Retrospective study about clinical severity and epidemiological analysis of the COVID-19 Omicron subvariant lineage-infected patients in Hohhot, China.

BACKGROUND: Fear of a global public health issue and fresh infection wave in the persistent COVID-19 pandemic has been enflamed by the appearance of the novel variant Omicron BF.7 lineage. Recently, it has been seeing the novel Omicron subtype BF.7 lineage has sprawled exponentially in Hohhot. More than anything, risk stratification is significant to ascertain patients infected with COVID-19 who the most need in-hospital or in-home management. The study intends to understand the clinical severity and epidemiological characteristics of COVID-19 Omicron subvariant BF.7. lineage via gathering and analyzing the cases with Omicron subvariant in Hohhot, Inner Mongolia. METHODS: Based upon this, we linked variant Omicron BF.7 individual-level information including sex, age, symptom, underlying conditions and vaccination record. Further, we divided the cases into various groups and assessed the severity of patients according to the symptoms of patients with COVID-19. Clinical indicators and data might help to predict disadvantage outcomes and progression among Omicron BF.7 patients. RESULTS: In this study, in patients with severe symptoms, some indicators from real world data such as white blood cells, AST, ALT and CRE in patients with Omicron BF.7 in severe symptoms were significantly higher than mild and asymptomatic patients, while some indicators were significantly lower. CONCLUSIONS: Above results suggested that the indicators were associated with ponderance of clinical symptoms. Our survey emphasized the value of timely investigations of clinical data obtained by systemic study to acquire detailed information.

Cholestane-3ß,5α,6ß-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation.

Cholestane-3ß,5α,6ß-triol (CT) and its analogues are abundant in natural sources and are reported to demonstrate cytotoxicity toward different kinds of tumor cells without a deep probe into their mechanism of action. CT is also one of the major metabolic oxysterols of cholesterol in mammals and is found to accumulate in various diseases. An extensive exploration of the biological roles of CT over the past few decades has established its identity as an apoptosis inducer. In this study, the effects of CT on A549 cell death were investigated through cell viability assays. RNA-sequencing analysis and western blot of CT-treated A549 cells revealed the role of CT in inducing endoplasmic reticulum (ER) stress response and enhancing autophagy flux, suggesting a putative mechanism of CT-induced cell-death activation involving reactive oxygen species (ROS)-mediated ER stress and autophagy. It is reported for the first time that the upregulation of autophagy induced by CT can serve as a cellular cytotoxicity response in accelerating CT-induced cell death in A549 cells. This research provides evidence for the effect of CT as an oxysterol in cell response to oxidative damage and allows for a deep understanding of cholesterol in its response in an oxidative stress environment that commonly occurs in the progression of various diseases.

Hydroxysafflor yellow A protects against colitis in mice by suppressing pyroptosis via inhibiting HK1/NLRP3/GSDMD and modulating gut microbiota.

Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5'-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1ß, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.

Cyclometalated iridium(III) complexes induce immunogenic cell death in HepG2 cells via paraptosis.

Immunotherapy has been shown to provide superior antitumor efficacy by activating the innate immune system to recognize, attack and eliminate tumor cells without seriously harming normal cells. Herein, we designed and synthesized three new cyclometalated iridium(III) complexes (Ir1, Ir2, Ir3) then evaluated their antitumor activity. When co-incubated with HepG2 cells, the complex Ir1 localized in the lysosome, where it induced paraptosis and endoplasmic reticulum stress (ER stress). Notably, Ir1 also induced immunogenic cell death (ICD), promoted dendritic cell maturation that enhanced effector T cell chemotaxis to tumor tissues, down-regulated proportions of immunosuppressive regulatory T cells within tumor tissues and triggered activation of antitumor immunity throughout the body. To date, Ir1 is the first reported iridium(III) complex-based paraptosis inducer to successfully induce tumor cell ICD. Furthermore, Ir1 induced ICD of HepG2 cells without affecting cell cycle or reactive oxygen species levels.

Radiomics in the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor. At present, early diagnosis of HCC is difficult and therapeutic methods are limited. Radiomics can achieve accurate quantitative evaluation of the lesions without invasion, and has important value in the diagnosis and treatment of HCC. Radiomics features can predict the development of cancer in patients, serve as the basis for risk stratification of HCC patients, and help clinicians distinguish similar diseases, thus improving the diagnostic accuracy. Furthermore, the prediction of the treatment outcomes helps determine the treatment plan. Radiomics is also helpful in predicting the HCC recurrence, disease-free survival and overall survival. This review summarized the role of radiomics in the diagnosis, treatment and prognosis of HCC.

Factors affecting acceptance of organ donation in mainland China: A national cross-sectional study.

AIMS AND OBJECTIVES: To explore the acceptances and associated influences of organ donation in mainland China. BACKGROUND: The shortage of organ donors has limited the development of organ transplantation in China. It is important to recognise the target population who has high intention to donate their organs may change the status. DESIGN: We conducted a cross-sectional, multi-stage sampling study collected demographic data and individuals' willingness to accept organ donation. METHODS: A stepwise linear regression analysis was adopted to evaluate the factors related to the attitudes toward organ donation. RESULTS: We collected 11,031 valid samples for the survey. The willingness to donate organs among Chinese residents averaged 56.93 points. To be specific, males (ß = -.03), religious believers (ß = -.01) and parents with a different number of children (all: ß = -.04) are less willing to donate their organs. Respondents who live in an urban area (ß = .03), have higher education level (High school or junior college ß = .04, Bachelor degree or above ß = .09), feel anxious (mild, moderate ß = .02), feel pressured (moderate, severe ß = .08), have higher scores of the Short-Form Health Literacy Instrument (HLS-SF12) (ß = .31), The Self-Management Scale (SHMS) (ß = .16), EuroQol Five Dimensions Questionnaire (EQ-5D) (ß = .04) and EuroQol Visual Analogue Scale (EQ-VAS) (ß = .24), are more positive to donate. CONCLUSIONS: This study firstly discusses the public acceptance of organ donation through a nationwide sample around China. In this study, we discovered that Chinese residents' acceptance level of organ donation and that gender, house, anxiety, pressure, social support and health literacy were the main influencing factors on residents' attitudes. RELEVANCE TO CLINICAL PRACTICE: To figure out the Chinese public acceptance and its influencing factors of organ donation can help nurse transplant coordinators to recognise the target population and the obstacles of organ donation. PATIENT OR PUBLIC CONTRIBUTION: At the phase of collecting data, participants were recruited to fill the questionnaires.

Treatment of Cutaneous Balamuthia mandrillaris Infection With Diminazene Aceturate: A Report of 4 Cases.

Four cases of cutaneous Balamuthia mandrillaris infection were treated with diminazene aceturate. One patient was cured with mainly monotherapy, 2 patients were cured with diminazene aceturate and excision, and 1 patient died of drug-induced liver damage. This is the first report of B. mandrillaris infection treated with diminazene aceturate.

ABI2-mediated MEOX2/KLF4-NANOG axis promotes liver cancer stem cell and drives tumour recurrence.

Tumour recurrence and drug resistance in hepatocellular carcinoma remain challenging. Cancer stem cells (CSCs) are responsible for tumour initiation because of their stemness characteristics. CSCs accounting for drug resistance and tumour relapse are promising therapeutic targets. We report that Abelson interactor 2 (ABI2) is a novel therapeutic target of HCC CSCs. First, ABI2 was upregulated in HCC tissues compared with liver tissues and was associated with tumour size, pathological grade, liver cirrhosis, worse prognosis and a high recurrence rate. Functional studies illustrate that ABI2 knockdown suppresses cell growth, migration, invasion and sorafenib resistance in vitro. Furthermore, ABI2 knockdown inhibited HCC sphere formation and decreased the CD24+ , CD133+ and CD326+ CSCs populations, suggesting the suppression of HCC stemness characteristics. A tumour xenograft model and limiting dilution assay demonstrated the inhibition of tumorigenicity and tumour initiation. Moreover, molecular mechanism studies showed that ABI2 recruits and directly interacts with the transcription factor MEOX2, which binds to the KLF4 and NANOG promoter regions to activate their transcription. Furthermore, overexpression of MEOX2 restored HCC malignant behaviour and the CSC population. The ABI2-mediated transcriptional axis MEOX2/KLF4-NANOG promotes HCC growth, metastasis and sorafenib resistance by maintaining the CSC population, suggesting that ABI2 is a promising CSC target in HCC treatment.

Regulation effect of miR-7 on intervening colorectal cancer rats with HP infection through Akt/GSK-3ß/ß-catenin pathway.

This experiment aimed to analysis of the intervention effects of modulating miR-7 on rats with colorectal cancer complicated with HP infection and the effects on (serine/threonine kinase) Akt / (glycogen synthase kinase 3 ß） GSK-3 ß/ （ ß- ß - Catenin) ß- Influence of the catenin pathway. For this purpose, forty special pathogen-free (SPF) - grade rats of both sexes were randomly divided into 10 control, 10 colorectal cancer and HP infection model groups, 10 up-regulated miR-7, and 10 down-regulated miR-7 groups. Observational analysis of rat colon tissues was performed using the HE staining method. Detection of inflammatory factors [TNF- α、 IL-8, IL-6], detection of miR-7 expression, detection of Akt, GSK-3 using Western blot ß、ß- Catenin protein expression. Results showed that forty special pathogen-free (SPF) - grade rats of both sexes were randomly divided into 10 control, 10 colorectal cancer and HP infection model groups, 10 up-regulated miR-7, and 10 down-regulated miR-7 groups. Observational analysis of rat colon tissues was performed using the HE staining method. Detection of inflammatory factors [TNF- α、 IL-8, IL-6], detection of miR-7 expression, detection of Akt, GSK-3 using Western blot ß、ß- Catenin protein expression. It was concluded that modulation of miR-7 in rats with colorectal cancer and HP infection enables regulation of the Akt / GSK-3 ß/ß- Catenin pathway to improve serum inflammation condition and alleviate HP infection in rats, which played a better role in intervention.

Visible-Light-Mediated Oxidative Cyclization of 2-Aminobenzyl Alcohols and Secondary Alcohols Enabled by an Organic Photocatalyst.

This paper describes a visible-light-mediated oxidative cyclization of 2-aminobenzyl alcohols and secondary alcohols to produce quinolines at room temperature. This photocatalytic method employed anthraquinone as an organic small-molecule catalyst and DMSO as an oxidant. According to this present procedure, a series of quinolines were prepared in satisfactory yields.

Methyl-CpG-binding domain 3 inhibits stemness of pancreatic cancer cells via Hippo signaling.

Methyl-CpG-binding domain 3 (MBD3), as an induced stem cells reprogramming barrier, has an abnormal expression in various prevalent malignancies. However, in pancreatic cancer cell stemness, the roles of MBD3 remain unclear. In our study, the effects of MBD3 were investigated on the proliferation, stemness and the underlying mechanism in pancreatic cancer cells. Firstly, MBD3 knockdown was proved to promote proliferation and sphere formation of pancreatic cancer cells and tumorigenesis, while MBD3 upregulation inhibited the above results. Also, MBD3 downregulation notably increased stemness markers level of OCT4, NANOG and SOX2, and MBD3 upregulation resulted in the opposite effects. Mechanically, it was found that MBD3 involved in activation of Hippo pathway. There was a negative correlation between MBD3 and YAP expression in TCGA database. MBD3 knockdown improved YAP expression, and promoted YAP nuclear translocation increased TEAD luciferase activity, while MBD3 overexpression reversed the above results. Further evidence revealed that YAP could bind to MBD3, and decreased MBD3 expression. Collectively, MBD3 bound to YAP to significantly inhibit proliferation and weaken stemness maintenance in pancreatic cancer cells, as well as reduce tumorigenesis via Hippo signaling. Thus, MBD3 may serve as a potential molecular biomarker for exploring new therapeutic strategies to treat pancreatic cancer.

Mitochondria-targeted Re(I) complexes bearing guanidinium as ligands and their anticancer activity.

As the "powerhouse" of a cell, mitochondria maintain energy homeostasis, synthesize ATP via oxidative phosphorylation, generate ROS signaling molecules, and modulate cell apoptosis. Herein, three Re(I) complexes bearing guanidinium derivatives have been synthesized and characterized. All of these complexes exhibit moderate anticancer activity in HepG2, HeLa, MCF-7, and A549 cancer cells. Mechanism studies indicate that complex 3, [Re(CO)3(L)(Im)](PF6)2, can selectively localize in the mitochondria and induce cancer cell death through mitochondria-associated pathways. In addition, complex 3 can effectively depress the ability of cell migration, cell invasion, and colony formation.

Homocysteine induces melanocytes apoptosis via PERK-eIF2α-CHOP pathway in vitiligo.

Vitiligo is a depigmentation disorder that develops as a result of the progressive disappearance of epidermal melanocytes. The elevated level of amino acid metabolite homocysteine (Hcy) has been identified as circulating marker of oxidative stress and known as a risk factor for vitiligo. However, the mechanism underlying Hcy-regulated melanocytic destruction is currently unknown. The present study aims to elucidate the effect of Hcy on melanocytic destruction and its involvement in the pathogenesis of vitiligo. Our results showed that Hcy level was significantly elevated in the serum of progressive vitiligo patients. Notably, Hcy induced cell apoptosis in melanocytes via activating reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-C/EBP homologous protein (CHOP) pathway. More importantly, folic acid, functioning in the transformation of Hcy, could lower the intracellular Hcy level and further reverse the apoptotic effect of Hcy on melanocytes. Additionally, Hcy disrupted melanogenesis whereas folic acid supplementation could reverse the melanogenesis defect induced by Hcy in melanocytes. Taken together, Hcy is highly increased in vitiligo patients at progressive stage, and our in vitro studies revealed that folic acid could protect melanocytes from Hcy-induced apoptosis and melanin synthesis inhibition, indicating folic acid as a potential benefit agent for patients with progressive vitiligo.

Mechanistic Investigation of a Self-Assembling Peptide against Escherichia coli.

Because of their distinctive mode of action in targeting bacterial cell membranes, antimicrobial peptides (AMPs) are increasingly regarded as a potential candidate for the development of novel antibiotics to combat the wide spread of bacterial resistance. To date, understanding of the exact molecular process by which AMPs act on the real bacterial envelope remains challenging. Simultaneously, the aggregated state of AMPs upon interaction with bacterial envelopes is still elusive. Previously, we have demonstrated that the potent antibacterial activity of a designed surfactant-like peptide Ac-A9K-NH2 benefited greatly from its high self-assembling ability and appropriate self-assembled morphologies and sizes. By using high-resolution atomic force microscopy, we here not only follow the variations of the Escherichia coli cell envelope in the presence of Ac-A9K-NH2 but also characterize the peptide aggregates on the bacterial surface as well as on the substrate surface. The results, together with those from fluorescence, zeta potential, circular dichroism, and scanning electron microscopy measurements, indicate that both the positively charged peptide monomers and self-assembled nanostructures can directly act on the negatively charged bacterial surface, followed by their insertion into the bacterial membrane, the formation of surface nanopores, and membrane lysis. The mechanism of Ac-A9K-NH2 against E. coli is thus consistent with the detergent-like mode of action. This work enhances our mechanistic understanding of the antibacterial behaviors of self-assembling peptides that will be valuable in exploring their biomedical applications.

Effects of salts on the self-assembly behavior and antibacterial activity of a surfactant-like peptide.

Self-assembling peptides have become one of the most promising antibacterial agents due to their superior properties, such as simple molecular composition, favorable assembly structures, and rich designability. For maximum application in vivo, their activities in the presence of salts are desirable, however, the potent correlation between peptide nanostructures, antibacterial activity, and salt resistance behavior remains poorly explored. Previously, we have demonstrated that the potent antibacterial activity of a designed surfactant-like peptide Ac-A9K-NH2 benefited from its high self-assembly ability and appropriate size of its self-assembled nanostructures. In this study, we investigated the effect of salts on its self-assembly behavior and antibacterial activity. The results indicated that the flexible and long nanofibrils formed by Ac-A9K-NH2 in the presence of CaCl2 were adverse to its membrane insertion, leading to the reduction of antibacterial activity. Comparatively, Ac-A9K-NH2 maintained its potent antibacterial activity in the presence of NaCl due to its suitable shape and size of nanostructures. The newly formed nanofibers and nanorods facilitated the penetration of peptides into the bacterial membrane, forming nanopores and eventually leading to the lysis of bacteria. The high antibacterial activity and NaCl tolerance of Ac-A9K-NH2 make it a promising antibacterial agent at elevated salt concentrations.

Large electrostrain induced by reversible domain switching in ordered ferroelectric nanostructures with optimized geometric configurations.

Large electromechanical response of ferroelectric materials is particularly appealing for applications in functional devices, such as sensors and actuators. For conventional ferroelectric materials, however, the mechanical strain under an external electric field, i.e. the electrostrain, is often limited by the intrinsic electromechanical property of the materials. Domain engineering has been suggested as a practical way to overcome this limitation and to enhance the electrostrain. Here, we show from phase-field simulations that reversible domain switching in ordered ferroelectric nanostructures with optimized geometric configurations can enhance the electrostrain significantly. In the presence of an external electric field, the domains in such nanostructures can switch from a multi-domain state confined by the geometric configurations to a mono-domain state. It is interesting that the domains can switch back to the multi-domain state due to strong internal depolarization fields once the electric field is removed. As a result, accompanying the reversible domain switching behavior, a large and reversible electrostrain can be obtained. Going further, it is found that the temperature dependence of the large electrostrain is similar to that of polarization in such nanostructures. The present work opens a perspective to obtaining large electrostrain in nanoscale ferroelectrics, which holds great promise for designing electromechanical functional devices with high performance.

Preferential Localization of MUC1 Glycoprotein in Exosomes Secreted by Non-Small Cell Lung Carcinoma Cells.

Lung cancer remains to be the leading cause of cancer-related mortality worldwide. Finding new noninvasive biomarkers for lung cancer is still a significant clinical challenge. Exosomes are membrane-bound, nano-sized vesicles that are released by various living cells. Studies on exosomal proteomics may provide clues for developing clinical assays. In this study, we performed semi-quantitative proteomic analysis of proteins that were purified from exosomes of NCI-H838 non-small cell lung cancer cell line, with total cellular membrane proteins as control. In the exosomes, LC-MS/MS by data-independent analysis mode identified 3235 proteins. THBS1, ANXA6, HIST1H4A, COL18A1, MDK, SRGN, ENO1, TUBA4A, SLC3A2, GPI, MIF, MUC1, TALDO1, SLC7A5, ICAM1, HSP90AA1, G6PD, and LRP1 were found to be expressed in exosomes at more than 5-fold higher level as compared to total cellular membrane proteins. A well-known cancer biomarker, MUC1, is expressed at 8.98-fold higher in exosomes than total cellular membrane proteins. Subsequent analysis of plasma exosomes from non-small cell lung cancer (NSCLC) patients by a commercial electrochemiluminescence immunoassay showed that exosomal MUC1 level is 1.5-fold higher than healthy individuals (mean value 1.55 ± 0.16 versus mean value 1.05 ± 0.06, p = 0.0213). In contrast, no significant difference of MUC1 level was found between NSCLC patients and healthy individuals' plasma (mean value 5.48 ± 0.65 versus mean value 4.16 ± 0.49). These results suggest that certain proteins, such as MUC1, are selectively enriched in the exosome compartment. The mechanisms for their preferential localization and their biological roles remain to be studied.

Identification of the Risk HLA-A Alleles and Autoantigen in Han Chinese Vitiligo Patients and the Association of CD8+T Cell Reactivity with Disease Characteristics.

BACKGROUND Multiple studies have implicated a role for CD8+T cell-mediated immune response to autoantigens in vitiligo. However, the antigen-specific T lymphocyte reactivity against the peptide epitopes is diverse among different world populations. This study aimed to identify the risk HLA-A allele in vitiligo and study CD8+ T cell reactivity to 5 autoantigenic peptides in Han Chinese populations, and to analyze the association of CD8+ T cell reactivity with disease characteristics. MATERIAL AND METHODS The risk HLA-A allele was analyzed by case-control study. Enzyme linked immunospot (ELISPOT) assay was used to compare T cell reactivity to the 5 autoantigenic peptides between vitiligo patients and healthy controls, then we analyzed the association of CD8+ T cell reactivity to 2 positive peptides with disease activity and area of skin lesions. RESULTS The results indicated that the most frequent allele in the Han Chinese vitiligo patients was the HLA-A*02: 01 allele with a significantly higher frequency compared to controls (20.20% versus 13.79%, P=6.64×10-5). The most frequently encountered epitopes were 2 gp100 modified peptides, IMDQVPFSV and YLEPGPVTV, whereas a weak T cell reactivity against tyrosinase and Melan-A/MART-1 were evaluated. Moreover, we demonstrated that T cell reactivity against the 2 positive peptides was significantly associated with disease characteristics including disease activity and area of skin lesions. CONCLUSIONS Our findings showed that the HLA-A*02: 01 allele was the major risk HLA-A allele, and 2 gp100 modified peptides were identified as autoantigens and were found to be closely related to disease characteristics which might play a critical role in Han Chinese vitiligo patients.

Effect of titanium ions on the Hippo/YAP signaling pathway in regulating biological behaviors of MC3T3-E1 osteoblasts.

Titanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long-term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear. Hippo signaling has been confirmed to be involved in organ size and tissue regeneration in many organs, while its roles in osteoblasts differentiation and bone repair remained elusive. Therefore, we hypothesize that YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal development and bone repair, as well as excessive Ti ions promoted the progression of YAP activation. This study aimed to explore the role of Hippo/YAP signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors. Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient previously reported that was capable of suppressing osteoblasts growth, induced nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion-induced YAP activation was found to downregulate osteogenic differentiation of MC3T3-E1 cells. Most importantly, the hypothesis we proposed that knockdown of YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been verified. Taken together, our work provides insights into the mechanism of which YAP is involved in regulating osteoblast behaviors under the effect of Ti ions, which may help to develop therapeutic applications for Ti implant failures and peri-implantitis.

Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis.

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.