Targeting Gas6/TAM in cancer cells and tumor microenvironment.

Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

Antiangiogenic and antihepatocellular carcinoma activities of the Juniperus chinensis extract.

BACKGROUND: To identify a novel therapeutic agent for hepatocellular carcinoma (HCC), for which no promising therapeutic agent exists, we screened a panel of plants and found that Juniperus chinensis exhibited potential antiangiogenic and anti-HCC activities. We further investigated the antiangiogenic and anti-HCC effects of the active ingredient of J. chinensis extract, CBT-143-S-F6F7, both in vitro and in vivo. METHODS: A tube formation assay conducted using human umbilical vein endothelial cells (HUVECs) was first performed to identify the active ingredient of CBT-143-S-F6F7. A series of angiogenesis studies, including HUVEC migration, Matrigel plug, and chorioallantoic membrane (CAM) assays, were then performed to confirm the effects of CBT-143-S-F6F7 on angiogenesis. The effects of CBT-143-S-F6F7 on tumor growth were investigated using a subcutaneous and orthotopic mouse model of HCC. In vitro studies were performed to investigate the effects of CBT-143-S-F6F7 on the cell cycle and apoptosis in HCC cells. Moreover, protein arrays for angiogenesis and apoptosis were used to discover biomarkers that may be influenced by CBT-143-S-F6F7. Finally, nuclear magnetic resonance analysis was conducted to identify the compounds of CBT-143-S-F6F7. RESULTS: CBT-143-S-F6F7 showed significantly antiangiogenic activity in various assays, including HUVEC tube formation and migration, CAM, and Matrigel plug assays. In in vivo studies, gavage with CBT-143-S-F6F7 significantly repressed subcutaneous Huh7 tumor growth in severe combined immunodeficient (SCID) mice, and prolonged the survival of orthotopic Huh7 tumor-bearing SCID mice (a 40 % increase in median survival duration compared with the vehicle-treated mice). Immunohistochemical staining of subcutaneous Huh7 tumors in CBT-143-S-F6F7-treated mice showed a significantly decrease in the cell cycle regulatory protein cyclin D1, cellular proliferation marker Ki-67, and endothelial marker CD31. CBT-143-S-F6F7 caused arrest of the G2/M phase and induced Huh7 cell apoptosis, possibly contributing to the inhibition of HCC tumors. Protein array analysis revealed that several angiogenic and antiapoptotic factors were suppressed in CBT-143-S-F6F7-treated Huh7 cells. Finally, five compounds from CBT-143-S-F6F7 were identified. CONCLUSIONS: According to these results, we report for the first time the antiangiogenic and anti-HCC activities of CBT-143-S-F6F7, the active fractional extract of J. chinensis. We believe that CBT-143-S-F6F7 warrants further evaluation as a new anti-HCC drug.

Restricted cubic spline model analysis of the association between anal fistula and anorectal abscess incidence and body mass index.

Objective: The epidemiological profile of anal fistula and anorectal abscess has not been well studied. Based on the results of a retrospective cross-sectional survey, we aimed to investigate the potential influential factors associated with anal fistula and anorectal abscess. Methods: We conducted a retrospective analysis of outpatients who visited the proctology department at China-Japan Friendship Hospital between January 2017 and May 2022. A comprehensive questionnaire was designed to collect potential influential factors, and according to formal anorectal examination and the corresponding diagnostic criteria, all the participants were divided into patients with anal fistula or perianal abscess and healthy control group. Multiple logistic regression was used to identify factors in significant association with anal fistula and perianal abscess. Additionally, we combined restricted cubic spline regression to examine the dose-response relationship between factors and the risk of developing anal fistula or anorectal abscess. Results: The present study included 1,223 participants, including 1,018 males and 206 females, with 275 anal fistulas, 184 anorectal abscesses, and 765 healthy controls. We found no statistically significant differences between patients and controls in basic information and preoperative assessment of life factors, except for body mass index. It was indicated that people with overweight or obesity were more prone to anal fistula (OR overweight = 1.35, 95% CI: 1.00-1.82, P = 0.047; OR obesity = 3.44, 95% CI: 2.26-5.26, P < 0.001) or anorectal abscess (OR overweight = 1.41, 95% CI: 1.00-1.99, P = 0.05; OR obesity: 2.24, 95% CI: 1.37-3.67, P = 0.001) than normal-weight individuals. The dose-response research indicated the J-shaped trend between the ascending BMI levels and the higher risk of suffering from anal fistula and anorectal abscess. Conclusions: Our findings indicate that overweight and obesity are risk factors for anal fistula and anorectal abscess, which plays a role in the prevention of anorectal diseases. This provides some theoretical basis for clinicians to provide health education to their patients.

Two-finger digital rectal examination for the diagnosis of anal fistula: protocol for a randomized controlled trial.

Background: Anal fistula is an anorectal infectious disease caused by a perianal abscess or perianal disease. Accurate anorectal examinations are of great significance. The two-finger digital rectal examination (TF-DRE) has been used in clinical practice, with a lack of comprehensive research on the value of the TF-DRE in the diagnosis of anal fistula. This study will compare the difference in the diagnostic value of the TF-DRE, traditional digital rectal examination (DRE), and anorectal ultrasonography in the diagnosis of anal fistula. Methods: For patients who meet the inclusion criteria, a TF-DRE will be performed to explore the number and location of the external and internal orifices, the number of fistulas, and the relationship between the fistula and the perianal sphincter. A DRE and anorectal ultrasonography will also be performed, and the same data will be recorded. To make a comparison, the final diagnosis results of the clinicians during the operation will be taken as the gold standard, the accuracy of the TF-DRE in diagnosing anal fistula will be calculated, and the significance of the TF-DRE in the preoperative diagnosis of anal fistula will be studied and analyzed. All the statistical results will be analyzed using SPSS22.0 (IBM, USA), and a P value <0.05 will be considered statistically significant. Discussion: The research protocol details the advantages of the TF-DRE compared to the DRE and anorectal ultrasonography in the diagnosis of anal fistula. This study will provide clinical evidence of the diagnostic value of the TF-DRE in the diagnosis of anal fistula. Currently, there is a lack of high-quality research using scientific methods on this innovative anorectal examination method. This study will provide rigorously designed clinical evidence on the TF-DRE. Registration: Chinese Clinical Trials Registry ChiCTR2100045450.

Maintenance of multipotency of bone marrow mesenchymal stem cells on poly(ε-caprolactone) nanoneedle arrays through the enhancement of cell-cell interaction.

Mesenchymal stem cells (MSCs), with high self-renewal ability and multipotency, are commonly used as the seed cells for tissue engineering. However, the reduction and loss of multipotential ability after necessary expansion in vitro set up a heavy obstacle to the clinical application of MSCs. Here in this study, we exploit the autologous crystallization ability of biocompatible poly (ε-caprolactone) (PCL) to obtain uniformly distributed nanoneedle arrays. By controlling the molecular weight of PCL, nanoneedle with a width of 2 µm and height of 50 nm, 80 nm, and 100 nm can be successfully fabricated. After surface chemical modification with polydopamine (PDA), the water contact angle of the fabricated PCL nanoneedle arrays are reduced from 84° to almost 60° with no significant change of the nanostructure. All the fabricated substrates are cultured with bone marrow MSCs (BMMSCs), and the adhesion, spreading, proliferation ability and multipotency of cells on different substrates are investigated. Compared with the BMMSCs cultured on pure PCL nanoneedle arrays, the decoration of PDA can improve the adhesion and spreading of cells and further change them from aggregated distribution to laminar distribution. Nevertheless, the laminar distribution of cultured cells leads to a weak cell-cell interaction, and hence the multipotency of BMMSCs cultured on the PCL-PDA substrates is decimated. On the contrary, the pure PCL nanoneedle arrays can be used to maintain the multipotency of BMMSCs via clustered growth, and the PCL1 nanoneedle array with a height of 50 nm is more promising than the other 2 with regard to the highest proliferation rate and best multipotential differentiation ability of cultured cells. Interestingly, there is a positive correlation between the strength of cell-cell interaction and the multipotency of stem cells in vitro. In conclusion, we have successfully maintained the multipotency of BMMSCs by using the PCL nanoneedle arrays, especially the PCL1 nanoneedle array with a height of 50 nm, as the substrates for in vitro extension, and further revealed the importance of cell-cell interaction on the multipotency of MSCs. The study provides a theoretical basis for the behavioral regulation of MSCs, and is instructive to the design of tissue engineering scaffolds.

Clinical study on the effectiveness and safety of loose combined cutting seton in the treatment of high perianal abscess: a randomized controlled trial protocol.

Background: High perianal abscess is an emergency in the anorectal department. It can result in long-term pain and a huge psychological burden to patients, and seriously affects the quality of life of patients. At present, the effect of antibiotics alone for high perianal abscess is not satisfactory. Loose combined cutting seton (LCCS) can effectively treat high anal fistulas and high perianal abscesses in our clinical practice, but there is no sufficient evidence for its effectiveness in the treatment of high perianal abscesses. The purpose of this study is to observe the effectiveness and safety of LCCS in the treatment of high perianal abscess. Methods: This study is a single-center, prospective, single-blind, randomized, controlled, non-inferiority clinical study. This study will include patients who are diagnosed with high perianal abscesses and hospitalized for surgery in the Department of Proctology in China-Japan Friendship Hospital (enrollment time: from January 2022 through December 2024). Patients in the experimental group will be treated with LCCS, while patients in the control group will be treated with incision and drainage. Follow-ups will be performed at 1, 3, 7, 14, 21, 28, 90, and 180 days after the operation. The main outcome measures are as follows: (I) cure rate; (II) half-year recurrence rate; (III) postoperative pain visual analog scale (VAS) score; (IV) wound healing time; (V) postoperative anal function evaluation by the Wexner scale; (VI) pressure measurement of the anal canal and rectum before and at half a year after surgery; and (VII) the incidence of adverse events. Discussion: This study will assess the effectiveness and safety of LCCS in the treatment of high perianal abscess through a strictly designed randomized controlled study, and provides evidence for treatment in clinical practice, thereby improving the treatment effect and improving patients' quality of life. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100049198.

Energy-Resolved Ultrafast Spectroscopic Investigation on the Spin-Coupled Electronic States in Multiferroic Hexagonal HoMnO3.

A complete temperature-dependent scheme of the Mn3+ on-site d-d transitions in multiferroic hexagonal HoMnO3 (h-HoMnO3) thin films was unveiled by energy-resolved ultrafast spectroscopy. The results unambiguously revealed that the ultrafast responses of the e1g and e2g states differed significantly in the hexagonal HoMnO3. We demonstrated that the short-range antiferromagnetic and ferroelectric orderings are more relevant to the e2g state, whereas the long-range antiferromagnetic ordering is intimately coupled to both the e2g and e1g states. Moreover, the primary thermalization times of the e2g and e1g states were 0.34 ± 0.08 ps and 0.38 ± 0.08 ps, respectively.

A systematic review and meta-analysis of incision and seton drainage in the treatment of high perianal abscess.

BACKGROUND: Surgery is the clinically preferred treatment for high perianal abscesses. Incision and seton drainage improve the cure rate and reduce recurrence. We aimed to systematically evaluate the clinical effect and safety of incision and seton drainage in the treatment of high perianal abscess. METHODS: China Knowledge Network (CNKI), WanFang database, VIP database, PubMed, and Cochrane Library were searched and all relevant Chinese and English language documents until July 2021were retrieved. All records that described randomized clinical trials (RCTs) of incision and seton drainage for the treatment of high perianal abscess were eligible. Documents that met the inclusion criteria were evaluated for bias using the Cochrane Collaboration Risk Evaluation Standard, and Revman5.4 software was used to analyze the data. RESULTS: Fourteen RCTs were included. The results of nine studies showed that the clinical cure rate of the incision-seton group was higher than that of the incision-drainage group (P<0.05). Seven studies showed that the wound healing time of the incision-seton group was shorter than that of the incision-drainage group (P<0.05). Four studies showed that the visual analogue scale (VAS) score of the incision-seton group was lower than that of the incision-drainage group (P<0.05). Five studies showed that the Wexner score of the incision-seton group was lower than that of the incision-drainage group (P<0.05). Six studies showed that the formation rate of anal fistula in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Six studies demonstrated that the recurrence rate of abscess in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Seven studies showed that the incidence of adverse events in the incision-seton group was lower than that in the incision-drainage group (P<0.05). Five studies demonstrated that the length of stay in the incision-seton group was shorter than that of the incision-drainage group (P<0.05). DISCUSSION: The choice of surgical methods in clinical research has always been controversial. The incision-seton method can effectively and safely treat high perianal abscess. However, the results of this meta-analysis still leave some gaps in the evidence. More large-sample, high-quality, and multi-center RCTs are needed.

Research on high anal fistula: a bibliometric analysis.

BACKGROUND: High anal fistula (HAF) treatment is more complicated than low anal fistula treatment. Improper treatment can easily affect anal function. The main treatment of HAF is surgery; however, external medicine and systemic medicine may also be used as adjuvant treatments. This study used bibliometric methods to analyze the relevant literature and provide a rough outline of the current status of HAF research. METHODS: A subject word-search strategy was used to retrieve HAF-related documents from the Science Citation Index Expanded (SCI-E) database. CiteSpace software was used to analyze the exported raw data files, and draw a visual map, and BUSRT was used to detect and analyze the usage of keywords. RESULTS: A total of 1,020 documents were retrieved using "high anal fistula" as the search term, and the number of documents generally shows an increasing trend over time. These papers were mainly published in developed countries, such as Europe and the United States (US). The US is the country that has carried out the most relevant cooperative research; however, there is a lack of cooperation among a large number of authors. The keyword analysis showed that the current research focus is the treatment of HAF, while research on the prevention of HAF is largely lacking. CONCLUSIONS: More international multi-center clinical research studies on HAF should be conducted, and research on HAF prevention should also be strengthened.

Rare case of granular cell tumor of perianal region: a case report and literature review.

Granular cell tumors (GCTs) are rare submucosal neoplasms, with tumors in the oral mucosa accounting for about a third of all cases. In contrast, GCT is a rare anal neoplasm, with fewer than 30 cases of perianal GCT reported in the literature. We report the case of a 36-year-old woman with a perianal lump with no obvious local lesion as the main clinical complaint. The tumor was completely resected and histologically confirmed as a GCT. The patient remained under continuous follow-up. GCT is difficult for surgeons and pathologists to diagnose, and biopsy and immunohistochemical analysis are prerequisites for an accurate diagnosis. An integrated understanding of GCT in terms of its differential diagnosis will contribute to better identification and more appropriate treatment of this disease.

Long-term antibacterial activity of a composite coating on titanium for dental implant application.

Dental implants are the most innovative and superior treatment modality for tooth replacement. However, titanium implants still suffer from insufficient antibacterial capability and peri-implant diseases remain one of the most common and intractable complications. To prevent peri-implant diseases, a composite coating containing a new antibacterial agent, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF) was fabricated on titanium. This study was designed to investigate the antibacterial activity of the composite coating against two common peri-implant pathogens (Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans). The morphology of the composite coating showed that BBF-loaded poly(L-lactic acid) nanospheres were well-distributed in the pores of the microarc oxidation coating, and cross-linked with each other and the wall pores by gelatin. A release study indicated that the antibacterial coating could sustain the release of BBF for 60 d, with a slight initial burst release occurring during the first 4 h. The antibacterial rate of the composite coating for adhering bacteria was the highest (over 97%) after 1 d and over 90% throughout a 30-day incubation period. The total fluorescence intensity of the composite coating was the lowest, and the vast majority of the fluorescence was red (dead bacteria). Moreover, real-time polymerase chain reaction analysis confirmed that the relative gene expression of the adherent bacteria on the composite coating was down-regulated. It was therefore concluded that the composite coating fabricated on titanium, which showed excellent and relatively long-term antibacterial activity against Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, is a potential and promising strategy to be applied on dental implants for the prevention of peri-implant diseases.

Loose combined cutting seton for patients with suprasphincteric anal fistula: a randomized clinical trial protocol.

BACKGROUND: Suprasphincteric anal fistula is a type of high anal fistula. The traditional method of cutting seton (CS) has a high recurrence rate and can cause severe damage to the anal sphincter and anal incontinence. The combination of loose and cutting seton is a novel method developed on the basis of the traditional cutting seton technique, and has already been adopted by some clinicians in China. This study will examine the effectiveness and safety of the loose combined cutting seton (LCCS) technique for the treatment of suprasphincteric anal fistulas. METHODS: This is a single-blinded randomized controlled trial conducted in the Anorectal Department of the China-Japan Friendship Hospital. A total of 76 patients diagnosed with suprasphincteric anal fistula will be randomly divided into two groups. One group will be treated with the LCCS method (the LCCS group; n=38) and the other group will be treated with the traditional CS method (the CS group; n=38). There will be 3 intervention periods, including the screening period, the surgical treatment period, and the postoperative follow-up period. Postoperative follow-up will be carried out on days 3, 5, 7, 14, 21, 28, 90, 180, and 365 after the operation. The main outcome measures are the complete cure rate of postoperative wounds and fistulas, the long-term recurrence rate, and evaluation of postoperative anal function (Wexner anal function assessment and anal function questionnaire). The secondary outcomes are the visual analogue scale (VAS) score for postoperative pain, pressure measurements of the anal canal and rectum before and after treatment, and the incidence of adverse events. All statistical results will be analyzed using the SPSS software 21.0 version. P values <0.05 will be considered statistically significant. DISCUSSION: This research introduces a novel method for the treatment of suprasphincteric anal fistulas. The LCCS method will be compared with the traditional CS method in terms of safety and efficacy. If the LCCS technique is a safe and effective treatment for suprasphincteric anal fistula, its clinical application should be promoted. TRIAL REGISTRATION: ClinicalTrials, Registration number: ChiCTR2100045450; pre-results. PROTOCOL VERSION: 2020-09-10 1.0 version.

Simplified dressing change after loose combined cutting seton surgery for high anal fistula: a prospective, single center randomized controlled study.

BACKGROUND: High anal fistula (HAF) is a refractory infectious disease. Surgery is the most effective way to treat HAF. Dressing change is an indispensable part of the rehabilitation process after surgery. The purpose of this study is to provide feasibility and evidence of safety for the implementation of a simplified dressing change after loose combined cutting seton (LCCS) surgery and to offer a better method for clinical treatment and postoperative rehabilitation of HAF. METHODS: In this single-blind randomized controlled trial, 76 patients diagnosed with HAF will be randomly divided into two groups: the simplified dressing change group (n=38) or the traditional debridement and dressing change group (n=38). Compared with traditional debridement and dressing change, simplified dressing change was conducted without mechanical debridement and disinfection. All patients were treated surgically with the LCCS and dressing change. Postoperative follow-up will be carried out on the 3rd, 7th, 14th, 21st, and 180th day after the operation. The primary outcomes will be: complete healing rate of wound and fistula, long-term recurrence rate, poor wound healing rate, and complete wound healing time. The following secondary outcomes will be evaluated: postoperative pain using a visual analogue scale (VAS) score, wound secretions, edema, granulation shape, depth of wound, duration of each dressing change, and incidence of adverse events. DISCUSSION: Dressing change after HAF surgery is a necessary stage of recovery after anorectal surgery. Effective dressing change can reduce false healing and increase the cure rate. However, traditional dressing change takes a long time, and the patient endures severe pain. We have found that the dressing change process can be simplified in the clinic for patients treated with LCCS. In particular, simplification of the dressing change process may be related to the unobstructed drainage provided by the combination of LCCS and the separation of the dotted line. We will treat HAF using LCCS and compare the simplified dressing change method after the operation with traditional routine debridement and dressing change to demonstrate whether the simplified dressing change can be used in patients with HAF treated with LCCS. TRIAL REGISTRATION: ChiCTR2100047312.

Targeting the ubiquitination/deubiquitination process to regulate immune checkpoint pathways.

The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage, thus acting as a fortress of the body. However, excessive responses cause detrimental effects, such as inflammation and autoimmune diseases. To balance the immune responses and maintain immune homeostasis, there are immune checkpoints to terminate overwhelmed immune responses. Pathogens and tumor cells can also exploit immune checkpoint pathways to suppress immune responses, thus escaping immune surveillance. As a consequence, therapeutic antibodies that target immune checkpoints have made great breakthroughs, in particular for cancer treatment. While the overall efficacy of immune checkpoint blockade (ICB) is unsatisfactory since only a small group of patients benefited from ICB treatment. Hence, there is a strong need to search for other targets that improve the efficacy of ICB. Ubiquitination is a highly conserved process which participates in numerous biological activities, including innate and adaptive immunity. A growing body of evidence emphasizes the importance of ubiquitination and its reverse process, deubiquitination, on the regulation of immune responses, providing the rational of simultaneous targeting of immune checkpoints and ubiquitination/deubiquitination pathways to enhance the therapeutic efficacy. Our review will summarize the latest findings of ubiquitination/deubiquitination pathways for anti-tumor immunity, and discuss therapeutic significance of targeting ubiquitination/deubiquitination pathways in the future of immunotherapy.

A novel digital altered cast impression technique for fabricating a removable partial denture with a distal extension.

BACKGROUND: Although computer-aided design and computer-aided manufacturing has been successfully used in fabricating removable partial dentures (RPDs), making altered cast impressions is still a time-consuming and labor-intensive process for fabricating RPDs with a distal extension. An alternative digital technique has been developed to simplify this process. METHODS: The authors present a case in which they sought to improve the efficiency and simplicity in obtaining altered cast impressions by means of digital technology. Initially, a primary plaster cast was scanned as a digital cast. Based on the digital cast, a novel custom tray was designed and fabricated using a 3-dimensional printing method. With the custom tray, the novel altered cast impression was fabricated and scanned, and the final virtual altered cast was reconstructed by a stitching method. RESULTS: Based on the virtual altered cast, the authors designed the virtual RPD framework. Finally, the titanium alloy framework was fabricated using a 3-dimensional printing process, and the authors fit the final RPD to the patient. CONCLUSIONS: This novel digital altered cast impression technique may eliminate interoperator variability and increase precision compared with the traditional technique. PRACTICAL IMPLICATIONS: This technique showed the potential for reducing clinical appointments, chair time, and laboratory procedures.

Robustly Fitting and Forecasting Dynamical Data With Electromagnetically Coupled Artificial Neural Network: A Data Compression Method.

In this paper, a dynamical recurrent artificial neural network (ANN) is proposed and studied. Inspired from a recent research in neuroscience, we introduced nonsynaptic coupling to form a dynamical component of the network. We mathematically proved that, with adequate neurons provided, this dynamical ANN model is capable of approximating any continuous dynamic system with an arbitrarily small error in a limited time interval. Its extreme concise Jacobian matrix makes the local stability easy to control. We designed this ANN for fitting and forecasting dynamic data and obtained satisfied results in simulation. The fitting performance is also compared with those of both the classic dynamic ANN and the state-of-the-art models. Sufficient trials and the statistical results indicated that our model is superior to those have been compared. Moreover, we proposed a robust approximation problem, which asking the ANN to approximate a cluster of input-output data pairs in large ranges and to forecast the output of the system under previously unseen input. Our model and learning scheme proposed in this paper have successfully solved this problem, and through this, the approximation becomes much more robust and adaptive to noise, perturbation, and low-order harmonic wave. This approach is actually an efficient method for compressing massive external data of a dynamic system into the weight of the ANN.

FOXC1 in cancer development and therapy: deciphering its emerging and divergent roles.

Forkhead box C1 (FOXC1) is an essential member of the forkhead box transcription factors and has been highlighted as an important transcriptional regulator of crucial proteins associated with a wide variety of carcinomas. FOXC1 regulates tumor-associated genes and is regulated by multiple pathways that control its mRNA expression and protein activity. Aberrant FOXC1 expression is involved in diverse tumorigenic processes, such as abnormal cell proliferation, cancer stem cell maintenance, cancer migration, and angiogenesis. Herein, we review the correlation between the expression of FOXC1 and tumor behaviors. We also summarize the mechanisms of the regulation of FOXC1 expression and activity in physiological and pathological conditions. In particular, we focus on the pathological processes of cancer targeted by FOXC1 and discuss whether FOXC1 is good or detrimental during tumor progression. Moreover, FOXC1 is highlighted as a clinical biomarker for diagnosis or prognosis in various human cancers. The information reviewed here should assist in experimental designs and emphasize the potential of FOXC1 as a therapeutic target for cancer.

Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles.

Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet-induced obese mouse model to determine the effects of PTE on lipid accumulation. Next-generation sequencing analysis of liver gene expression and gut microbiota profiles following PTE treatment were conducted to elucidate possible mechanisms. We found that treatment of fully differentiated 3T3-L1 adipocytes with PTE inhibited lipid accumulation in the cells through reducing lipid formation and triglyceride content and by increasing lipase activity. No cytotoxicity was observed from the PTE treatment. After 5 weeks of treatment with PTE, the increased body weight, elevated serum triglyceride content, and liver steatosis in the high-fat diet-induced obese mice were each reduced. Liver transcriptomic analysis revealed that expression of genes involved in lipid and cholesterol metabolism was significantly altered. The low-grade chronic inflammation of obesity caused by a high-fat diet was also decreased after PTE treatment. In addition, treatment with PTE improved the relatively low Bacteroidetes/Firmicutes ratio in the gut of high-fat diet-fed mice through enrichment of the Proteobacteria population and reduction of the Deferribacteres population. In conclusion, treatment with PTE inhibited lipid accumulation by inducing the expression of the master transcription factor PPARα, attenuated the low-grade chronic inflammation of obesity, and also altered gut microbiota profiles. These results indicate that PTE has the potential to be developed into an anti-obesity food supplement and therapy. Abbreviations: Abcg5: ATP-binding cassette subfamily G member 5; ALT: alanine aminotransferase; AMPK: adenosine monophosphate-activated protein kinase; AST: aspartate aminotransferase; B/F: Bacteroidetes to Firmicutes [ratio]; C/EBPα: CCAAT/enhancer-binding protein alpha; CR: creatinine; Cyp51: cytochrome P450 family 51; DMEM: Dulbecco's modified Eagle's medium; Fabp5: fatty acid-binding protein 5; FBS: fetal bovine serum; Fdps: farnesyl diphosphate synthase; Glc: Glucose; HFD: high-fat diet; GO: gene ontology; HPRT: hypoxanthine guanine phosphoribosyl transferase; IBMS: 3-isobutyl-1-methylxanthine; Idi1: isopentenyl-diphosphate delta isomerase 1; IL-1ß: interleukin-1-beta; Lpin1: phosphatidic acid phosphohydrolase; LPS: lipopolysaccharide; Mvd: mevalonate diphosphate decarboxylase; ND: normal diet; OTU: operational taxonomic units; Pcsk9: proprotein convertase subtilisin/kexin 9; Pctp: phosphatidylcholine transfer protein; PPARα: peroxisome proliferator-activated receptor alpha; PPARγ: peroxisome proliferator-activated receptor gamma; PTE: Polygala tenuifolia extract; Saa1: serum amyloid A1; SD: standard deviation; SEM: standard error of the mean; Serpina12: serpin family member 12; Sqle: squalene monooxygenase; SREBP1C: sterol regulatory element-binding protein 1C; TCHO: total cholesterol; TG: triglyceride.

In vivo evaluation of an antibacterial coating containing halogenated furanone compound-loaded poly(l-lactic acid) nanoparticles on microarc-oxidized titanium implants.

To prevent peri-implant infection, a new antibacterial coating containing a halogenated furanone compound, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone-loaded poly(l-lactic acid) nanoparticles, has been fabricated. The current study was designed to evaluate the preventive effect of the antibacterial coating under a simulated environment of peri-implant infection in vivo. Microarc-oxidized titanium implants treated with minocycline hydrochloride ointment were used as positive control group, and microarc-oxidized titanium implants without any treatment were used as blank control group. Three kinds of implants were implanted in dogs' mandibles, and the peri-implant infection was simulated by silk ligation and feeding high sugar diet. After 2-month implantation, the results showed that no significant differences were detected between the experimental and positive control groups (P>0.05), but the data of clinical measurements of the blank control group were significantly higher than those of the other two groups (P<0.05), and the bone-implant contact rate and ultimate interfacial strength were significantly lower than those of the other two groups (P<0.05). Scanning electron microscope observation and histological examination showed that more new bone was formed on the surface of the experimental and positive control groups. It can be concluded that the antibacterial coating fabricated on implants has remarkable preventive effect on peri-implant infection at the early stage.