African swine fever virus pS273R antagonizes stress granule formation by cleaving the nucleating protein G3BP1 to facilitate viral replication.

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs are regulated by different stimulators including viral infection, which is involved in the antiviral activity of host cells to limit viral propagation. To survive, several viruses have been reported to execute various strategies, such as modulating SG formation, to create optimal surroundings for viral replication. African swine fever virus (ASFV) is one of the most notorious pathogens in the global pig industry. However, the interplay between ASFV infection and SG formation remains largely unknown. In this study, we found that ASFV infection inhibited SG formation. Through SG inhibitory screening, we found that several ASFV-encoded proteins are involved in inhibition of SG formation. Among them, an ASFV S273R protein (pS273R), the only cysteine protease encoded by the ASFV genome, significantly affected SG formation. ASFV pS273R interacted with G3BP1 (Ras-GTPase-activating protein [SH3 domain] binding protein 1), a vital nucleating protein of SG formation. Furthermore, we found that ASFV pS273R cleaved G3BP1 at the G140-F141 to produce two fragments (G3BP1-N1-140 and G3BP1-C141-456). Interestingly, both the pS273R-cleaved fragments of G3BP1 lost the ability to induce SG formation and antiviral activity. Taken together, our finding reveals that the proteolytic cleavage of G3BP1 by ASFV pS273R is a novel mechanism by which ASFV counteracts host stress and innate antiviral responses.

Coreceptor AXL Facilitates African Swine Fever Virus Entry via Apoptotic Mimicry.

African swine fever (ASF) is an acute and hemorrhagic infectious disease caused by African swine fever virus (ASFV), which is listed as an animal epidemic disease that must be reported by The World Organization for Animal Health and that causes serious economic losses to China and even the whole world. Currently, the entry mechanism of ASFV is not fully understood. Especially in the early stages of virus entry, the host factors required for ASFV entry have not yet been identified and characterized. In this study, we demonstrated that ASFV externalized phosphatidylserine (PS) on the envelope functioned as viral apoptotic mimicry, which interacts with AXL, a tyrosine kinase receptor, to mediate ASFV entry into porcine alveolar macrophages (PAMs). We found that AXL was the most pronounced phosphatidylserine receptor (PSR) affecting ASFV entry in PAMs by RNA interference screening. Knockout AXL gene expression remarkably decreased ASFV internalization and replication in MA104 cells. Furthermore, the antibody against AXL extracellular domains effectively inhibited the ASFV entry. Consistent with these results, the deletion of the intracellular kinase domain of AXL and the treatment of the AXL inhibitor, R428, significantly inhibited the internalization of ASFV. Mechanistically, AXL facilitated the internalization of ASFV virions via macropinocytosis. Collectively, we provide evidence that AXL is a coreceptor for ASFV entry into PAMs, which expands our knowledge of ASFV entry and provides a theoretical basis for identifying new antiviral targets. IMPORTANCE African swine fever (ASF) is a highly contagious infectious disease caused by the ASF virus (ASFV), with a mortality rate of up to 100%. ASFV has caused huge economic losses to pig farming worldwide. Specific cellular surface receptors are considered crucial determinants of ASFV tropism. However, the host factors required for ASFV entry have not yet been identified, and the molecular mechanism of its entry remains unclear. Here, we found that ASFV utilized phosphatidylserine (PS) on the surface of virions to masquerade as apoptotic mimicry and facilitated virus entry by interacting with host factor AXL. We found that knockout of AXL remarkably decreased ASFV internalization and replication. The antibody against AXL extracellular domains and AXL inhibitor R428 significantly inhibited the internalization of ASFV via macropinocytosis. The current work deepens our understanding of ASFV entry and provides clues for the development of antiviral drugs to control ASFV infection.

Mesenchymal stem cells-derived IL-6 promotes invasion and metastasis of oral squamous cell carcinoma via JAK-STAT3 signalling.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is often diagnosed with cervical lymph node metastasis. Mesenchymal stem cells (MSCs) and interleukin-6 (IL-6) signalling are considered to play important roles in promoting tumour malignancy. The detailed biological interaction of MSCs and IL-6 and the subsequent effect on OSCC metastasis remain largely unclear. This study aimed to determine the effects and molecular mechanism of MSCs-derived IL-6 on tumour invasion and metastasis. SUBJECTS AND METHODS: The effects of MSC-derived IL-6 and tocilizumab on the proliferation, mobility, and epithelial-mesenchymal transition (EMT) of OSCC cells and potential pathways were detected in vitro. In addition, a murine xenograft model was generated to verify the biological mechanism in vivo. RESULTS: The results showed that the expression of MSCs and EMT-related signals was increased in poorly differentiated OSCC tissues. MSCs released a higher level of IL-6 and promoted the proliferation, invasion, and metastasis of OSCC cells and solid neoplasms, which were activated by the downstream molecules JAK and STAT3. CONCLUSIONS: The results indicated that MSCs-derived IL-6-promoted tumour invasion and metastasis via JAK-STAT3 signalling. Blockade of this pathway by tocilizumab may be a potential treatment to improve the prognosis and survival rate of patients with OSCC.

Influence of oral comprehensive nursing intervention on mechanically ventilated patients in ICU: a randimized controlled study.

OBJECTIVE: To explore the effect of oral comprehensive nursing intervention on mechanically ventilated patients in ICU. METHODS: Select 76 cases of mechanically ventilated patients in severe ICU admitted to our hospital from January 2022 to October 2022 as the research objects, and divide them into the control group and the observation group according to the way the patients receive oral care. 38 cases each. The patients in the control group received routine nursing intervention, and the patients in the observation group received comprehensive oral nursing intervention on the basis of the nursing of the control group. The clinical index data, oropharyngeal hygiene, pH value, blood gas analysis index levels, and the occurrence and death of ventilator-associated pneumonia were compared between the two groups of patients. RESULTS: The hospitalization time of the two groups was compared (P > 0.05); the mechanical ventilation time and ICU stay time of the observation group were significantly lower than those of the control group (all, P < 0.05); the oral odor scores, The plaque index and soft scale index were significantly lower than those of the control group (all, P < 0.05); the pH value, PaO 2 value, and SpO 2 value of the observation group were significantly lower than those of the control group, and the PaCO 2 value was significantly higher than that of the control group. group (all, P < 0.05); the incidence of VAP in the control group was 55.26%, and the mortality rate was 15.79%, the incidence rate of VAP in the observation group was 21.05%, and the mortality rate was 2.63%, and the incidence rate and mortality rate of VAP in the observation group were significantly lower in the control group (all, P < 0.05). CONCLUSION: The application of nursing intervention can effectively promote the recovery of patients, improve the hygiene of patients' oropharynx, adjust the levels of pH and blood gas-related indicators in patients, and reduce VAP in patients. risk of morbidity and mortality.

Oral reactive capillary hemangiomas induced by SHR-1210 in the treatment of non-small cell lung cancer: a case report and literature review.

BACKGROUND: Antibodies to PD-1 and PD-L1 have remarkably improved the overall survival of many patients with advanced solid tumors. SHR-1210 is an anti-PD-1 monoclonal antibody. Dermatologic reactive capillary hemangiomas (RCH) were the most common and unique drug-related AEs of SHR-1210, but rare on oral mucosa and gastrointestinal mucosa. Herein we report a case of RCH occurred in oral mucosa during the clinical trials of SHR-1210 in the treatment of non-small cell lung cancer. CASE PRESENTATION: A male in his 60 s with a history of non-small cell lung cancer received injection of anti-PD-1 monoclonal antibodies SHR-1210. The patient developed drug-related RCH on skin after the first injection and began to have gingival hyperplasia one year after the first injection which gradually increased in size and affect eating and speaking. Anti-PD-1 treatments were continued. After periodontal treatment, two oral lesions and one skin lesion were surgically removed. Similar histological manifestation was found in all three lesions as reactive capillary hemangiomas. All lesions had a good prognosis without recurrence on oral mucosa within one year after surgery. CONCLUSIONS: Oral reactive capillary hemangiomas could be induced by SHR-1210 in the treatment of non-small cell lung cancer. Surgical resection is an effective treatment with a good prognosis.

Clinical diagnosis of oral erosive and ulcerative diseases in children.

Mucosal disease is one of the most common oral cavity diseases in children, among which mucosal erosion and ulceration account for about 50%. Oral mucosal erosion and ulcer diseases in children are mostly acute with obvious pain, affecting speech, eating and swallowing. Some oral mucosal diseases are caused by infection and would result in epidemic among children. The onset age, sites, lesions size and quantity could vary, and some would have recurrence. The detailed medical history and comprehensive physical examination are necessary, some diseases can be diagnosed according to the medical history and clinical manifestations. If diagnosis can not be made, biopsy, blood test and immunofluorescence staining, immunohistochemistry, molecular biology detection, gene diagnosis, tuberculin test and other tests should be considered, and further investigation of systemic diseases should also be carried out if necessary. In some cases, multidisciplinary consultation should be sought. For those who still have no abnormal findings, therapeutic diagnosis can be tried out or secondary biopsy should be performed. In this article, the research progress of oral mucosal diseases in children is reviewed and our own clinical experiences of oral erosive and ulcerative diseases in children are summarized.

Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin.

Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor-promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC-conditioned media (MSC-CM) showed that MSC-CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC-CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N-cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN-mediated PI3K/Akt/mTOR activation.

Long noncoding RNA LINC01133 inhibits oral squamous cell carcinoma metastasis through a feedback regulation loop with GDF15.

BACKGROUND AND OBJECTIVES: Long noncoding RNAs (lncRNAs) play key roles in carcinoma metastasis. We aimed to investigate lncRNA LINC01133 in oral squamous cell carcinoma (OSCC) metastasis. METHODS: The RNA levels of LINC01133 and growth and differentiation factor 15 (GDF15) in tissue samples from OSCC patients, and OSCC cell lines were tested by real-time quantitative polymerase chain reaction (RT-qPCR). SPSS20.0 was used to perform statistical analysis of LINC01133 expression in clinical samples and correlate expression of LINC01133 and GDF15. Cell migration/invasion was assessed via transwell assays. Downstream genes of LINC01133 were screened using RNA-seq and validated by RT-qPCR. GDF15 protein levels were evaluated via Western blot analysis. RESULTS: LINC01133 was downregulated in OSCCs; higher expression of LINC01133 in OSCCs was correlated with less metastasis and better prognosis. LINC01133 inhibited OSCC cell migration and invasion. RNA-seq data showed that LINC01133 inhibited GDF15, and GDF15 could rescue inhibition of OSCC cell migration and invasion caused by LINC01133. Interestingly, GDF15 also inhibited LINC01133. Furthermore, a significant negative correlation between expression of LINC01133 and GDF15 was validated in the clinical study. CONCLUSIONS: Collectively, these data indicate that LINC01133 inhibited OSCC metastasis via a feedback regulation loop of reciprocal inhibition with GDF15, suggesting a new diagnostic and therapeutic target for OSCC.

Efficacy and safety of probiotics in the treatment of Candida-associated stomatitis.

This study aimed at evaluating the short-term efficacy and safety of probiotics as an aid in the treatment of Candida-associated stomatitis in a randomised controlled trial. A total of 65 patients were randomly assigned to receive oral local antifungal agents alone (gargle 2% sodium bicarbonate solution for 30 s, wait 10 min and then apply 2% nystatin paste) or these agents plus local probiotics (the mixture of Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus) three times per day for 4 weeks. Parameters related to hyperaemia, visual analogue scale scores, culture of resting saliva and a lingual dorsum swab and adverse reactions were assessed or recorded in the beginning, middle and end of treatment. Although the baseline characteristics of the participants were similar, both groups showed a significant reduction in pain level and hyperaemia on the tongue mucosa (P = 0.000) after 4-week application. However, despite the reduction in hyperaemia in the probiotic group, these improvements did not display statistically significant differences. The detection rate of Candida spp. was 100% before treatment and 8.21% in the experimental group and 34.6% in the control group after treatment. The detection rate of Candida spp. decreased (P = 0.000) in both groups and was significantly lower in the probiotic group than the control group (P = 0.038). Other analysed micro-organisms, including the decreased detection rate for Lactobacillus spp. (P = 0.049) and the increased detection rate for Staphylococcus epidermidis (P = 0.019), did not display consistent change trends in the probiotics group. Compared with conventional antifungal therapies for oral candidiasis, the inclusion of locally administered probiotics helped improve certain clinical conditions and reduced the prevalence of Candida spp., although the impact of probiotics on oral bacterial species remains to be further studied.

Deep learning algorithms for classification and detection of recurrent aphthous ulcerations using oral clinical photographic images.

Background/purpose: The application of artificial intelligence diagnosis based on deep learning in the medical field has been widely accepted. We aimed to evaluate convolutional neural networks (CNNs) for automated classification and detection of recurrent aphthous ulcerations (RAU), normal oral mucosa, and other common oral mucosal diseases in clinical oral photographs. Materials and methods: The study included 785 clinical oral photographs, which was divided into 251 images of RAU, 271 images of the normal oral mucosa, and 263 images of other common oral mucosal diseases. Four and three CNN models were used for the classification and detection tasks, respectively. 628 images were randomly selected as training data. In addition, 78 and 79 images were assigned as validating and testing data. Main outcome measures included precision, recall, F1, specificity, sensitivity and area under the receiver operating characteristics curve (AUC). Results: In the classification task, the Pretrained ResNet50 model had the best performance with a precision of 92.86%, a recall of 91.84%, an F1 score of 92.24%, a specificity of 96.41%, a sensitivity of 91.84% and an AUC of 98.95%. In the detection task, the Pretrained YOLOV5 model had the best performance with a precision of 98.70%, a recall of 79.51%, an F1 score of 88.07% and an AUC of Precision-Recall curve 90.89%. Conclusion: The Pretrained ResNet50 and the Pretrained YOLOV5 algorithms were shown to have superior performance and acceptable potential in the classification and detection of RAU lesions based on non-invasive oral images, which may prove useful in clinical practice.

Identification of several African swine fever virus replication inhibitors by screening of a library of FDA-approved drugs.

African swine fever (ASF) caused by African swine fever virus (ASFV) is a highly infectious and lethal swine disease. Currently, there is only one novel approved vaccine and no antiviral drugs for ASFV. In the study, a high-throughput screening of an FDA-approved drug library was performed to identify several drugs against ASFV infection in primary porcine alveolar macrophages. Triapine and cytarabine hydrochloride were identified as ASFV infection inhibitors in a dose-dependent manner. The two drugs executed their antiviral activity during the replication stage of ASFV. Furthermore, molecular docking studies showed that triapine might interact with the active center Fe2+ in the small subunit of ASFV ribonucleotide reductase while cytarabine hydrochloride metabolite might interact with three residues (Arg589, Lys593, and Lys631) of ASFV DNA polymerase to block new DNA chain extension. Taken together, our results suggest that triapine and cytarabine hydrochloride displayed significant antiviral activity against ASFV in vitro.

Diagnostic strategies for diseases with fever in dental clinics. / å£è ”å‘çƒ­ç–¾ç— è¾¨æžç­–ç•¥.

Fever is an increase in body temperature beyond the normal range, acting as a protective inflammatory mechanism. This article summarizes diseases with fever encountered in dental clinics, including what is known about pyrexia in coronavirus infection, and further proposes a "six steps in one" identification and analysis strategy to guide the clinical work of stomatology.

Spatial distribution and potential ecological risk assessment of heavy metals in the sediments of fishing ports along the coasts of the Yellow Sea and Bohai Sea.

More than 1,154 fishing ports are widely distributed in China's coastal areas. To date, however, few studies on the pollution and ecological risks of heavy metals in these fishing ports have been reported. In this study, the heavy metals of 148 sediment samples collected from 37 fishing ports along the coasts of the Yellow Sea and Bohai Sea were detected. The results showed that the average contents of Cu, Pb, Zn, and Cd were 53.58 ± 44.53, 27.90 ± 18.10, 143.52 ± 74.72 and 0.28 ± 0.15 mg/kg, respectively. Based on the geoaccumulation index (Igeo) and the potential ecological risk index (RI), we found that fishing ports were the most severely polluted by Cu, but Cd had the highest ecological risk, and most of fishing ports were in moderate potential ecological risk. The positive correlation between heavy metals and total organic carbon indicated that heavy metals in fishing ports were mainly affected by anthropogenic activities.

CD1d facilitates African swine fever virus entry into the host cells via clathrin-mediated endocytosis.

African swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease with high morbidity and mortality in domestic pigs and wild boars. The disease has become a global threat to the pig production industry and has caused enormous economic losses in many countries in recent years. However, the molecular mechanism underlying ASF virus (ASFV) entry of the host cells is not fully understood, which restricts the development of vaccines and antiviral-drugs of ASFV. In this study, we found that the host protein CD1d acts as a host factor, which mediates ASFV entry into the host cells. As the main capsid protein on the surface of ASFV virions, p72 can mediate viral entry. Using IP-MS assay, CD1d was identified as a binding partner of p72 on surface of ASFV virions. Knockdown of CD1d expression and blocking the cells with anti-pCD1d antibody, or incubating ASFV virions with soluble CD1d protein could significantly inhibit ASFV infection. CD1d is located on the membrane surface of primary porcine alveolar macrophages (PAMs) and mediates the virus entry via binding to p72. CD1d knockout or CD1d knockdown assay showed that CD1d could facilitate ASFV virions internalization via clathrin-mediated endocytosis (CME). Furthermore, CD1d interacts with EPS15 to mediate ASFV entry via clathrin-mediated endocytosis. Overall, our findings revealed that CD1d is a novel host-entry factor involved in ASFV internalization via the EPS15-clathrin endocytosis axis and a potential target for antiviral intervention.

Radiographic bone volume alteration after jaw cyst enucleation with or without simultaneous bone grafts: A prospective randomized study.

OBJECTIVE: This study was aimed to evaluate bone healing after jaw cyst enucleation with or without bone substitutes by cone beam computed tomography, and to analyze potential influence factors for bone formation as well. MATERIALS AND METHODS: Sixty seven jaw cyst patients were randomly assigned to two groups. Thirty three patients in control group accepted cystectomy without any filling material. The rest 34 bone cavities which filled with xenograft (DBBM, Bio-Oss®) and covered by absorbable membrane (Bio-Gide®) were included in the guided bone regeneration (GBR) group. All patients were examined with cone bean computerized tomography before operation, 3 and 6 months after surgery. Linear regression analysis was applied to evaluate the influence factors of bone healing. RESULTS: There was no significant difference in bone formation rate at 3 months after enucleation, with shrinkage rate (SR) of cystic lesion in control group and GBR group of 26.43 ± 14.98% and 20.78 ± 10.80%, respectively (p > 0.05). Larger shrinkage area in GBR group was detected on postoperative radiographs after 6 months with SR of 60.11 ± 19.23%, when compared to those in patients without filling (6 months SR: 48.63 ± 19.39%, p = 0.018, <0.05). Linear regression analysis showed that cyst size was negatively correlated with bone formation. CONCLUSION: GBR with bovine xenograft and absorbable membrane showed considerable bone regeneration property in the healing of jaw cystic defects after enucleation of radicular cysts. Cyst size showed a suppressive influence on bone formation.

Carcinoma-associated fibroblasts promotes the proliferation of a lingual carcinoma cell line by secreting keratinocyte growth factor.

Carcinoma-associated fibroblasts (CAFs) have been confirmed to play an important role in the occurrence and development of many kinds of tumors. Regarding proliferation as one manifestation of malignance, the objective was to observe the effects of oral CAFs on the proliferation of oral squamous carcinoma cells (OSCC) and to explore the role of keratinocyte growth factor (KGF) in this process. The results showed that oral CAFs secreted a higher level of KGF than oral normal fibroblasts (NFs), and the conditioned medium of CAFs could increase the viability of carcinoma cells and promote more of them into G2 and S phase. However, after blocking with KGF antibody, the viability and cell cycle of Tca8113 cultured with CAFs conditioned medium changed to be similar with NFs control groups. It was concluded that CAFs could promote the proliferation of OSCC through secreting high levels of KGF. These findings support the use of carcinoma-associated fibroblasts as a novel target in anticancer therapy.

Bone marrow mesenchymal stem cells interact with head and neck squamous cell carcinoma cells to promote cancer progression and drug resistance.

Head and neck cancers are often diagnosed at later stages with poor outcomes. Mesenchymal stem cells (MSC) are recruited to primary tumor sites where they can have pro- and antitumorigenic influence. In trying to better understand the dynamics between MSC and cancer cells, we found that head and neck cancer-MSC exposure resulted in mesenchymal features, elevated proliferation rate, and were more motile, like the same cells that fused with MSC. We orthotopically grafted the parental head and neck cancer cells, those fused with MSC, or those exposed to MSC into the tongues of mice. The cancer cells originally incubated with MSC developed larger more aggressive tumors compared to the parental cell line. RNA sequencing analysis revealed the expression of genes associated with drug resistance in the cancer cells exposed to MSC compared to parental cancer cells. Strikingly, MSC exposed cancer cell lines developed paclitaxel resistance that could be maintained up to 30 d after the initial co-incubation period. The secretory profile of the MSC suggested IL-6 to be a potential mediator of epigenetic imprinting on the head and neck cancer cells. When the MSC-imprinted cancer cells were exposed to the demethylation agent, 5-aza-2'deoxycytidine, it restored the expression of the drug resistance genes to that of parental cells. This study demonstrated that the recognized recruitment of MSC to tumors could impart multiple protumorigenic properties including chemotherapy resistance like that observed in the relatively rare event of cancer/MSC cell fusion.

Periodontal inflammation recruits distant metastatic breast cancer cells by increasing myeloid-derived suppressor cells.

Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms. We show that an experimental model of PI in mice can promote lymph node (LN) micrometastasis, as well as head and neck metastasis of 4T1 breast cancer cells, both in early and late stages of cancer progression. The cervical LNs had a greater tumor burden and infiltration of MDSC and M2 macrophages compared with LNs at other sites. Pyroptosis and the resultant IL-1ß production were detected in patients with PI, mirrored in mouse models. Anakinra, IL-1 receptor antagonist, limited metastasis, and MDSC recruitment at early stages of tumor progression, but failed to reverse established metastatic tumors. PI and the resulting production of IL-1ß was found to promote CCL5, CXCL12, CCL2, and CXCL5 expression. These chemokines recruit MDSC and macrophages, finally enabling the generation of a premetastatic niche in the inflammatory site. These findings support the idea that periodontal inflammation promotes metastasis of breast cancer by recruiting MDSC in part by pyroptosis-induced IL-1ß generation and downstream CCL2, CCL5, and CXCL5 signaling in the early steps of metastasis. These studies define the role for IL-1ß in the metastatic progression of breast cancer and highlight the need to control PI, a pervasive inflammatory condition in older patients.

Inhibitory effects of oral Actinomyces on the proliferation, virulence and biofilm formation of Candida albicans.

OBJECTIVE: The pathogenesis of Candida-associated stomatitis involves the dysfunction of flora antagonistic to Candida. Oral Actinomyces species play an important role in regulating the oral microecological balance. The objective of this study was to investigate the antagonism of three oral Actinomyces against Candida albicans. DESIGN: Suspensions, culture supernatants and bacterial lysates of Actinomyces viscosus, Actinomyces naeslundii and Actinomyces odontolyticus were investigated for their actions upon C. albicans. In addition to a commercial strain, six clinical strains of C. albicans were also tested. The proliferation of C. albicans was assessed using a liquid co-cultivation assay. The adhesion, acid protease and extracellular phospholipase activity, hyphae growth, and biofilm formation of C. albicans were measured. RESULTS: The results showed that the suspensions, culture supernatants and cell lysates of 10(8) colony forming units/ml oral Actinomyces significantly inhibited the proliferation of C. albicans (all P<0.001). The culture supernatants exhibited significant antagonistic interactions in terms of adhesion (A. viscosus P<0.001, A. naeslundii P=0.016 and A. odontolyticus P=0.009), acid protease (A. viscosus P=0.035, A. naeslundii P=0.022, A. odontolyticus P<0.001) and phospholipase activities (A. viscosus P=0.011, A. naeslundii P=0.042, A. odontolyticus P=0.021) of Candida, as well as its hyphae growth (A. viscosus P=0.002, A. naeslundii P=0.008, A. odontolyticus P=0.006). Inhibition of C. albicans biofilm formation was also observed. CONCLUSIONS: This study provides preliminary evidence that oral Actinomyces have inhibitory effects on the proliferation, adhesion, metabolic enzyme activity, hyphae formation and biofilm development of C. albicans.

A systems biology approach identifies effective tumor-stroma common targets for oral squamous cell carcinoma.

The complex interactions between cancer cells and their surrounding stromal microenvironment play important roles in tumor initiation and progression and represent viable targets for therapeutic intervention. Here, we propose a concept of common target perturbation (CTP). CTP acts simultaneously on the same target in both the tumor and its stroma that generates a bilateral disruption for potentially improved cancer therapy. To employ this concept, we designed a systems biology strategy by combining experiment and computation to identify potential common target. Through progressive cycles of identification, TGF-ß receptor III (TßRIII) is found as an epithelial-mesenchymal common target in oral squamous cell carcinoma. Simultaneous perturbation of TßRIII in the oral cancerous epithelial cells and their adjacent carcinoma-associated fibroblasts effectively inhibits tumor growth in vivo, and shows superiority to the unilateral perturbation of TßRIII in either cell type alone. This study indicates the strong potential to identify therapeutic targets by considering cancer cells and their adjacent stroma simultaneously. The CTP concept combined with our common target discovery strategy provides a framework for future targeted cancer combinatorial therapies.