Virus-like structures for combination antigen protein mRNA vaccination.

Improved vaccination requires better delivery of antigens and activation of the natural immune response. Here we report a lipid nanoparticle system with the capacity to carry antigens, including mRNA and proteins, which is formed into a virus-like structure by surface decoration with spike proteins, demonstrating application against SARS-CoV-2 variants. The strategy uses S1 protein from Omicron BA.1 on the surface to deliver mRNA of S1 protein from XBB.1. The virus-like particle enables specific augmentation of mRNAs expressed in human respiratory epithelial cells and macrophages via the interaction the surface S1 protein with ACE2 or DC-SIGN receptors. Activation of macrophages and dendritic cells is demonstrated by the same receptor binding. The combination of protein and mRNA increases the antibody response in BALB/c mice compared with mRNA and protein vaccines alone. Our exploration of the mechanism of this robust immunity suggests it might involve cross-presentation to diverse subsets of dendritic cells ranging from activated innate immune signals to adaptive immune signals.

Periodontitis salivary microbiota exacerbates colitis-induced anxiety-like behavior via gut microbiota.

The gut-brain axis is a bidirectional communication system between the gut and central nervous system. Many host-related factors can affect gut microbiota, including oral bacteria, making the brain a vulnerable target via the gut-brain axis. Saliva contains a large number of oral bacteria, and periodontitis, a common oral disease, can change the composition of salivary microbiota. However, the role and mechanism of periodontitis salivary microbiota (PSM) on the gut-brain axis remain unclear. Herein, we investigated the nature and mechanisms of this relationship using the mice with dextran sulfate sodium salt (DSS)-induced anxiety-like behavior. Compared with healthy salivary microbiota, PSM worsened anxiety-like behavior; it significantly reduced the number of normal neurons and activated microglia in DSS mice. Antibiotic treatment eliminated the effect of PSM on anxiety-like behavior, and transplantation of fecal microbiota from PSM-gavaged mice exacerbated anxiety-like behavior. These observations indicated that the anxiety-exacerbating effect of PSM was dependent on the gut microbiota. Moreover, the PSM effect on anxiety-like behavior was not present in non-DSS mice, indicating that DSS treatment was a prerequisite for PSM to exacerbate anxiety. Mechanistically, PSM altered the histidine metabolism in both gut and brain metabolomics. Supplementation of histidine-related metabolites had a similar anxiety-exacerbating effect as that of PSM, suggesting that histidine metabolism may be a critical pathway in this process. Our results demonstrate that PSM can exacerbate colitis-induced anxiety-like behavior by directly affecting the host gut microbiota, emphasizing the importance of oral diseases in the gut-brain axis.

Case report: Low-grade myofibroblastic sarcoma resembling lymphoma on 18F-FDG PET/CT.

Low-grade myofibroblastic sarcoma is a rare malignant tumor that arises from mesenchymal tissue and affects the head (particularly the tongue and oral cavity) and neck. It is characterized by local recurrence, with metastases being uncommon. We present a 72-year-old man who initially complained of a painless and progressive mass in the right inguinal region and came for consultation, and a malignant tumor was suspected based on the clinical and pelvic MRI manifestations. The 18F-FDG PET/CT revealed that the multiple lesions were located in the mediastinum, retroperitoneum, pelvis, and inguinal lymph nodes; hence, lymphoma was considered to be a combination of the symptoms. However, the histology of the ultrasound-guided puncture indicated low-grade myofibroblastic sarcoma. The patient was next administered chemotherapy, but the lesions did not undergo remission.

A metagenome-wide association study of the gut microbiota in recurrent aphthous ulcer and regulation by thalidomide.

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.

Salivary microbiota of periodontitis aggravates bone loss in ovariectomized rats.

The mechanisms underlying the crosstalk between periodontitis and osteoporosis remain unclear. Recently, the gut microbiota has been recognized as a pivotal regulator of bone metabolism, and oral and gut mucosae are microbiologically connected. In this study, we investigated the effects of periodontitis on osteoporosis through the oral-gut axis. The salivary microbiota of patients with periodontitis was collected and then pumped into the intestine of Sprague-Dawley rats via intragastric administration for 2 weeks. An osteoporosis model was established using ovariectomy. Changes in the maxillae and femora were evaluated using microcomputed tomography (micro CT) and HE staining. Intestinal barrier integrity and inflammatory factors were examined using real-time quantitative polymerase chain reaction and immunofluorescence. The gut microbiota was profiled by 16S rRNA gene sequencing. Metabolome profiling of serum was performed using liquid chromatography-mass spectrometry sequencing. Micro CT and HE staining revealed osteoporotic phenotypes in the maxillae and femora of ovariectomized (OVX) rats. Our results confirmed that the salivary microbiota of patients with periodontitis aggravated femoral bone resorption in OVX rats. In addition, intestinal inflammation was exacerbated after periodontitis salivary microbiota gavage in OVX rats. Correlation analysis of microbiota and metabolomics revealed that lipolysis and tryptophan metabolism may be related to the bone loss induced by the salivary microbiota of patients with periodontitis. In conclusion, periodontitis can aggravate long bone loss through the oral-gut axis in OVX rats.

Active Smoking Induces Aberrations in Digestive Tract Microbiota of Rats.

Cigarette smoking could have certain effects on gut microbiota. Some pioneering studies have investigated effects of active smoking on the microbiome in local segments of the digestive tract, while active smoking-induced microbiome alterations in the whole digestive tract have not been fully investigated. Here, we developed a rat model of active smoking and characterized the effects of active smoking on the microbiota within multiple regions along the digestive tract. Blood glucose and some metabolic factors levels, the microbial diversity and composition, relative abundances of taxa, bacterial network correlations and predictive functional profiles were compared between the control group and active smoking group. We found that active smoking induced hyperglycemia and significant reductions in serum insulin and leptin levels. Active smoking induced region-specific shifts in microbiota structure, composition, network correlation and metabolism function along the digestive tract. Our results demonstrated that active smoking resulted in a reduced abundance of some potentially beneficial genera (i.e. Clostridium, Turicibacter) and increased abundance of potentially harmful genera (i.e. Desulfovibrio, Bilophila). Functional prediction suggested that amino acid, lipid, propanoate metabolism function could be impaired and antioxidant activity may be triggered. Active smoking may be an overlooked risk to health through its potential effects on the digestive tract microbiota, which is involved in the cause and severity of an array of chronic diseases.

Retroperitoneal Recurrence of Melanotic Schwannoma on 18F-FDG PET/CT.

ABSTRACT: Melanotic schwannoma is an uncommon nerve sheath neoplasm. Only 10% of melanotic schwannoma are malignant whereas metastases from melanotic schwannoma are much less common. Hereby we present FDG PET/CT findings of recurrent left retroperitoneal melanotic schwannoma with widespread metastases in a 50-year-old man.

Relationship between dietary factors and recurrent aphthous stomatitis in China: a cross-sectional study.

OBJECTIVE: Recurrent aphthous stomatitis (RAS), a common oral mucosal disorder characterized by chronic, inflammatory, and ovoid ulcers, has a complex etiology. The purpose of the study was to investigate the specific dietary factors influencing the prevalence of RAS. METHODS: A total of 754 participants aged 18 to 59 years were enrolled in this descriptive cross-sectional study. An anonymous questionnaire was adopted to investigate the distribution of RAS, dietary factors, self-reported trigger factors, and therapeutic methods. RESULTS: Among all participants, the prevalence rate of RAS was 21.4%. Univariable analysis showed that fruit, dairy products, vegetables, and water, but not fried foods, fermented foods, spicy foods, and eggs, were preventive factors against RAS. After adjusting for age and sex, multivariable regression analysis suggested that fruit (adjusted odds ratio [aOR] = 0.430, 95% confidence interval [CI] = 0.218-0.847) and water (aOR = 0.294, 95% CI = 0.119-0.726) were protective factors against RAS. CONCLUSION: This study found that the consumption of fruit and water was negatively associated with RAS. These results imply a potential adjunctive and complementary role of food in RAS treatment and some feasible means of RAS prevention.

Mechanical Stress Affects Circadian Rhythm in Skeletal Muscle (C2C12 Myoblasts) by Reducing Per/Cry Gene Expression and Increasing Bmal1 Gene Expression.

BACKGROUND Circadian rhythm can modulate normal activity of humans in adapting to daily environment changes. Mechanical stress loading affects skeletal muscle development and bio-functions. This study aimed to investigate the effects of mechanical stress loading on circadian rhythm in skeletal muscle (C2C12 cells) and to explore the associated mechanism. MATERIAL AND METHODS C2C12 myoblasts were cultured and treated with mechanical stress loading. After mechanical stress loading for 6 h,12 h, and 24 h, we observed the C2C12 myoblasts and determined gene transcription and protein expression of Clock genes, including Clock, Bmal1, Per, and Cry using RT-PCR and western blot assay. RESULTS Mechanical stress loading triggered C2C12 cells growing by force direction and enhanced the cell proliferation at 6 h, 12 h, and 24 h. Gene transcription and protein expression of the core Clock-associated molecules, Clock and Bmal1, increased from start of loading to 12 h, and decreased from 12 h to 24 h. Gene transcription and protein expression of core Clock-associated molecules, Cry and Per, decreased in the first 12 h (from 6 h to 12 h) and increased in the last 12 h (from 12 h to 24 h). CONCLUSIONS Our study revealed that mechanical stress loading affected circadian rhythm in skeletal muscle (C2C12 myoblasts) through reducing Per/Cry and enhancing Clock/Bmal1 gene expression. This study provides insights for investigating circadian rhythm and associated bio-functions of humans.

[Study on the efficacy and safety of metronidazole combined with periodontal tissue regeneration in the treatment of periodontitis].

PURPOSE: To explore the efficacy and safety of ornidazole combined with periodontal tissue regeneration in the treatment of periodontitis. METHODS: From March 2018 to March 2019, 100 patients with periodontitis who received treatment in the Stomatological Hospital Affiliated to the School of Medicine of Nanjing University were selected and randomly divided into the regeneration group and combined treatment group with 50 patients in each group. Patients in the regeneration group received periodontal tissue regeneration treatment, while patients in the combined treatment group received ornidazole combined periodontal tissue regeneration treatment. Related periodontal indexes including periodontal probing depth(PPD), periodontal attachment level(PAL), tooth mobility degree(MD) were measured, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (gsh-px) and interleukin 10 (IL-10) and interleukin 4 (IL-4), c-reactive protein(CRP) level and immune globulin level were detected before and after treatment, the therapeutic effects and complications were recorded and compared. SPSS 21.0 software package was used for statistical analysis of the data. RESULTS: After treatment, PPD, PAL and MD levels in the combined treatment groups were significantly lower than those in the regenerative group (P<0.05). Serum MDA level in the combined treatment group was significantly lower than that in the regenerative group, SOD and gsh-px levels were significantly higher than that in the regenerative group(P<0.05). The serum levels of IgA, IgM, IgG, IgE, IL-10, IL-4 and CRP in the combined treatment group were significantly lower than those in the regenerative treatment group (P<0.05). The total effective rate of the combined treatment group was significantly higher than that of the regenerative treatment group, and the incidence of complications was significantly lower than that of the regenerative group(P<0.05). CONCLUSIONS: Ornidazole combined with periodontal tissue regeneration can improve the level of periodontal index, alleviate oxidative stress injury, improve immune function, inhibit inflammation, and has a significant therapeutic effect with high safety.

A HSV1 mutant leads to an attenuated phenotype and induces immunity with a protective effect.

Herpes simplex virus type 1 (HSV1) is a complicated structural agent with a sophisticated transcription process and a high infection rate. A vaccine against HSV1 is urgently needed. As multiple viral-encoded proteins, including structural and nonstructural proteins, contribute to immune response stimulation, an attenuated or deficient HSV1 vaccine may be relatively reliable. Advances in genomic modification technologies provide reliable means of constructing various HSV vaccine candidates. Based on our previous work, an M6 mutant with mutations in the UL7, UL41, LAT, Us3, Us11 and Us12 genes was established. The mutant exhibited low proliferation in cells and an attenuated phenotype in an animal model. Furthermore, in mice and rhesus monkeys, the mutant can induce remarkable serum neutralizing antibody titers and T cell activation and protect against HSV1 challenge by impeding viral replication, dissemination and pathogenesis.

Analysis of the Infection Status of Healthcare Workers in Wuhan During the COVID-19 Outbreak: A Cross-sectional Study.

BACKGROUND: Healthcare workers (HCWs) at the frontline are facing a substantial risk of infection during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: We acquired information and data on general information on and infection and death status of HCWs in Wuhan during the COVID-19 outbreak and completed statistical analyses. RESULTS: We obtained the data on 2457 infected cases among HCWs in Wuhan, China. More than half of the infected individuals were nurses (52.06%), whereas 33.62% of infected cases were doctors and 14.33% of cases were medical staff. In particular, the case infection rate of nurses (2.22%) was remarkably higher than that of doctors (1.92%). Most infected cases among HCWs were female (72.28%). A majority of the infected HCWs (89.26%) came from general hospitals, followed by specialized hospitals (5.70%) and community hospitals (5.05%). The case infection rate of HCWs (2.10%) was dramatically higher than that of non-HCWs (0.43%). The case fatality rate of HCWs (0.69%) was significantly lower than that of non-HCWs (5.30%). CONCLUSIONS: The infection risk of HCWs is clearly higher than that of non-HCWs. HCWs play an essential role in fighting the pandemic. The analysis of the infection status of HCWs is essential to attract enough attention from the public, provide effective suggestions for government agencies, and improve protective measures for HCWs.

EPO could be regulated by HIF-1 and promote osteogenesis and accelerate bone repair.

Bone defects caused by many factors prompt further study of pathological process and restoration methods. This study was aimed to clarify the effect of erythropoietin on the repair of bone defect. We added the designated concentration of rhEPO to endothelial progenitor cells and marrow stromal cells, then detected its osteogenic and angiogenesis effects. The results showed that rhEPO promoted the proliferation of EPC and ST2 by promoting the mitosis without affecting cell apoptosis. The protein and mRNA levels of angiogenesis and osteogenic related factors exhibited higher expressions. Additionally, rhEPO encapsulated in PLGA scaffolds accelerated the new bone formation in rat calvaria bone defect model. Since the centre of bone defect was hypoxia environment, we cultured EPC and ST2 under hypoxia. SiRNA and an inhibitor of HIF-1 were used to interfere HIF-1, then the following changes of VEGF and EPO were detected. The results showed that all the factors were upregulated under the hypoxia environment. The expression of VEGF at protein and mRNA level decreased as HIF-1 was inhibited or interfered from 6 h, while the mRNA expression of EPO from 6 h and changed significantly at protein level from 12 h. Therefore, EPO is a promising factor for further studies.

Focal Autoimmune Pancreatitis Mimicking Pancreatic Cancer on FDG PET/CT Imaging.

Autoimmune pancreatitis generally results in diffuse increased FDG activity throughout the pancreas on PET/CT images. We present a case of focal autoimmune pancreatitis with abnormal FDG activity involving only the pancreatic tail on PET/CT in a 61-year-old man who was provisionally diagnosed as having pancreatic cancer based on the CT findings. The diagnosis of autoimmune pancreatitis was based on pathological examination and elevated serum immunoglobulin G4 level. Following the steroid therapy, the patient was gradually recovered.

Ephrin-B2/Fc promotes proliferation and migration, and suppresses apoptosis in human umbilical vein endothelial cells.

Tumor growth and metastasis are angiogenesis dependent. Angiogenic growth involves endothelial cell proliferation, migration, and invasion. Ephrin-B2 is a ligand for Eph receptor tyrosine kinases and is an important mediator in vascular endothelial growth factor-mediated angiogenesis. However, research offer controversial information regarding effects of ephrin-B2 on vascular endothelial cells. In this paper, proteome analyses showed that ephrin-B2/Fc significantly activates multiple signaling pathways related to cell proliferation, survival, and migration and suppresses apoptosis and cell death. Cytological experiments further confirm that ephrin-B2/Fc stimulates endothelial cell proliferation, triggers dose-dependent migration, and suppresses cell apoptosis. Results demonstrate that soluble dose-dependent ephrinB2 can promote proliferation and migration and inhibit apoptosis of human umbilical vein endothelial cells. These results also suggest that ephrinB2 prevents ischemic disease and can potentially be a new therapeutic target for treating angiogenesis-related diseases and tumors.

18F-FDG PET/CT of Primary Cervical Granulocytic Sarcoma.

Granulocytic sarcoma is an uncommon solid extramedullary tumor composed of immature leukocytes and commonly associated with acute myelogenous leukemia. Isolated granulocytic sarcoma in the cervix of uterus is exceedingly rare. Hereby we describe a case of FDG PET/CT finding of cervical granulocytic sarcoma without acute myelogenous leukemia in a 51-year-old patient.

99Tcm-MDP Imaging of Osteopetrosis: Case Report.

Osteopetrosis, also known as marble bone disease, is a clinically rare genetic disease, which represents a heterogeneous group of rare, inherited bone dysplasias that share the hallmark of abnormally increased bone density caused by osteoclast dysfunction. Hereby, the authors describe a case of osteopetrosis that showed increased diffuse radioactive uptake on whole body bone (99)Tc(m)-methylene diphosphonate imaging in a 56-year-old man, which increased universal radioactive uptake on craniofacial bone imaging, and enlargement of the limb long bone near the joints with evenly symmetrical enriched distribution of radioactivity. Osteopetrosis was made which based on these features and characteristics shown on (99)Tc(m)-MDP imaging.Skeletal scintigraphy with Tc-methylene diphosphonate imaging is helpful to the diagnosis of osteopetrosis. There is a characteristic of osteopetrosis different from other bone metabolic diseases.

FDG PET/CT of neuroendocrine carcinoma of the thyroid gland.

Neuroendocrine carcinoma of the thyroid gland is very rare and difficult to diagnose preoperatively. Hereby we describe a case of neuroendocrine carcinoma of the thyroid that showed intense FDG activity on PET/CT in a 61-year-old woman who had partial thyroidectomy 5 years ago for a suspicious thyroid nodule that was diagnosed as neurofibroma pathologically.

Ultrasensitive determination of DNA sequences by flow injection chemiluminescence using silver ions as labels.

We presented a new strategy for ultrasensitive detection of DNA sequences based on the novel detection probe which was labeled with Ag(+) using metallothionein (MT) as a bridge. The assay relied on a sandwich-type DNA hybridization in which the DNA targets were first hybridized to the captured oligonucleotide probes immobilized on Fe3O4@Au composite magnetic nanoparticles (MNPs), and then the Ag(+)-modified detection probes were used to monitor the presence of the specific DNA targets. After being anchored on the hybrids, Ag(+) was released down through acidic treatment and sensitively determined by a coupling flow injection-chemiluminescent reaction system (Ag(+)-Mn(2+)-K2S2O8-H3PO4-luminol) (FI-CL). The experiment results showed that the CL intensities increased linearly with the concentrations of DNA targets in the range from 10 to 500 pmol L(-1) with a detection limit of 3.3 pmol L(-1). The high sensitivity in this work may be ascribed to the high molar ratio of Ag(+)-MT, the sensitive determination of Ag(+) by the coupling FI-CL reaction system and the perfect magnetic separation based on Fe3O4@Au composite MNPs. Moreover, the proposed strategy exhibited excellent selectivity against the mismatched DNA sequences and could be applied to real samples analysis.

Simultaneous detection of multiple DNA targets based on encoding metal ions.

We present a novel strategy for simultaneous electrochemical detection of multiple DNA targets based on the use of different encoding metal ions as tags. The principle of this scheme is that metal ions bound to metallothionein (MT) molecules can be released down after hybridization with DNA targets and then be detected by stripping voltammetry. The novel detection probes, ssDNA/MT conjugates, covered with different metal ions were synthesized for the first time, then three encoding metal ions (Zn(2+), Cd(2+), and Pb(2+)) were used to differentiate the signals of three virus DNA due to their well-defined anodic stripping peaks at -1.13 V (Zn), -0.78 V (Cd), and -0.52 V (Pb) at BiFE, respectively. The anodic peak currents increased linearly with the concentrations of DNA targets in the range from 0.1 nM to 10nM with a detection limit of 33 pM. In addition, the one-base mismatched target was effectively discriminated from the complementary target. The described results demonstrated that this method possesses high sensitivity and selectivity for multi-target DNA assay and has great potential in applications for detection of even more targets in biological assays, particularly immunoassays.