The Regulatory Network of hnRNPs Underlying Regulating PKM Alternative Splicing in Tumor Progression.

One of the hallmarks of cancer is metabolic reprogramming in tumor cells, and aerobic glycolysis is the primary mechanism by which glucose is quickly transformed into lactate. As one of the primary rate-limiting enzymes, pyruvate kinase (PK) M is engaged in the last phase of aerobic glycolysis. Alternative splicing is a crucial mechanism for protein diversity, and it promotes PKM precursor mRNA splicing to produce PKM2 dominance, resulting in low PKM1 expression. Specific splicing isoforms are produced in various tissues or illness situations, and the post-translational modifications are linked to numerous disorders, including cancers. hnRNPs are one of the main components of the splicing factor families. However, there have been no comprehensive studies on hnRNPs regulating PKM alternative splicing. Therefore, this review focuses on the regulatory network of hnRNPs on PKM pre-mRNA alternative splicing in tumors and clinical drug research. We elucidate the role of alternative splicing in tumor progression, prognosis, and the potential mechanism of abnormal RNA splicing. We also summarize the drug targets retarding tumorous splicing events, which may be critical to improving the specificity and effectiveness of current therapeutic interventions.

Imbalanced EphB4/EphrinB2 Signaling Modulates Bone Resorption in Periodontitis Induced by Porphyromonas gingivalis.

Periodontitis, a chronic infectious disease in periodontal tissues, is characterized by an imbalance of alveolar bone resorption and remodeling, which eventually results in tooth loosening and even tooth loss. The etiology of periodontitis is polymicrobial synergy and dysbiosis, in which Porphyromonas gingivalis (P. gingivalis) is one of the primary pathogens responsible for periodontitis progression. The interplay of EphrinB2/EphB4 is crucial for osteoblast-osteoclast communication during bone remodeling and healing. This study investigates the mechanism of EphB4/EphrinB2 transduction modulating osteogenesis inhibition and bone resorption in periodontitis induced by P. gingivalis. An in vivo model of chronic periodontitis provoked by P. gingivalis was constructed, the inflammation and bone resorption were evaluated. The expression of EphB4 and EphrinB2 proteins in periodontal tissues was detected, which was also evaluated, respectively, in osteoblasts and osteoclasts infected with P. gingivalis in vitro. Then, a simulated coculture model of osteoblasts and osteoclasts was established to activate the forward and reverse pathways of EphB4/EphrinB2 with P. gingivalis infection. This study showed that P. gingivalis infection promoted alveolar bone resorption in rats and enhanced EphB4 and EphrinB2 expression in periodontal tissues. EphB4 and molecules associated with osteogenesis in osteoblasts infected with P. gingivalis were inhibited, while EphrinB2 and osteoclast differentiation-related markers in osteoclasts were activated. In conclusion, this study suggested that EphB4/EphrinB2 proteins were involved in alveolar bone remodeling in the process of periodontitis induced by P. gingivalis infection. Moreover, attenuated EphB4/EphrinB2 with P. gingivalis infection weakened osteoblast activity and enhanced osteoclast activity.

Minnelide Markedly Reduces Proteinuria in Mice with Adriamycin Nephropathy by Protecting Against Podocyte Injury.

Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children. The current major therapy is hormones for most steroid-sensitive patients. However, many patients have recurrent relapses of the disease and require long-term immunosuppression, leading to significant morbidity due to the side effects of the drugs. Therefore, better drugs need to be urgently explored to treat nephrotic syndrome while avoiding the side effects of drugs. Minnelide, a water-soluble prodrug of triptolide, has been proved to be effective in treating cancers in many clinical trials. This study aimed to investigate the therapeutic effect of minnelide in mice with adriamycin (ADR) nephropathy, its underlying protection mechanisms, and its reproductive toxicity. Minnelide was administered intraperitoneally to 6-8-week female mice with adriamycin nephropathy for 2 weeks, and the urine, blood, and kidney tissues were taken to analyze the therapeutic effect. In addition, we evaluated reproductive toxicity by measuring the levels of gonadal hormones and observing the histological changes in ovaries and testes. Primary mouse podocytes were exposed to puromycin (PAN) to damage the cytoskeleton and induce apoptosis, and then, triptolide was used to evaluate the therapeutic effect and underlying protection mechanisms in vitro. It was observed that minnelide dramatically alleviated proteinuria and apoptosis in mice with adriamycin nephropathy. In vitro, triptolide ameliorated puromycin-induced cytoskeletal rearrangement and apoptosis via reactive oxygen species-mediated mitochondrial pathway. In addition, minnelide caused no reproductive toxicity to male and female mice. The results suggested that minnelide might be a promising drug for nephrotic syndrome.

ESTROGEN ALLEVIATES POSTHEMORRHAGIC SHOCK MESENTERIC LYMPH-MEDIATED LUNG INJURY THROUGH AUTOPHAGY INHIBITION.

ABSTRACT: Background: Hemorrhagic shock-induced acute lung injury (ALI) is commonly associated with the posthemorrhagic shock mesenteric lymph (PHSML) return. Whether excessive autophagy is involved in PHSML-mediated ALI remains unclear. The relationship between estrogen treatment and PHSML or autophagy needs to verify. The current study will clarify the role of estrogen in reducing PHSML-mediated ALI through inhibition of autophagy. Methods: First, a hemorrhagic shock model in conscious rats was used to observe the effects of 17ß-estradiol (E2) on intestinal blood flow, pulmonary function, intestinal and pulmonary morphology, and expression of autophagy marker proteins. Meanwhile, the effect of PHSML and autophagy agonist during E2 treatment was also investigated. Secondly, rat primary pulmonary microvascular endothelial cells were used to observe the effect of PHSML, PHSML plus E2, and E2-PHSML (PHSML obtained from rats treated by E2) on the cell viability. Results: Hemorrhagic shock induced intestinal and pulmonary tissue damage and increased wet/dry ratio, reduced intestinal blood flow, along with pulmonary dysfunction characterized by increased functional residual capacity and lung resistance and decreased inspiratory capacity and peak expiratory flow. Hemorrhagic shock also enhanced the autophagy levels in intestinal and pulmonary tissue, which was characterized by increased expressions of LC3 II/I and Beclin-1 and decreased expression of p62. E2 treatment significantly attenuated these adverse changes after hemorrhagic shock, which was reversed by PHSML or rapamycin administration. Importantly, PHSML incubation decreased the viability of pulmonary microvascular endothelial cells, while E2 coincubation or E2-treated lymph counteracted the adverse roles of PHSML. Conclusions: The role of estrogen reducing PHSML-mediated ALI is associated with the inhibition of autophagy.

Minnelide combined with Angptl3 knockout completely protects mice with adriamycin nephropathy via suppression of TGF-ß1-Smad2 and p53 pathways.

Minimal change disease (MCD) is the common type of nephrotic syndrome in children. There is an urgent need to explore new treatment methods as current treatments have many drawbacks and cause significant side effects. Our group found that Angiopoietin-like protein 3 (Angptl3) is closely related to renal disease and Angptl3 knockout significantly alleviated proteinuria in mice with adriamycin nephropathy (AN), however, some proteinuria was still present. Minnelide is a water-soluble prodrug of triptolide which has been used for the treatment of glomerular diseases. Therefore, this study aimed to investigate whether minnelide, combined with Angptl3 knockout, could completely protect mice with AN and its mechanism. AN was induced in B6;129S5 female mice by tail vein injection of 25 mg/kg of Adriamycin (ADR), and treatment with 200 ug/kg/d of minnelide. The results showed that minnelide combined with Angptl3 knockout completely reduced proteinuria and restored the foot processes in mice with AN. Moreover, in Angptl3 knockout mice with AN, minnelide restored the distribution of nephrin, podocin and cd2ap and reduced inflammatory factors (Tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-1ß (IL-1ß)). Through RNA sequencing and related experiments, we found minnelide could ameliorate fibrosis and apoptosis by inhibiting TGF-ß1-Smad2 and p53 pathways in Angptl3 knockout mice with AN, respectively. In Angptl3 knockout primary podocytes, triptolide alleviates ADR-induced decreases in nephrin, podocin and cd2ap, upregulation of Bax and downregulation of Bcl-2. Overall, our study shows that minnelide combined with Angptl3 knockout completely protects mice with AN by inhibiting the TGF-ß1-smad2 and p53 pathways.

Self-Assembled CuCo2S4 Nanoparticles for Efficient Chemo-Photothermal Therapy of Arterial Inflammation.

Cardiovascular disease caused by atherosclerosis (AS) seriously affects human health. Photothermal therapy (PTT) brings hope to the diagnosis and treatment of AS, with the development of nanotechnology. To improve treatment efficiency, self-assembled CuCo2S4 nanocrystals (NCs) were developed as a drug-delivery nanocarrier, triggered by near-infrared (NIR) light for efficient chemophotothermal therapy of arterial inflammation. The as-prepared self-assembled CuCo2S4 NCs exhibited excellent biocompatibility and a very high chloroquine (CL)-loading content. In addition, the self-assembled CuCo2S4 NCs/CL nanocomposites showed good photothermal performance, due to strong absorption in the NIR region, and the release of CL from the NCs/CL nanocomposites was driven by NIR light. When illuminated by NIR light, both PTT from the NCs and chemotherapy from the CL were simultaneously triggered, resulting in killing macrophages with a synergistic effect. Moreover, chemo-photothermal therapy with CuCo2S4 NCs/CL nanocomposites showed an effective therapeutic effect for arterial inflammation, in vivo. Our work demonstrated that chemo-photothermal therapy could be a promising strategy for the treatment of arterial inflammation against atherosclerosis.

Light-activated gold nanorods for effective therapy of venous malformation.

Gold nanorods have been studied extensively in the field of tumor therapy but have not been explored in the treatment of venous malformation (VM), which is a common vascular disease in clinic practice lacking an effective therapeutic approach. Herein we reported a nanoplatform of CD31 antibody-conjugated gold nanorods for the photothermal therapy of venous malformation. We immobilized CD31 antibodies on gold nanorods using standard 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysulfosuccinimide sodium (NHS) amine coupling strategies. Besides, a VM xenograft model suitable for testing therapeutic efficacy was established by isolating and culturing VM patient endothelial cells. In vitro experiments indicated that anti-CD31 gold nanorods (GNRs) combined with photothermal therapy (PTT) contributed to the suppression of proliferation and activation of the apoptosis pathway. For in vivo experiments, anti-CD31 GNRs were locally injected into VM xenograft models followed by near infrared (NIR) 808 â€‹nm laser irradiation. Notably, VM on the mice was destroyed and absorbed. The anti-CD31 GNRs nanoplatform may serve as a new strategy for the treatment of VM which is of good biosafety and high value of applications.

Butyrate promotes oral squamous cell carcinoma cells migration, invasion and epithelial-mesenchymal transition.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the most common type of primary malignant tumor in the oral cavity, is a lethal disease with high recurrence and mortality rates. Butyrate, a metabolite produced by periodontal pathogens, has been linked to oral diseases. The purpose of this study was to evaluate the effect of sodium butyrate (NaB) on the proliferation, migration, and invasion of OSCC cells in vitro and to explore the potential mechanism. METHODS: Two OSCC cell lines (HSC-4 and SCC-9) were treated with NaB at different concentrations. The cell proliferation was assayed by CCK-8, ethylene deoxyuridine (EdU), and flow cytometry. Wound healing and transwell assay were performed to detect cell migration and invasion. Changes in epithelial-mesenchymal transition (EMT) markers, including E-cadherin, Vimentin, and SNAI1, were evaluated by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescent staining. The expression levels of matrix metalloproteinases (MMPs) were analyzed by qRT-PCR and gelatin zymography. RESULTS: Our results showed that NaB inhibited the proliferation of OSCC cells and induced cell cycle arrest at G1 phase, but NaB significantly enhanced cell migration and invasion compared with the control group. Further mechanistic investigation demonstrated that NaB induced EMT by increasing the expression of Vimentin and SNAI1, decreasing the expression of membrane-bound E-cadherin, and correspondingly promoting E-cadherin translocation from the membrane to the cytoplasm. In addition, the overexpression of MMP1/2/9/13 was closely related to NaB treatment. CONCLUSIONS: Our study conclude that butyrate may promote the migration and invasion of OSCC cells by inducing EMT. These findings indicate that butyrate may contribute to OSCC metastasis.

Podocyte protection by Angptl3 knockout via inhibiting ROS/GRP78 pathway in LPS-induced acute kidney injury.

Acute kidney injury (AKI) caused by sepsis has a high incidence and poor prognosis. Thus, novel strategies that minimize AKI are urgently needed. In our previous research, we found that angiopoietin-like protein 3 (Angptl3) knockout exerts protective effects on kidney injury in adriamycin nephropathy. However, the role of Angptl3 in the pathogenesis of AKI is largely unclear. This study aimed to explore the renal protective effects and molecular mechanisms of Angptl3 knockout in lipopolysaccharide (LPS)-induced AKI in mice. B6;129S5 mice were injected intraperitoneally with 10 mg/kg of LPS to induce AKI. Then, the changes in renal function, podocyte apoptosis, inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; and interleukin-1ß, IL-1ß), reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress were measured. The mechanism of Angptl3 in the apoptosis of podocytes was also investigated. Results showed that Angptl3 knockout significantly alleviated the renal dysfunction and apoptosis of podocytes induced by LPS. Angptl3 knockout was associated with the (1) downregulation of Bax and upregulation of Bcl-2; (2) amelioration of the abnormal expression of nephrin, podocin, and CD2AP; (3) reduced ER stress; (4) reduced secretions of TNF-α, IL-6, and IL-1ß; and (5) regulation of Bax expression via the ROS-related ER stress pathway. Our findings revealed that Angptl3 knockout alleviated the apoptosis of podocytes by regulating the ROS/GRP78 signaling pathway.

sRNA23392 packaged by Porphyromonas gingivalis outer membrane vesicles promotes oral squamous cell carcinomas migration and invasion by targeting desmocollin-2.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignant tumor. Periodontitis, a common chronic inflammatory disease, has been proven to increase the risk of oral cancers. Porphyromonas gingivalis (P. gingivalis), the major pathogen in periodontal disease, was recently shown to promote the development of OSCC. However, the underlying mechanisms have not been defined. Emerging evidence suggests that P. gingivalis outer membrane vesicles (OMVs) contain different packaged small RNAs (sRNAs) with the potential to target host mRNA function and/or stability. In this study, we found that P. gingivalis OMVs promote the invasion and migration of OSCC cells in vitro. Further research showed that sRNA23392 was abundant in P. gingivalis OMVs and it promoted the invasion and migration of OSCC cells by targeting desmocollin-2 (DSC2). DSC2, a desmosomal cadherin family member, has been found to be involved in tumor progression. sRNA23392 inhibitors attenuated P. gingivalis OMV-induced migration and invasion of OSCC cells. Collectively, these findings are consistent with the hypothesis that sRNA23392 in P. gingivalis OMVs is a novel mechanism of the host-pathogen interaction, whereby P. gingivalis promotes the invasion and migration of OSCC.

Can S100B Predict and Evaluate Post-Traumatic Hydrocephalus.

OBJECTIVE: Post-traumatic hydrocephalus (PTH) is a common complication of craniocerebral injury. If not diagnosed in time, PTH can lead to clinical deterioration and a poor prognosis. The early diagnosis of PTH can lead to success with early treatment. However, PTH can be easily ignored during rehabilitation. The main purpose of the present study was to investigate whether plasma S100B protein levels can be used as a biochemical predictive index of PTH. We also explored the correlation among S100B protein levels, intracranial pressure, and PTH severity. METHODS: The data from 235 patients with traumatic brain injury treated from June 2014 to June 2019 in our hospital were retrospectively analyzed. Statistical analysis was performed on 3 serum S100B samples from each patient. The first sample was taken 1-3 days after the injury and surgery. The second sample was harvested during the stable period after treatment, and the third sample was taken when PTH had been confirmed by computed tomography. We analyzed the change in S100B protein levels, and intracranial pressure was measured by lumbar puncture. RESULTS: A total of 235 patients (Glasgow coma scale score <12) with traumatic brain injury were investigated. Of these 235 patients, 46 (19%) had developed PTH. The first and second S100B samples showed no significant differences between the patients with and without PTH. In the third sample, the S100B level of the patients with PTH was significantly greater than that of the patients without PTH, with a statistically significant difference. Statistical analysis found no correlation between the S100B level and the severity of PTH. CONCLUSIONS: Measurements of serum S100B can be used to predict for PTH. We found a positive correlation between S100B levels and intracranial pressure but no correlation with the severity of PTH. Thus, serum S100B could have important clinical significance for the early detection and evaluation of PTH.

Analysis of differentially expressed genes in oral epithelial cells infected with Fusobacterium nucleatum for revealing genes associated with oral cancer.

Accumulating evidence links Fusobacterium nucleatum with tumorigenesis. Our previous study demonstrated that F. nucleatum infection can induce epithelial-mesenchymal transition (EMT) in oral epithelial cells and elaborated a probable signal pathway involved in the induction of EMT. However, the comprehensive profiling and pathways of other candidate genes involved in F. nucleatum promoting malignant transformation remain largely elusive. Here, we analysed the transcriptome profile of HIOECs exposed to F. nucleatum infection. Totally, 3307 mRNAs (ǀLog2FCǀ >1.5) and 522 lncRNAs (ǀLog2FCǀ >1) were identified to be differentially expressed in F. nucleatum-infected HIOECs compared with non-infected HIOECs. GO and KEGG pathway analyses were performed to investigate the potential functions of the dysregulated genes. Tumour-associated genes were integrated, and top 10 hub genes (FYN, RAF1, ATM, FOS, CREB, NCOA3, VEGFA, JAK2, CREM and ATF3) were identified by protein-protein interaction (PPI) network, and Oncomine was used to validate hub genes' expression. LncRNA-hub genes co-expression network comprising 67 dysregulated lncRNAs were generated. Together, our study revealed the alteration of lncRNA and potential hub genes in oral epithelial cells in response to F. nucleatum infection, which may provide new insights into the shift of normal to malignant transformation initiated by oral bacterial infection.

Clinical Evaluation a New Treatment for Infection After Ventriculoperitoneal Shunt.

ABSTRACT: To explore a new surgical treatment for infection and obstruction of ventriculoperitoneal shunt in hydrocephalus. Two cases of post-operative infection of ventriculoperitoneal shunt were analyzed retrospectively. One case was cryptococcal infection, the other case was Acinetobacter lwoffii. The number of cerebrospinal fluid cells was high, the infection of ventriculoperitoneal shunt was generally complicated with abdominal obstruction, and the hydrocephalus was aggravated again, The authors try to pull out the drainage tube at the end of abdominal cavity for external drainage, combined with intravenous antibiotics, completely control of infection, and then use the original shunt device for intraventricular jugular shunt. The authors explore that this method is simple, safe and effective, and it is an effective and feasible method for the treatment of infection after ventriculoperitoneal shunt.

Interaction of Estradiol and Endoplasmic Reticulum Stress in the Development of Esophageal Carcinoma.

Gender differences in esophageal cancer patients indicate that estradiol may have antitumor effects on esophageal cancer. The initiation of endoplasmic reticulum stress (ERS) can induce apoptosis in esophageal cancer cells. However, it is still unknown whether estradiol inhibits the development of esophageal cancer by activating ERS pathway. In this study, the gender difference in the development of esophageal cancer was observed by analyzing clinical data and the experimental tumor xenografts in mice. Meanwhile, we investigated the mechanism of ERS in estradiol-mediated inhibition of esophageal cancer using esophageal squamous cell carcinoma cell line EC109. The proportion of male patients with esophageal cancer was significantly higher than female patients. Meanwhile, male patients were prone to have adventitial invasion. The weight of transplanted tumors in female mice was significantly smaller than that in male mice. In vitro experiments showed estradiol inhibits the viability and migration of EC109 cells by increasing the expression of ERS-related proteins, whereas ERS inhibitor 4-PBA abolished the effects of estradiol. In conclusion, our data demonstrate that sex difference exists in the occurrence of esophageal cancer. Estradiol can inhibit the viability and migration of esophageal cancer cells through the activation of ERS, providing a novel insight for esophageal cancer development, treatment, and prevention.

Allogeneic adipose-derived stem cells promote ischemic muscle repair by inducing M2 macrophage polarization via the HIF-1α/IL-10 pathway.

Adipose-derived mesenchymal stem cells (ASCs) are multipotent stromal cells that possess considerable therapeutic potential for tissue remodeling. However, their protective mechanism in critical limb ischemia has not been fully defined. After the occlusion of blood vessels, hypoxia becomes a prominent feature of the ischemic limb. This study investigated the immunomodulatory effect of ASCs on ischemic muscle repair and explored the specific mechanism. We found that the ability of RAW264.7 cells to migrate was impaired in hypoxia, whereas coculturing with ASCs could enhance the migration capacity. In addition, under hypoxic conditions, the paracrine effect of ASCs was enhanced and ASCs could induce RAW264.7 macrophages toward the anti-inflammatory M2 phenotype. We further demonstrated that ASCs-derived interleukin 10 (IL-10), mediated by hypoxia inducible factor-1α (HIF-1α), played a crucial role in the induction of M2 macrophages by activating the signal transducer and activator of transcription 3 (STAT3)/Arginase (Arg-1) pathway. Our in vivo experiments revealed that transplanted ASCs exhibited an immunomodulatory effect by recruiting macrophages to ischemic muscle and increasing the density of M2 macrophages. The transplantation of ASCs into ischemic limbs induced increased blood flow reperfusion and limb salvage rate, whereas the depletion of tissue macrophages or transplanting HIF-1α-silenced ASCs inhibited the therapeutic effect. These findings elucidated the critical role of macrophages in ASCs-mediated ischemic muscle repair and proved that allogeneic ASCs could exert the protective effect by enhancing the recruitment of macrophages and inducing macrophages toward M2 phenotype through HIF-1α/IL-10 pathway.

Composition and function of oral microbiota between gingival squamous cell carcinoma and periodontitis.

OBJECTIVES: Previous studies have proved that periodontitis is an independent risk factor of oral squamous cell carcinoma (OSCC) epidemiologically. Along with the important role of microbiota in the cancer process and the specific anatomical position, our study explored the microbial composition and functions in periodontitis and gingival squamous cell carcinoma (GSCC). MATERIALS AND METHODS: GSCC patients (n = 10), matched periodontitis patients (n = 15), and healthy individuals (n = 15) were recruited. Saliva, subgingival plaque, tongue dorsum, buccal mucosa, cancerous tissue, and paracancerous tissue samples were collected. 16S rDNA amplicon sequencing and functional prediction were applied for the taxonomic analysis. RESULTS: Periodontal pathogens occupied 46% in GSCC. Besides, the mutual operational taxonomy unites (OTU) generated from the subgingival plaque occupied 38.36% and 44.13% from saliva. Fusobacterium, Peptostreptococcus, and Prevotella were more abundant in cancerous tissues, while Streptococcus, Neisseria, and Haemophilus were more enriched in saliva or soft mucosa. PCoA exhibited similar cluster between tongue dorsum and saliva in GSCC. GSCC showed lower richness than periodontitis. In saliva and subgingival plaque, Atopobium was more prevalent in GSCC than periodontitis and controls in descending order. Lipopolysaccharide (LPS) biosynthesis increased in subgingival plaque of GSCC compared with the other two groups. CONCLUSION: Periodontal pathogens were abundant in GSCC. Cancerous tissues harbor enriched periodontal pathogens while saliva or soft mucosa harbored more periodontal health related bacteria. A high level of Atopobium in saliva and LPS biosynthesis have the potential for increasing the risk of suffering from GSCC in individuals with periodontitis, which needs more evidence to clarify it.

A meta-analysis of combined proximal stent grafting with or without adjunctive distal bare stent for the management of aortic dissection.

BACKGROUND: The efficacy and safety of placement of a proximal covered stent graft combined with a distal bare stent are controversial because of the lack of evidence. This systematic review and meta-analysis compared the outcomes of combined proximal covered stent grafting with distal bare stenting (BS group) and proximal covered stent grafting without distal bare stenting (non-BS group). METHODS: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and key references were searched up to January 26, 2019. Predefined outcomes of interest were mortality, morbidity, and postoperative assessment of aortic remodeling. We pooled risk ratios (RRs) of the outcomes of interest using fixed effects model or random effects model. RESULTS: Overall, eight observational studies involving 914 patients were included. There were no significant differences in overall aorta-related mortality (RR, 0.54; confidence interval [CI], 0.24-1.24; P = .15), complete thoracic false lumen (FL) thrombosis rate (RR, 1.23; CI, 0.83-1.81; P = .30), or complete abdominal FL thrombosis rate (RR, 1.96; CI, 0.68-5.69; P = .21) between the BS group and the non-BS group. The BS group had a lower rate of partial thoracic FL thrombosis (RR, 0.40; CI, 0.25-0.65; P = .0002), a lower stent graft-induced new entry rate (RR, 0.08; CI, 0.02-0.41; P = .003), and a lower reintervention rate (RR, 0.42; CI, 0.26-0.69; P = .0005). CONCLUSIONS: Combined proximal covered stent grafting with distal adjunctive bare stenting had the potential to reduce the partial thoracic FL thrombosis rate and the rates of stent graft-induced new entry and reintervention but was not associated with lower aorta-related mortality or the complete FL thrombosis rate. Further research with a stricter methodology is needed.

Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway.

Fusobacterium nucleatum, an anaerobic oral opportunistic pathogen associated with periodontitis, has been considered to be associated with the development of oral squamous cell carcinoma (OSCC). However, the initial host molecular alterations induced by F. nucleatum infection which may promote predisposition to malignant transformation through epithelial-mesenchymal transition (EMT) have not yet been clarified. In the present study, we monitored the ability of F. nucleatum to induce EMT-associated features, and our results showed that F. nucleatum infection promoted cell migration in either noncancerous human immortalized oral epithelial cells (HIOECs) or the two OSCC cell lines SCC-9 and HSC-4, but did not accelerate cell proliferation or cell cycle progression. Mesenchymal markers, including N-cadherin, Vimentin, and SNAI1, were upregulated, while E-cadherin was decreased and was observed to translocate to the cytoplasm. Furthermore, FadA adhesin and heat-inactivated F. nucleatum were found to cause a similar effect as the viable bacterial cells. The upregulated lncRNA MIR4435-2HG identified by the high-throughput sequencing was demonstrated to negatively regulate the expression of miR-296-5p, which was downregulated in F. nucleatum-infected HIOECs and SCC-9 cells. The binding of MIR4435-2HG and miR-296-5p was validated via a dual-luciferase reporter assay. Additionally, knockdown of MIR4435-2HG with siRNA leads to a decrease in SNAI1 expression, while miR-296-5p could further negatively and indirectly regulate SNAI1 expression via Akt2. Therefore, our study demonstrated that F. nucleatum infection could trigger EMT via lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway, and EMT process may be a probable link between F. nucleatum infection and initiation of oral epithelial carcinomas.

Copper chalcogenide materials as photothermal agents for cancer treatment.

Copper-based chalcogenide nanomaterials have made tremendous progress for cancer theranostics due to their simple preparation, low cost, stable performance, and easy functionalization. But a systematic review and analysis about them does not exist. Therefore, we offer an account, mainly focusing on the design and functionalization of the copper-based chalcogenide nanomaterials for cancer theranostics, aiming to briefly demonstrate the design and concepts, summarize some of the past studies and analyze the development trends in the copper-based chalcogenide nanomaterials for clinical application.

Distinct gene expression characteristics in epithelial cell-Porphyromonas gingivalis interactions by integrating transcriptome analyses.

Porphyromonas gingivalis is a pivotal periodontal pathogen, and the epithelial cells serve as the first physical barrier to defend the host from bacterial attack. Within this host-bacteria interaction, P. gingivalis can modify the host immune reaction and adjust the gene expression, which is associated with periodontitis pathogenesis and developing strategies. Herein, a meta-analysis was made to get the differential gene expression profiles in epithelial cells with or without P. gingivalis infection. The network-based meta-analysis program for gene expression profiling was used. Both the gene ontology analysis and the pathway enrichment analysis of the differentially expressed genes were conducted. Our results determined that 290 genes were consistently up-regulated in P. gingivalis infected epithelial cells. 229 gene ontology biological process terms of up-regulated genes were discovered, including "negative regulation of apoptotic process" and "positive regulation of cell proliferation/migration/angiogenesis". In addition to the well-known inflammatory signaling pathways, the pathway associated with a transcriptional misregulation in cancer has also been increased. Our findings indicated that P. gingivalis benefited from the survival of epithelial cells, and got its success as a colonizer in oral epithelium. The results also suggested that infection of P. gingivalis might contribute to oral cancer through chronic inflammation. Negative regulation of the apoptotic process and transcriptional misregulation in cancer pathway are important contributors to the cellular physiology changes during infection development, which have particular relevance to the pathogenesis and progressions of periodontitis, even to the occurrence of oral cancer.