TGF-ß1 were upregulated in the SPRC groups. In the SPRC group, the percentage of TH17 cells and the expression of ROR-γt were downregulated, while the percentage of Tregs and the expression of Foxp3 were upregulated accompanied with inhibition of phosphorylation ERK1/2 and CREB. Conclusion: SPRC can prevent the progression of periodontitis by regulating the Th17/Treg balance by inhibition of the ERK/CREB signalling pathway.

Sociodemographic factors associated with high-risk human papillomavirus infection.

OBJECTIVE: To determine the prevalence of high-risk (cancer-associated) human papillomavirus (HPV) infection in U.S. women, identify sociodemographic factors associated with infection, and explore the implications for prevention of HPV-related disease in the vaccination era. METHODS: Women aged 14-59 years (n=1,921) participating in the 2003-2004 National Health and Nutrition Examination Survey provided a vaginal swab which was evaluated for 37 HPV types. We determined which sociodemographic characteristics were associated with high-risk HPV, using logistic regression models. RESULTS: High-risk HPV infection was present in 15.6% (95% confidence interval [CI] 12.6-18.6%) of participants, corresponding to a population prevalence of 12,028,293 U.S. women. Women living below the poverty line, compared with those living three or more times above it, were more likely to be positive for high-risk HPV (23% versus 12%, P = .03). Among participants living below the poverty line, only Mexican-American ethnicity (odds ratio [OR] 0.4, 95% CI 0.2-0.9) and unmarried status (OR 3.3, 95% CI 1.2-8.9) were associated with HPV prevalence. In contrast, several factors were associated with HPV among participants living above the poverty line, including black race (OR 1.4, 95% CI 1.0-2.0), income (OR 0.92, 95% CI 0.84-0.99), unmarried status (OR 2.0, 95% CI 1.3-3.0), and age (OR for 22-25 year olds 2.4, 95% CI 1.4-4.0). CONCLUSION: High-risk HPV infection is common in U.S. women, particularly in poor women. Cervical cancer prevention efforts in the vaccination era must ensure that all low-income women have access to preventive services including education, Pap test screening, and HPV vaccines. Otherwise, existing disparities in cervical cancer could worsen.

Urinary symptoms in adolescent females: STI or UTI?

PURPOSE: To determine if urinary symptoms or urinary tract infections (UTI) were associated with sexually transmitted infections (STI) and which history, clinical, and laboratory findings could distinguish these infections in symptomatic women. METHODS: A cross-sectional sample of 296 sexually active females aged 14-22 years attending a hospital-based teen health center or emergency department were recruited. Genitourinary symptoms, medical and sexual history, and urinalysis results were recorded. STI was defined as a vaginal swab positive for Trichomonas vaginalis or urine nucleic acid amplification test positive for Neisseria gonorrheae or Chlamydia trachomatis. A urine culture with >10,000 colonies of a single pathogen was considered a positive UTI. RESULTS: In the full sample, prevalence of UTI and STI were 17% and 33%, respectively. Neither urinary symptoms nor UTI was significantly associated with STI. Further analyses are reported for the 154 (51%) with urinary symptoms: Positive urine leukocytes, more than one partner in the last three months and history of STI predicted STI. Urinalysis results identified four groups: (1) Normal urinalysis-67% had no infection; (2) Positive nitrites or protein-55% had UTI; (3) Positive leukocytes or blood-62% had STI; and (4) Both nitrites/protein and leukocytes/blood positive-28% had STI and 65% had UTI. Those without a documented UTI were more likely to have trichomoniasis than those with a UTI, and 65% of those with sterile pyuria had STI, mainly trichomoniasis or gonorrhea. CONCLUSIONS: Adolescent females with urinary symptoms should be tested for both UTI and STIs. Urinalysis results may be helpful to direct initial therapy.

Pediatricians' intention to administer human papillomavirus vaccine: the role of practice characteristics, knowledge, and attitudes.

PURPOSE: The objective of this study was to examine pediatrician characteristics and attitudes associated with intention to recommend two hypothetical human papillomavirus (HPV) vaccines. METHODS: A survey instrument mailed to a random sample of 1000 pediatricians assessed provider characteristics, HPV knowledge, and attitudes about HPV vaccination. Intention to administer each of two HPV vaccines types (a cervical cancer/genital wart vaccine and a cervical cancer vaccine) to girls and boys of three different ages (11, 14, and 17 years) was assessed. Linear mixed modeling for repeated measures and multivariable linear regression models were performed to identify variables associated with intention to recommend vaccination. RESULTS: The mean age of participants (n = 513) was 42 years and 57% were female. Participants were more likely to recommend vaccination to girls vs. boys and older vs. younger children, and were more likely to recommend a cervical cancer/genital wart vaccine than a cervical cancer vaccine (p < .0001). Variables independently associated with intention to recommend a cervical cancer/genital wart vaccine were: higher estimate of the percentage of sexually active adolescents in one's practice (beta .084, p = .002), number of young adolescents seen weekly (beta 1.300, p = .015), higher HPV knowledge (beta 1.079, p = .015), likelihood of following the recommendations of important individuals and organizations regarding immunization (beta .834, p = .001), and fewer perceived barriers to immunization (beta -.203, p = .001). CONCLUSIONS: Vaccination initiatives directed toward pediatricians that focus on modifiable predictors of intention to vaccinate, such as HPV knowledge and attitudes about vaccination, may facilitate adherence to emerging national immunization guidelines.