Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.

Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines.

Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p < 0.001). In the Sf9 cells group, GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses (prototype and diverse variants of concern [VOCs]) increased by 22.23-75.93 folds from baseline to day 28 post-booster, while the CoronaVac group showed increases of only 3.29-10.70 folds. Similarly, neutralizing antibodies against live SARS-CoV-2 viruses (prototype and diverse VOCs) increased by 68.18-192.67 folds on day 14 post-booster compared with the baseline level, significantly greater than the CoronaVac group (19.67-37.67 folds). A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster (mean IFN-γ+ spot-forming cells per 2 × 105 peripheral blood mononuclear cells: 26.66 vs. 13.59). Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group (68.18% vs. 36.59%, p = 0.004). Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine (Sf9 cells) against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern, while causing no apparent safety concerns.

Identification of fecal microbiome signatures associated with familial longevity and candidate metabolites for healthy aging.

Gut microbiota associated with longevity plays an important role in the adaptation to damaging stimuli accumulated during the aging process. The mechanism by which the longevity-associated microbiota protects the senescent host remains unclear, while the metabolites of the gut bacteria are of particular interest. Here, an integrated analysis of untargeted metabolomics and 16S rRNA gene sequencing was used to characterize the metabolite and microbiota profiles of long-lived individuals (aged ≥90 years) in comparison to old-elderly (aged 75-89 years), young-elderly (aged 60-74 years), and young to middle-aged (aged ≤59 years) individuals. This novel study constructed both metabolite and microbiota trajectories across aging in populations from Jiaoling county (the seventh longevity town of the world) in China. We found that the long-lived group exhibited remarkably differential metabolomic signatures, highlighting the existence of metabolic heterogeneity with aging. Importantly, we also discovered that long-lived individuals from the familial longevity cohort harbored a microbiome distinguished from that of the general population. Specifically, we identified that the levels of a candidate metabolite, pinane thromboxane A2 (PTA2), which is positively associated with aging, were consistently higher in individuals with familial longevity and their younger descendants than in those of the general population. Furtherly, functional analysis revealed that PTA2 potentiated the efficiency of microglial phagocytosis of ß-amyloid 40 and enhanced an anti-inflammatory phenotype, indicating a protective role of PTA2 toward host health. Collectively, our results improve the understanding of the role of the gut microbiome in longevity and may facilitate the development of strategies for healthy aging.

Restoration of the Oral Microbiota After Surgery for Head and Neck Squamous Cell Carcinoma Is Associated With Patient Outcomes.

OBJECTIVE: To evaluate the dynamics of the oral microbiome and associated patient outcomes following treatment of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: This was a prospective cohort study at a tertiary academic center in Hong Kong SAR of patients with head and neck squamous cell carcinoma evaluating the oral microbiome in pre- and postsurgery oral rinses (at 1, 3, and 6 months) with 16S rRNA gene V3-V4 amplicon sequencing. RESULTS: In total, 76 HNSCC patients were evaluated. There was a significantly depressed alpha diversities of oral microbial communities observed in HNSCC oral rinse samples within the first 6 months post-surgery when compared to presurgery or healthy controls. Distant clustering between pre- and postsurgery was also observed (p < 0.022). Following treatment, eight oral bacterial genera showed a trend towards the restoration in the relative abundances that approximate healthy persons. In evaluating patient outcomes, the decreased relative abundance of three periodontal bacteria (Capnocytophaga, Prevotella 7, and Leptotrichia) and the increased relative abundance of two commensal bacteria (Streptococcus and Rothia) at 6 months postsurgery compared to presurgery showed a better 3-year disease-specific survival (a cutoff of Kaplan-Meier survival curve test p < 0.3 at 36 months). In particular, the postsurgery restoration of Prevotella 7 was statistically significant in the surveyed patients (survival rate of 84% vs. 56% at 36 months, p = 0.0065). CONCLUSIONS: Oral microbiome dysbiosis associated with HNSCC is dynamic. These dynamics of the oral microbiome postsurgery are also associated with patient treatment and outcomes and may serve as potential biomarkers for patient management in HNSCC.

Exploring the relationship between spiritual well-being and death anxiety in patients with gynecological cancer: a cross-section study.

BACKGROUND: In recent years, spiritual well-being has gradually gained the attention of health care providers in China, especially those in oncology departments, who have recognized the importance of improving spiritual well-being in cancer patients. Since most of the current research on spiritual well-being has been carried out in areas with religious beliefs, this study was conducted in the context of no development of formal religion. The purpose of this study was to explore the relationship between death anxiety and spiritual well-being and the related factors of spiritual well-being among gynecological cancer patients. METHODS: This cross-section study was conducted among 586 gynecological cancer patients. The European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-spiritual well-being32 (EORTC QLQ-SWB32) and Templer's Death Anxiety Scale (T-DAS) were used to measure spiritual well-being and death anxiety. The Multiple Linear Regression Model was used to determine the relationship between spiritual well-being and death anxiety. RESULTS: For all participants, the highest QLQ-SWB32 centesimal score was 75.13 on the Relationship with Other scale, and the lowest was 60.33 on the Relationship with Someone or Something Greater Scale. The mean Death Anxiety score was 5.31 (SD 3.18). We found that Relationship with Someone or Something Greater was the only scale not associated with death anxiety. Overall, patients with lower death anxiety have a higher level of spiritual well-being. Besides, a high Relationship with Other score was associated with living with a partner (B = 2.471, P < 0.001) and married (B = -6.475, P = 0.001). Patients with higher Global-SWB were retired (B = 0.387, P = 0.019). CONCLUSIONS: Our study found that the spiritual well-being of patients with gynecological cancer in China was no worse than in other countries with religious beliefs and patients with lower death anxiety have a higher level of spiritual well-being. Clinical staff should pay attention to the spiritual health of cancer patients, and spiritual care should be regarded as an essential element in cancer care.

The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma.

The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of Fusobacterium and Peptostreptococcus in HNSCC tumor tissues when compared to the adjacent normal tissues, and in HNSCC oral rinses when compared to healthy subjects, while ten other bacterial genera were largely depleted. These HNSCC-related bacteria were discriminative for HNSCC and controls with area under the receiver operating curves (AUCs) of 0.84 and 0.86 in tissue and oral rinse samples, respectively. Moreover, Fusobacterium nucleatum abundance in HNSCC cases was strongly associated with non-smokers, lower tumor stage, lower rate of recurrence, and improved disease-specific survival. An integrative analysis identified that enrichment of F. nucleatum was associated with host gene promoter methylation, including hypermethylation of tumor suppressor genes LXN and SMARCA2, for which gene expressions were downregulated in the HNSCC cohort from The Cancer Genome Atlas. In conclusion, we identified a taxonomically defined microbial consortium associated with HNSCC that may have clinical potential regarding biomarkers for early detection or intervention. Host-microbe interactions between F. nucleatum enrichment and clinical outcomes or host gene methylation imply a potential role of F. nucleatum as a pro-inflammatory driver in initiating HNSCC without traditional risk factors, which warrants further investigation for the underlying mechanisms.

Effects of passive music therapy on anxiety and vital signs in lung cancer patients undergoing peripherally inserted central catheter placement procedure.

PURPOSE: To evaluate the effects of passive music therapy on anxiety and vital signs among lung cancer patients at their first peripherally inserted central catheter placement procedure in China. METHODS: A randomized controlled clinical trial was conducted in the cancer center of a hospital in Chengdu from May to December 2017. A total of 304 lung cancer patients who met the inclusion and exclusion criteria were recruited and randomly assigned to experimental (n = 152) and control (n = 152) group, respectively. The control group only received standard care, while the experimental group received standard care and passive music therapy during peripherally inserted central catheter placement (30-45 min) and after catheterization, until discharged from the hospital (twice a day, 30 min once). Measures include anxiety and vital signs (blood pressure, heart rate, and respiratory rate). RESULTS: Repetitive measurement and analysis of variance showed that the patients in experimental group had a statistically significant decrease in anxiety, diastolic blood pressure, and heart rate over time compared to the control group, but no significant difference was identified in systolic blood pressure and respiratory rate. CONCLUSION: Passive music therapy can efficiently relieve the anxiety of lung cancer patients during peripherally inserted central catheter placement. It also can lower the patient's diastolic blood pressure and slow down the heart rate. So, music therapy benefits patients with peripherally inserted central catheter.

Durable Antimicrobial Behaviour from Silver-Graphene Coated Medical Textile Composites.

Silver nanoparticle (AgNP) and AgNP/reduced graphene oxide (rGO) nanocomposite impregnated medical grade polyviscose textile pads were formed using a facile, surface-mediated wet chemical solution-dipping process, without further annealing. Surfaces were sequentially treated in situ with a sodium borohydride (NaBH4) reducing agent, prior to formation, deposition, and fixation of Ag nanostructures and/or rGO nanosheets throughout porous non-woven (i.e., randomly interwoven) fibrous scaffolds. There was no need for stabilising agent use. The surface morphology of the treated fabrics and the reaction mechanism were characterised by Fourier transform infrared (FTIR) spectra, ultraviolet-visible (UV-Vis) absorption spectra, X-ray diffraction (XRD), Raman spectroscopy, dynamic light scattering (DLS) energy-dispersive X-ray analysis (EDS), and scanning electron microscopic (SEM). XRD and EDS confirmed the presence of pure-phase metallic silver. Variation of reducing agent concentration allowed control over characteristic plasmon absorption of AgNP while SEM imaging, EDS, and DLS confirmed the presence of and dispersion of Ag particles, with smaller agglomerates existing with concurrent rGO use, which also coincided with enhanced AgNP loading. The composites demonstrated potent antimicrobial activity against the clinically relevant gram-negative Escherichia coli (a key causative bacterial agent of healthcare-associated infections; HAIs). The best antibacterial rate achieved for treated substrates was 100% with only a slight decrease (to 90.1%) after 12 equivalent laundering cycles of standard washing. Investigation of silver ion release behaviours through inductively coupled plasmon optical emission spectroscopy (ICP-OES) and laundering durability tests showed that AgNP adhesion was aided by the presence of the rGO host matrix allowing for robust immobilisation of silver nanostructures with relatively high stability, which offered a rapid, convenient, scalable route to conformal NP-decorated and nanocomposite soft matter coatings.

Characterization of Mucosa-Associated Microbiota in Matched Cancer and Non-neoplastic Mucosa From Patients With Colorectal Cancer.

Colonic microbiota play important roles in the development of colorectal cancer. We aim to characterise the mucosa-associated microbiota in the tumour as well as the matched non-neoplastic mucosa from patients with colorectal cancer. Microbiota profiling in these samples was done using high-throughput 16S rRNA amplicon sequencing. Our results showed that the microbiota richness and diversity were similar between the tumour and non-neoplastic mucosae. Linear discriminant analysis effect size (LEfSe) analysis identified Fusobacterium and Campylobacter as the key genera of the tumour while Brevundimonas as the key genus of the non-neoplastic mucosa. In patients with shorter survival period, the relative abundance of Fusobacterium and Campylobacter was significantly higher in the tumour. Besides, regardless of the sites, tumour showed higher abundance of Fusobacterium. On the other hand, the relative abundance of Brevundimonas was significantly lower in the tumour. When validated with quantitative ddPCR, we found the absolute numbers of both Fusobacterium and F. nucleatum were significantly higher in the carcinoma from patients with shorter survival period, conventional type of adenocarcinoma in the distal portion of the large intestine (descending colon, sigmoidal colon, and rectum). In conclusion, our study showed a compositional alteration in the mucosa-associated microbiota in the tumour, which may contribute to the progression of colorectal cancer.

Synergistic antibacterial activity between penicillenols and antibiotics against methicillin-resistant Staphylococcus aureus.

Penicillenol A2 (isolated from deep-sea fungus Penicillium biourgeianum DFFSCS023) has good antibacterial activity against methicillin-sensitive Staphylococcus aureus and in combination with beta-lactam antibiotics it could significantly decrease methicillin-resistant Staphylococcus aureus (MRSA) survival, which provides a novel treatment consideration for MRSA-caused infections.

Synergistic Effects of Salvianolic Acid B and Puerarin on Cerebral Ischemia Reperfusion Injury.

Ischemic stroke (IS) is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. It has been a worldwide critical disease threatening to the health and life of human beings. Despite significant progresses achieved, effective treatment still remains a formidable challenge due to the complexity of the disease. Salvianolic acid B (Sal-B) and Puerarin (Pue) are two active neuroprotectants isolated from traditional Chinese herbs, Salvia miltiorrhiza and Kudzu root respectively, which have been used for the prevention and treatment of IS for thousands of years in China. The activities of two compounds against cerebral ischemia reperfusion injury have been confirmed via various pathways. However, the therapeutic efficacy of any of the two components is still unsatisfied. In the present study, the effect of the combination of Sal-B and Pue on IS was evaluated and validated in vitro and in vivo. The ratio of two compounds was firstly optimized based on the results of CoCl2 damaged PC12 cells model. The co-administration exhibited significantly protective effect in CoCl2 induced PC12 cells injury model by reducing ROS, inhibiting apoptosis and improving mitochondrial membrane potential in vitro. Moreover, Sal-B + Pue significantly relieved neurological deficit scores and infarct area than Sal-B or Pue alone in vivo. The results indicated that neuroprotection mechanism of Sal-B + Pue was related to TLR4/MyD88 and SIRT1 activation signaling pathway to achieve synergistic effect, due to the inhibition of NF-κB transcriptional activity and expression of pro-inflammatory cytokine (TNF-α, IL-1ß, IL-6). In conclusion, the combination of Sal-B and Pue exerted much stronger neuroprotective effect than Sal-B or Pue alone, which provides a potential new drug and has great significance for the treatment of IS.

Differential expression of virulence genes in Legionella pneumophila growing in Acanthamoeba and human monocytes.

Legionella pneumophila, the causative agent of Legionnaires' disease, is widely distributed throughout natural and artificial water systems and can replicate in macrophages and amoebae. Amoebae are the natural hosts of L. pneumophila, whereas macrophages are incidentally infected. The life cycle of L. pneumophila comprises a replicative phase within the Legionella-containing vacuole (LCV) and a transmissive phase during which bacterial cells become motile and are released via killing of the host. Although the host death mechanisms induced by L. pneumophila have been studied, the expression patterns of related L. pneumophila genes have not been reported. The present study compared the expression patterns of host cell death-associated genes in L. pneumophila grown in the human monocytic cell line THP-1 and Acanthamoeba castellanii. Notably, when L. pneumophila was grown in THP-1, expression of the gene flaA, which is involved in the induction of pyroptosis, was downregulated during the course of infection. In contrast, sdhA associated indirectly with host death, was upregulated. Expression of the genes vipD and sidF, which are involved in the induction and suppression of apoptosis, changed by less than 2-fold. Notably, a lower percentage of pyroptotic cells was observed among infected THP-1 cells relative to uninfected cells, and the latter exhibited stronger expression of caspase-1. A different pattern was observed when L. pneumophila was grown in A. castellanii: flaA and vipD were activated, whereas sdhA and sidF were downregulated during the later stage of replication. The percentage of non-viable (annexin-V+ PI+ or annexin-V+PI-) A. castellanii organisms increased with Legionella infection, and the expression of metacaspase-1, which is involved in encystation was up-regulated at late infection time. In summary, L. pneumophila can multiply intracellularly in both amoebae and macrophages to induce cell death and secondary infection, and this characteristic is essential for its survival in water and the lungs. The gene expression profiles observed in this study indicated the increased cytotoxicity of L. pneumophila in A. castellanii, suggesting an increased adaptation of Legionella to this host.

Response Surface Optimized Infrared-Assisted Extraction and UHPLC Determination of Flavonoid Types from Flos Sophorae.

Single-factor experiment and Box-Behnken design were applied to optimize the infrared-assisted extraction (IRAE) of rutin, quercetin, kaempferol, and isorhamnetin from Flos sophorae. Four factors (extract solvent, solid-liquid ration, extraction time, infrared power) affecting the extraction yield of flavonoids were studied. Under optimized conditions the extraction yield was 33.199 ± 0.24 mg/g, which substantially improved, compared with heating reflux extraction (HRE) and ultrasonic-assisted extraction (UAE), while extraction time was only 9 min. The eluents were rich in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azobis (2-methyl-propionamidine) dihydrochloride radical scavenging potential (IC50 of DPPH: 53.44 ± 0.01 µg/mL, oxygen radical absorbance capacity (ORAC): 3785.83 ± 52 µmol/g) than the extracts obtained by HRE and UAE. In addition, an ultra-high performance liquid chromatography method was optimized for the identification and quantification of the tested flavonoids, and the method was validated based on its correlation coefficient (r), reproducibility (RSD, n = 5), and recovery values, which were 0.9994-0.9998, 0.74-1.83%, and 97.78-102.94%, respectively. These results confirmed that high extraction yield of flavonoids results in stronger antioxidant values and response surface methodology optimization of IRAE is a promising alternative to traditional extraction techniques for flavonoids from medicinal plants.

[Knowledge-Attitude-Practice and Associated Factors of Cancer Patients with Peripherally Inserted Central Catheter].

OBJECTIVE: To investigate the Knowledge-Attitude-Practice (KAP) of cancer patients with peripherally inserted central catheter (PICC) and its associated factors. METHODS: A cross-sectional study was undertaken in 650 cancer patients with PICC in the West China Hospital, Sichuan University, from April 2014 to March 2015. Data were collected through a self-designed questionnaire in relation to KAP and its associated factors. RESULTS: A total of 619 valid questionnaires were returned. The participants had an average score of 9.28 +/- 2.04 in knowledge, 27.95 +/- 4.17 in attitude, and 25.67 +/- 4.00 in practice. Occupation was associated with catheter-related knowledge. Comorbidity (with diabetes, hypertension and coronary heart disease) was associated with catheter-related attitudes (P=0.040). Gender (P=0.015) and catheter insertion site (P=0.023) were associated with PICC practice. The multivariable linear regression model showed that female patients (standardized partial regression coefficient = -0.097, P = 0.024) and those with a higher level of education (standardized partial regression coefficient=0.125, P=0.017) had a higher score in PICC practice. CONCLUSION: Overall, a high level of KAP was found in cancer patients with PICC. Clinical nursesshould provide personalized catheter-related education for patients according to their gender and level of education. Special attention should be paid to those with comorbidities such as diabetes mellitus, hypertension, coronary heart disease and other chronic diseases.