Extracellular vesicles of Bifidobacterium longum reverse the acquired carboplatin resistance in ovarian cancer cells via p53 phosphorylation on Ser15.

We previously found that the relative abundance of Bifidobacterium was increased after chemotherapy; however, the role of Bifidobacterium longum in chemotherapeutic drug resistance in ovarian cancer (OVC) remains unclear. This study aimed to understand the potential effects and mechanism of B. longum extracellular vesicles (B. longum-EVs) on carboplatin (CBP) resistance in OVC. Eight normal and 11 ovarian tissues were collected and the expression of B. longum genomic DNA and its association with acquired CBP resistance in OVC patients was determined. After isolating EVs by ultracentrifugation from B. longum (ATCC 15707), CBP-resistant A2780 cells were treated with PBS, CBP, B. longum-EVs, or CBP + B. longum-EVs, and subsequently analyzed by CCK-8, Edu staining, Annexin V/PI double staining, wound healing, and Transwell assays to detect cell viability, proliferation, apoptosis, migration, and invasion, respectively. MRP1, ATP7A, ATP7B, and p53 expression as well as p53 phosphorylation were measured by western blot analysis. S15A mutation of p53 was assessed to examine the potential role of p53 Ser15 phosphorylation in CBP-resistant OVC. B. longum levels were elevated and positively associated with CBP resistance in OVC patients. Only high concentrations of B. longum-EVs attenuated A2780 cell proliferation, apoptosis, migration, and invasion. B. longum-EVs exposure significantly enhanced the sensitivity of CBP-resistant A2780 cells to CBP and decreased the expression of drug resistance-related proteins. The effect of B. longum-EVs on reversing CBP resistance was completely inhibited by S15A mutation of p53. B. longum-EVs enhanced the sensitivity of OVC cells to CBP through p53 phosphorylation on Ser15.

Machine learning-based dynamic prediction of lateral lymph node metastasis in patients with papillary thyroid cancer.

Objective: To develop a web-based machine learning server to predict lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC) patients. Methods: Clinical data for PTC patients who underwent primary thyroidectomy at our hospital between January 2015 and December 2020, with pathologically confirmed presence or absence of any LLNM finding, were retrospectively reviewed. We built all models from a training set (80%) and assessed them in a test set (20%), using algorithms including decision tree, XGBoost, random forest, support vector machine, neural network, and K-nearest neighbor algorithm. Their performance was measured against a previously established nomogram using area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), precision, recall, accuracy, F1 score, specificity, and sensitivity. Interpretable machine learning was used for identifying potential relationships between variables and LLNM, and a web-based tool was created for use by clinicians. Results: A total of 1135 (62.53%) out of 1815 PTC patients enrolled in this study experienced LLNM episodes. In predicting LLNM, the best algorithm was random forest. In determining feature importance, the AUC reached 0.80, with an accuracy of 0.74, sensitivity of 0.89, and F1 score of 0.81. In addition, DCA showed that random forest held a higher clinical net benefit. Random forest identified tumor size, lymph node microcalcification, age, lymph node size, and tumor location as the most influentials in predicting LLNM. And the website tool is freely accessible at http://43.138.62.202/. Conclusion: The results showed that machine learning can be used to enable accurate prediction for LLNM in PTC patients, and that the web tool allowed for LLNM risk assessment at the individual level.

CD133+ cancer stem-like cells promote migration and invasion of salivary adenoid cystic carcinoma by inducing vasculogenic mimicry formation.

Cancer stem cells (CSCs) have gained much attention due to their roles in the invasion and metastasis of numerous kinds of human cancers. Here, we showed that the positive expression of CD133, the stemness marker, was positively associated with vasculogenic mimicry (VM) formation, local regional recurrence, distant metastasis and poorer prognosis in salivary adenoid cystic carcinoma (ACC) specimens. Compared with CD133- ACC cells, CD133+ cancer stem-like cells had more migration and invasion capabilities, as well as more VM formation. The levels of endothelial cell marker VE-cadherin, MMP-2 and MMP-9 expression in CD133+ cancer stem-like cells and xenograft tumors of nude mice injected with CD133+ cells were significantly higher than those with CD133- cells. The data indicated that CD133+ cancer stem-like cells might contribute to the migration and invasion of ACC through inducing VM formation.

Hyperthermia inhibited the migration of tongue squamous cell carcinoma through TWIST2.

BACKGROUND: Hyperthermia has been shown promising in the treatment of head and neck squamous cell carcinoma (HNSCC); however, the mechanism underlying hyperthermia reducing tumor metastasis is poorly elucidated. TWIST2, an important transcription factor of epithelial-mesenchymal transition (EMT), plays a critical role in the tumor progression and metastasis. The role of TWIST2 in tongue squamous cell carcinoma (TSCC) and its association with hyperthermia still have not been reported. METHOD: The correlations between TWIST2 expression and the clinical-pathologic characteristics of 89 patients with TSCC were evaluated by immunohistochemical staining. TSCC cell lines transfected with siRNA against TWIST2 were heated for 40 min at 42.5°C, and the migration capability of cells was examined by migration assay. Xenograft tumors in nude mice were treated by hyperthermia, and TWIST2 expression was measured. RESULTS: Our data showed that TWIST2 expression was associated with the metastasis of human TSCC. In Tca8113 and Cal-27 cells, TWIST2-siRNA treatment can reduce cell migration ability and has no effect on the cell proliferation and apoptosis. Hyperthermia can decrease the level of TWIST2 in TSCC and inhibit the migration of cells. CONCLUSIONS: This demonstrated that hyperthermia might decrease the migration of Tca8113 and Cal-27 cells by reducing TWIST2 expression. Altogether, these findings suggest an as yet undescribed link between TWIST2 and hyperthermia in TSCC.

C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression.

Epithelial-mesenchymal transition (EMT) is associated with salivary adenoid cystic cancer (ACC) progression and metastasis. Here, we report that ectopic overexpression of c-kit in ACC cell lines is sufficient for acquisition of mesenchymal traits, enhanced cell invasion, along with stem cell properties defined by the presence of a CD133+/CD44+ cell subpopulation. c-kit positively regulated expression of known EMT inducers, also activating TGF-ß to contribute to EMT. c-kit itself was induced by TGF-ß in ACC cell lines and required for TGF-ß-induced EMT. Xenograft experiments showed that c-kit cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in human specimens of ACC, we found that c-kit was abnormally overexpressed and correlated with the prognosis of ACC. Our findings define an important function for c-kit in ACC progression by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease.

A new perspective of vasculogenic mimicry: EMT and cancer stem cells (Review).

Vasculogenic mimicry (VM), a new pattern of tumor microcirculation, is important for the growth and progression of tumors. Epithelial-mesenchymal transition (EMT) is pivotal in malignant tumor progression and VM formation. With increasing knowledge of cancer stem cell (CSC) phenotypes and functions, increasing evidence suggests that CSCs are involved in VM formation. Recent studies have indicated that EMT is relevant to the acquisition and maintenance of stem cell-like characteristics. Thus, in this review we discuss the correlation between CSCs, EMT and VM formation.

[Investigation of infections of soil-transmitted nematodes in Fusheng Village of Poyang Lake area in Jiangxi Province].

OBJECTIVE: To understand the status of soil-transmitted nematode infections in Poyang Lake area in Jiangxi Province. METHODS: The parasitic eggs of stools of residents aged 6-65 years were detected with the Kato-Katz technique in Fusheng Village of Poyang Lake area in Jiangxi Province in 2008. RESULTS: In 2008, the total average infection rate of soil-transmitted nematodes was 37.97%, and the infection rates of Ascarid lumbricoid, Trichuris trichiura and hookworm were 20.39%, 6.67% and 18.45%, respectively. The total infection rate of soil-transmitted nematodes and the rate ofA. lumbricoid were higher in the female than in the male with a statistically significant difference (P < 0.01). The infection rates of T. trichiura and hookworm in the female were higher than those in the male, but there was no significant difference between them (P > 0.05). The total infection rate of soil-transmitted nematodes and the rate of hookworm in different age groups had a similar change pattern which had an increasing trend with the age growing. The infection rate ofA. lumbricoid was the lowest in the age group of 10-19 years and was the highest in the age group of 20-29 years, and then the rate showed a gradually declining trend with the age increasing. The infection rate of T. trichiura had a decreasing trend as the age grew with 2 peaks in the age groups of 10-19 and 40-49, respectively. CONCLUSIONS: The infection rates of soil-transmitted nematodes in population of Fusheng Village in Jiangxi Province are still high. The effective control measures include health education, regular anthelminthic treatment, innoxiously processing of stool and environment reform, and the interruption of the transmitting chain is the fundamental strategy.

[Effect of health education on prevention from schistosome infection in engineering construction workers in Poyang Lake area].

OBJECTIVE: To evaluate the effect of health education on prevention from schistosome infection in engineering construction workers in Poyang Lake area. METHODS: The workers for constructing "De Chang" highway in Poyang Lake area were divided randomly into an experiment group and a control group, "health education + protective skill training" was carried out in the experiment group, whereas, no intervention was implemented in the control group. RESULTS: In the experiment group, the awareness rates of schistosomiasis control knowledge were 7.96% and 96.39% before and after the intervention, respectively; the rates of contacting infested water were 100% and 1.77% pre- and post-intervention, respectively; the work protective rates increased from zero before the intervention to 100% after the intervention; there was no person infected with schistosome after the intervention. However, in the control group, all the indexes above-mentioned had no significant changes. CONCLUSION: The intervention model "health education + protective skill training", can effectively prevent from schistosome infection in engineering construction workers in Poyang Lake area.

[Evaluation on medium-term effect of schistosomiasis comprehensive control strategy based on infectious source control in Poyang Lake area].

OBJECTIVE: To evaluate the medium-term effect and stability of the schistosomiasis comprehensive control strategy based on infectious source control after its popularization and application in marshland endemic areas. METHODS: The schistosomiasis comprehensive control strategy based on infectious source control including "replacing buffalo with machine", "marshlands isolation and grazing forbidden", etc. was implemented in all villages of Sanli Township, a heavy endemic area with schistosomiasis in Jianxian County. The infection situation of schistosomiasis in population and Oncomelania snails in 4 villages around the lake were monitored regularly for 6 consecutive years. RESULTS: The infection rate of schistosomiasis in population significantly decreased after the comprehensive control measures were carried out. Two years later, the infection rate in Huangjia Village was 0, and was sustained at zero for 5 consecutive years; the infection rate in Fengfu Village decreased by 77.24% and stabilized to zero for the next three years; the population infection rates in Fanrong Village and Caomen Village decreased by 82.33% and 82.53%, respectively, then the infection rates of the two villages kept under 1% and were 0 for 2 years and 1 year, respectively. The number of spots with infected snails in two marshlands in pilot areas decreased yearly from 10 before the intervention to 0, in which, the infection rate of snails and the number of spots with infected snails in Huangjiaoniu Marshland and Goulian Marshland decreased to zero 1 year and 3 years after the strategy was implemented, respectively, and the infected snails were not found in these marshlands in following years. CONCLUSION: Strengthening the management of buffaloes in surrounding areas and utilizing marshland resources is the main measure that can consolidate and expand the medium-term and long-term effect of the schistosomiasis 2.2 comprehensive strategy based on infectious source control.

[Investigation on transmission factors of schistosomiasis after replacement of bovine with machine in Jinxian County].

OBJECTIVE: To understand the changes of transmission factors of schistosomiasis after the control strategy of replacing bovine with machine was implemented in the lake region, so as to provide the evidence for long-effective management in marshlands. METHODS: Two villages, which had carried out the control measure of replacing bovine with machine, were selected as observed villages. The data of endemic situation before and after the replacement were collected and analyzed. The species, activities, and stool distributions of infectious resources were surveyed. RESULTS: After the replacement was implemented in 2005, the densities of infected Oncomelania snails gradually decreased in the marshlands from 2006 to 2008; in 2009 and 2010, the densities of infected snails were both zero. The positive rates of stool examinations of residents in the villages decreased from 11.35% in 2004 to 0 in 2009 and 2010. There was still bovine and pig grazing on most of the marshlands, and 41 wild stools were examined with the negative results. CONCLUSION: After replacing bovine with machine is implemented, the marshlands are cleaned continuously, but there are still a few livestock on the marshlands which need to be managed.

[The effect and influencing factors of schistosomiasis control by forbidding livestock denaturing on marshland with Oncomelania snails].

OBJECTIVE: To evaluate the effect of schistosomiasis control by forbidding livestock denaturing on marshland with Oncomelania snails and to analyse its influencing factors. METHODS: The village of Aiguo, Xinhe, Huangjia, Fanrong, Fengfu and Caomen and its respective nearby marshland, i.e., Aiguoniu, Liulingwei, Huangjianiu, Da, Goulian, and Litouzui, in Jinxian county, Jiangxi province were selected as the pilot areas for implementing the measures of forbidding livestock denaturing on the marshlands with Oncomelania snails during the period of the year 2005 to 2007. A total of 300 residents in each village were randomly chosen for stool examination with the Kato-Katz technique every year. The snail survey was carried out in spring and autumn every year on the marshlands close to the villages with systemic sampling method. The marshlands with a height 16.5 m above the sea level in Futian was selected for snail survey and planting with sesame. The residents aged 20 - 50 years old in Fengfu and Aiguo villages were studied by using questionnaire on the compliance of forbidding livestock pasturing on marshlands with Oncomelania snails. RESULTS: Before implementation of the measures, human infection rate with Schistosoma japonicum was 11.35% (90/793) in Aiguo, 4.00% (12/300) in Xinhe, 4.00% (6/150) in Huangjia, 8.00% (12/150) in Fanrong, 3.17% (4/126) in Fengfu and 6.64% (14/211) in Caomen. After implementation in 2008, human schistsome infection rate in the aforementioned 6 villages was declined to 0.18% (1/551), 0.00% (0/348), 0.00% (0/316), 2.27% (7/308), 1.17% (5/428) and 1.16% (5/430), respectively. Only in Fengfu village the decline of the human prevalence was not significant (χ(2) = 2.4, P = 0.12), while in the other 5 villages, human prevalence rate had been declined significantly (χ(2) = 126.77, P < 0.01; χ(2) = 16.31, P < 0.01; χ(2) = 18.79, P < 0.01; χ(2) = 10.39, P < 0.01; χ(2) = 14.17, P < 0.01, respectively). Infected snails were not found in 5 out of the 6 marshlands close to the villages. Three infected snails were founded in Da marshland because of poor environmental isolation. Before planting, the living snail density was 0.063/0.11 m(2) (34/540), and after planting, the living snail density was 0.0074/0.11 m(2) (4/538), a 88.25% reduction (Z = 12.47, P < 0.01) was recorded through economy crop planting at Futiandaan marshland in 2008. A total of 986 pieces of questionnaire were provided, and 968 valid ones were collected. The results of questionnaire indicate that compliance of forbidding livestock denaturing on marshland with Oncomelania snails in Aiguo and Fengfu villages was 84.38% (216/256) and 75.42% (537/712), respectively. Using logistic regression model, knowledge level on harmfulness of livestock denaturing on marshland with Oncomelania snails, willingness of culture with machine to substitute traditional cattle culture, and willingness of investment to marshland culture development are 3 varieties that affect residents' implementation of forbidding livestock denaturing on marshland with Oncomelania snails. CONCLUSION: The infected snail density and human schistosome infection rate were reduced on the marshlands of well environmental isolation after 2 - 3 years implementation of forbidding livestock denaturing on marshlands with Oncomelania snails. The key influencing factors of forbidding livestock denaturing on marshland with Oncomelania snails are knowledge level on harmfulness of livestock denaturing on the snail infested marshlands, the willingness of machine culture to substitute cattle culture, and the willingness of investment to marshland culture development.