GATA6-AS1 via Sponging miR-543 to Regulate PTEN/AKT Signaling Axis Suppresses Cell Proliferation and Migration in Gastric Cancer.

Gastric cancer (GC) is one of the most common and lethal cancers worldwide. In view of the prominent roles of long noncoding RNAs (lncRNAs) in cancers, we investigated the specific role and underlying mechanism of GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in GC. Quantitative real-time polymerase chain reaction (qRT-PCR) detected GATA6-AS1 expression in GC cell lines. Functional assays were conducted to explore the role of GATA6-AS1 in GC. Furthermore, mechanism investigations were implemented to uncover the interaction among GATA6-AS1, microRNA-543 (miR-543), and phosphatase and tensin homolog (PTEN). In the present study, it was found that GATA6-AS1 expression is significantly downregulated in GC cell lines. Functionally, GATA6-AS1 markedly suppresses GC cell growth and migration in vitro and in vivo tumorigenesis. Besides tumor suppressor, GATA6-AS1 serves as a miR-543 sponge. Specifically speaking, GATA6-AS1 acts as a competing endogenous RNA (ceRNA) of miR-543 to upregulate the expression of PTEN, thus inactivating AKT signaling pathway to inhibit GC progression. In conclusion, this study has manifested that GATA6-AS1 inhibits GC cell proliferation and migration as a sponge of miR-543 by regulating PTEN/AKT signaling axis, offering new perspective into developing novel GC therapies.

Stationary distribution and probability density for a stochastic SEIR-type model of coronavirus (COVID-19) with asymptomatic carriers.

In this paper, we propose a stochastic SEIR-type model with asymptomatic carriers to describe the propagation mechanism of coronavirus (COVID-19) in the population. Firstly, we show that there exists a unique global positive solution of the stochastic system with any positive initial value. Then we adopt a stochastic Lyapunov function method to establish sufficient conditions for the existence and uniqueness of an ergodic stationary distribution of positive solutions to the stochastic model. Especially, under the same conditions as the existence of a stationary distribution, we obtain the specific form of the probability density around the quasi-endemic equilibrium of the stochastic system. Finally, numerical simulations are introduced to validate the theoretical findings.

Expression of KIF2A, NDC80, CDK1, and CCNB1 in breast cancer patients: Their interaction and linkage with tumor features and prognosis.

BACKGROUND: Kinesin family member 2A (KIF2A), nuclear division cycle 80 (NDC80), cyclin-dependent kinase 1 (CDK1), and cyclin B1 (CCNB1) exhibit a complex interrelation, which promote cancer progression via multiple ways, whereas their interaction and clinical implications in breast cancer are obscure. Hence, this study aimed to evaluate the correlation among KIF2A, NDC80, CDK1, CCNB1, and their linkage with clinicopathological features and prognosis in breast cancer patients. METHODS: 195 breast cancer patients underwent surgical resection were analyzed. KIF2A, NDC80, CDK1, and CCNB1 expressions were determined by immunohistochemical (IHC) assay and scored by a semiquantitative IHC score or positive cell percentage. RESULTS: KIF2A expression positively associated with NDC80, CDK1, and CCNB1 expressions (all p < 0.01). In terms of tumor features: KIF2A high expression linked with increased T stage (p = 0.011), N stage (p = 0.014), and TNM stage (p = 0.009) but not tumor differentiation (p = 0.651). NDC80 high expression only related to higher N stage (p = 0.010); CDK1 high expression only connected with elevated N stage (p = 0.035) and TNM stage (p = 0.023). In aspect of prognosis, high expression of KIF2A was correlated with worse disease-free survival (DFS) (p = 0.031), while NDC80 high (p = 0.329), CDK1 high (p = 0.276), and CCNB1 positive (p = 0.063) expressions only showed trends to link with poor DFS (without statistical significance). Furthermore, high expression of KIF2A (p = 0.063), NDC80 (p = 0.939), CDK1 (p = 0.413) and positive expression of CCNB1 (p = 0.296) did not relate to overall survival. CONCLUSION: KIF2A correlates with NDC80, CDK1, CCNB1, and may link with advanced tumor stages and poor prognosis in breast cancer patients.

Asymptotic behavior of a stochastic SIR model with general incidence rate and nonlinear Lévy jumps.

In this paper, we consider a stochastic SIR epidemic model with general disease incidence rate and perturbation caused by nonlinear white noise and L e ´ vy jumps. First of all, we study the existence and uniqueness of the global positive solution of the model. Then, we establish a threshold λ by investigating the one-dimensional model to determine the extinction and persistence of the disease. To verify the model has an ergodic stationary distribution, we adopt a new method which can obtain the sufficient and almost necessary conditions for the extinction and persistence of the disease. Finally, some numerical simulations are carried out to illustrate our theoretical results.

Stationary distribution and probability density function of a stochastic SVIS epidemic model with standard incidence and vaccination strategies.

Considering the great effect of vaccination and the unpredictability of environmental variations in nature, a stochastic Susceptible-Vaccinated-Infected-Susceptible (SVIS) epidemic model with standard incidence and vaccination strategies is the focus of the present study. By constructing a series of appropriate Lyapunov functions, the sufficient criterion R 0 s > 1 is obtained for the existence and uniqueness of the ergodic stationary distribution of the model. In epidemiology, the existence of a stationary distribution indicates that the disease will be persistent in a long term. By taking the stochasticity into account, a quasi-endemic equilibrium related to the endemic equilibrium of the deterministic system is defined. By means of the method developed in solving the general three-dimensional Fokker-Planck equation, the exact expression of the probability density function of the stochastic model around the quasi-endemic equilibrium is derived, which is the key aim of the present paper. In statistical significance, the explicit density function can reflect all dynamical properties of an epidemic system. Next, a simple result of disease extinction is obtained. In addition, several numerical simulations and parameter analyses are performed to illustrate the theoretical results. Finally, the corresponding results and conclusions are discussed at the end of the paper.

Stationary distribution and density function expression for a stochastic SIQRS epidemic model with temporary immunity.

Recently, considering the temporary immunity of individuals who have recovered from certain infectious diseases, Liu et al. (Phys A Stat Mech Appl 551:124152, 2020) proposed and studied a stochastic susceptible-infected-recovered-susceptible model with logistic growth. For a more realistic situation, the effects of quarantine strategies and stochasticity should be taken into account. Hence, our paper focuses on a stochastic susceptible-infected-quarantined-recovered-susceptible epidemic model with temporary immunity. First, by means of the Khas'minskii theory and Lyapunov function approach, we construct a critical value R 0 S corresponding to the basic reproduction number R 0 of the deterministic system. Moreover, we prove that there is a unique ergodic stationary distribution if R 0 S > 1 . Focusing on the results of Zhou et al. (Chaos Soliton Fractals 137:109865, 2020), we develop some suitable solving theories for the general four-dimensional Fokker-Planck equation. The key aim of the present study is to obtain the explicit density function expression of the stationary distribution under R 0 S > 1 . It should be noted that the existence of an ergodic stationary distribution together with the unique exact probability density function can reveal all the dynamical properties of disease persistence in both epidemiological and statistical aspects. Next, some numerical simulations together with parameter analyses are shown to support our theoretical results. Last, through comparison with other articles, results are discussed and the main conclusions are highlighted.

Stationary distribution and extinction of a stochastic staged progression AIDS model with staged treatment and second-order perturbation.

Focusing on deterministic AIDS model proposed by Hyman (2000) and the detailed data from the World Health Organization (WHO), there are three stages of AIDS process which are described as Acute infection period, Asymptomatic phase and AIDS stage. Our paper is therefore concerned with a stochastic staged progression AIDS model with staged treatment. In view of the complexity of random disturbances, we reasonably take second-order perturbation into consideration for realistic sense. By means of our creative transformation technique and stochastic Lyapunov method, a critical value R 0 H > 1 is firstly obtained for the existence and uniqueness of ergodic stationary distribution to the stochastic system. Not only does it respectively reveal the corresponding dynamical effects of the linear and second-order perturbations to the model, but the unified form of second-order and linear fluctuations is derived. Next, some sufficient conditions about extinction of stochastic system are established in view of the basic reproduction number R 0 . Finally, some examples and numerical simulations are introduced to illustrate our analytical results. In addition, some advantages of our new method and theory are highlighted by comparison with other existing results at the end of this paper.

Dynamical behavior of a higher order stochastically perturbed SIRI epidemic model with relapse and media coverage.

This paper is intended to explore a higher order stochastically perturbed SIRI epidemic model with relapse and media coverage. Firstly, we derive sufficient criteria for the existence and uniqueness of an ergodic stationary distribution of positive solutions to the system by establishing a suitable stochastic Lyapunov function. Then we obtain adequate conditions for complete eradication and wiping out of the infectious disease. In a biological interpretation, the existence of a stationary distribution implies that the disease will prevail and persist in the long term. Finally, the theoretical results are illustrated by computer simulations, including two examples based on real-life disease.

Simultaneous determination and pharmacokinetic study of three flavonoid glycosides in rat plasma by LC-MS/MS after oral administration of Rubus chingii Hu extract.

A simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of isoquercitrin, kaempferol-3-O-rutinoside and tiliroside in rat plasma. Plasma samples were deproteinized with methanol and separated on a Hypersil Gold C18 column (2.1 × 50 mm, i.d., 3.0 µm) using gradient elution with the mobile phase of water and methanol at a flow rate of 0.4 mL/min. Mass spectrometric detection was performed with negative ion electrospray ionization in selected reaction monitoring mode. All analytes showed good linearity over their investigated concentration ranges (r2 > 0.99). The lower limit of quantification was 1.0 ng/mL for isoquercitrin and 2.0 ng/mL for kaempferol-3-O-rutinoside and tiliroside, respectively. Intra- and inter-day precisions were <8.2% and accuracy ranged from -11.5 to 9.7%. The mean extraction recoveries of analytes and IS from rat plasma were >80.4%. The assay was successfully applied to investigate the pharmacokinetic study of the three ingredients after oral administration of Rubus chingii Hu to rats.

Stationary distribution of a stochastic SIS epidemic model with double diseases and the Beddington-DeAngelis incidence.

In this paper, a stochastic Susceptible-Infected-Susceptible (SIS) epidemic model with double diseases and the Beddington-DeAngelis incidence is proposed and studied. Sufficient conditions for the existence of an ergodic stationary distribution of the positive solutions to the model are obtained via the Lyapunov function method. The existence of stationary distribution implies stochastic stability to some extent.

Docetaxel modulates the delayed rectifier potassium current (IK) and ATP-sensitive potassium current (IKATP) in human breast cancer cells.

Ion channel expression and activity may be affected during tumor development and cancer growth. Activation of potassium (K(+)) channels in human breast cancer cells is reported to be involved in cell cycle progression. In this study, we investigated the effects of docetaxel on the delayed rectifier potassium current (I K) and the ATP-sensitive potassium current (I KATP) in two human breast cancer cell lines, MCF-7 and MDA-MB-435S, using the whole-cell patch-clamp technique. Our results show that docetaxel inhibited the I K and I KATP in both cell lines in a dose-dependent manner. Compared with the control at a potential of +60 mV, treatment with docetaxel at doses of 0.1, 1, 5, and 10 µM significantly decreased the I K in MCF-7 cells by 16.1 ± 3.5, 30.2 ± 5.2, 42.5 ± 4.3, and 46.4 ± 9% (n = 5, P < 0.05), respectively and also decreased the I KATP at +50 mV. Similar results were observed in MDA-MB-435S cells. The G-V curves showed no significant changes after treatment of either MCF-7 or MDA-MB-435S cells with 10 µM docetaxel. The datas indicate that the possible mechanisms of I K and I KATP inhibition by docetaxel may be responsible for its effect on the proliferation of human breast cancer cells.

Clinicopathological and prognostic significance of FOXP3+ tumor infiltrating lymphocytes in patients with breast cancer: a meta-analysis.

BACKGROUND: The prognostic significance of FOXP3+ tumor-infiltrating lymphocytes (TILs) in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic significance in patients with breast cancer. METHODS: PubMed, Embase, Cochrane Database and the Ovid Database were systematically searched (up to April 2015). The meta-analysis was performed using hazard ratio (HR), odds ratio (OR) and 95 % confidence intervals (CI) as effect measures. Using the random-effects model, statistical analysis was performed using Stata software, version 12.0. RESULTS: Seventeen studies including 8277 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of FOXP3+ TILs was significant when comparing the lymph node positive group to negative group (OR = 1.305, 95 % CI [1.071, 1.590]), the histological grade III group to the I-II group (OR = 3.067, 95 % CI [2.288, 4.111]), the ER positive group to the negative group (OR = 0.435, 95 % CI [0.287, 0.660]), the PR positive group to the negative group (OR = 0.493, 95 % CI [0.296, 0.822]), the HER2 positive group to the negative group (OR = 1.896, 95 % CI [1.335, 2.692]), the TNBC group to the non TNBC group (OR = 2.456, 95 % CI [1.801, 3.348]). The detection of FOXP3+ TILs was significantly correlated with the recurrence-free survival (RFS) of patients (HR = 1.752, 95 % CI [1.188-2.584]) and the overall survival (OS) of patients (HR =1.447, 95 % CI [1.037-2.019]). CONCLUSIONS: Our meta-analysis demonstrates that the presence of high levels of FOXP3+ TILs is associated with prognosis for breast cancer patients and predicts lymph node metastasis, hormone receptor and HER-2 status.

Dynamic behaviors of a stochastic virus infection model with Beddington-DeAngelis incidence function, eclipse-stage and Ornstein-Uhlenbeck process.

In this paper, we present a virus infection model that incorporates eclipse-stage and Beddington-DeAngelis function, along with perturbation in infection rate using logarithmic Ornstein-Uhlenbeck process. Rigorous analysis demonstrates that the stochastic model has a unique global solution. Through construction of appropriate Lyapunov functions and a compact set, combined with the strong law of numbers and Fatou's lemma, we obtain the existence of the stationary distribution under a critical condition, which indicates the long-term persistence of T-cells and virions. Moreover, a precise probability density function is derived around the quasi-equilibrium of the model, and spectral radius analysis is employed to identify critical condition for elimination of the virus. Finally, numerical simulations are presented to validate theoretical results, and the impact of some key parameters such as the speed of reversion, volatility intensity and mean infection rate are investigated.

Stochastic modeling of SIS epidemics with logarithmic Ornstein-Uhlenbeck process and generalized nonlinear incidence.

In this paper, we investigate a stochastic SIS epidemic model with logarithmic Ornstein-Uhlenbeck process and generalized nonlinear incidence. Our study focuses on the construction of stochastic Lyapunov functions to establish the threshold condition for the extinction and the existence of the stationary distribution of the stochastic system. We also derive the exact expression of the density function around the quasi-endemic equilibrium, which provides valuable insight into the transmission and progression of the disease within a population. Our findings demonstrate the importance of considering the impact of stochasticity on the spread of epidemics, particularly in the presence of complex incidence mechanisms and stochastic environmental factors. Additionally, the stochastic threshold reveals that ordinary differential equation models and white noise models underestimate the severity of disease outbreaks, while our proposed the stochastic epidemic model with logarithmic Ornstein-Uhlenbeck process accurately captures real-world scenarios.

Analysis of Stochastic SIRC Model with Cross Immunity Based on Ornstein-Uhlenbeck Process.

In this paper, we analyze a stochastic SIRC model with Ornstein-Uhlenbeck process. Firstly, we give the existence and uniqueness of global solution of stochastic SIRC model and prove it. In addition, the existence of ergodic stationary distributions for stochastic SIRC system is proved by constructing a suitable series of Lyapunov functions. A quasi-endemic equilibrium related to endemic equilibrium of deterministic systems is defined by considering randomness. And we obtain the probability density function of the linearized system near the equilibrium point. After the proof of probability density function, the sufficient condition of disease extinction is given and proved. We prove the theoretical results in the paper by numerical simulation at the end of the paper.

Hypoxia-mediated activation of hypoxia-inducible factor-1α in triple-negative breast cancer: A review.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia-inducible factor 1α (HIF-1α) as a key hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, BC stem cells enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. This article discusses the expression of the HIF-1α transcription factor in TNBC and the Hypoxia-mediated activation of hypoxia-inducible factor-1α in triple-negative BC. It offers a fresh approach to clinical research and treatment for TNBC.

Research progress of exosomes in drug resistance of breast cancer.

Since breast cancer is a heterogeneous disease, there are currently a variety of treatment methods available, including chemotherapy, endocrine therapy, molecular targeted therapy, immunotherapy, radiation therapy, etc. Breast cancer recurrence and metastasis, despite many treatment modalities, constitute a considerable threat to patients' survival time and pose a clinical challenge that is difficult to tackle precisely. Exosomes have a very special and crucial role in the treatment of drug resistance in breast cancer as a carrier of intercellular communication in the tumor microenvironment. Exosomes and breast cancer treatment resistance have been linked in a growing number of clinical investigations in recent years. This paper covers the status of research on exosomes in the treatment of breast cancer drug resistance and offers theoretical guidance for investigating new strategies to treat breast cancer drug resistance.

3D bioprinting of dECM/Gel/QCS/nHAp hybrid scaffolds laden with mesenchymal stem cell-derived exosomes to improve angiogenesis and osteogenesis.

Craniofacial bone regeneration is a coupled process of angiogenesis and osteogenesis, which, associated with infection, still remains a challenge in bone defects after trauma or tumor resection. 3D tissue engineering scaffolds with multifunctional-therapeutic properties can offer many advantages for the angiogenesis and osteogenesis of infected bone defects. Hence, in the present study, a microchannel networks-enriched 3D hybrid scaffold composed of decellularized extracellular matrix (dECM), gelatin (Gel), quaterinized chitosan (QCS) and nano-hydroxyapatite (nHAp) (dGQH) was fabricated by an extrusion 3D bioprinting technology. And enlightened by the characteristics of natural bone microstructure and the demands of vascularized bone regeneration, the exosomes (Exos) isolated from human adipose derived stem cells as angiogenic and osteogenic factors were then co-loaded into the desired dGQH20hybrid scaffold based on an electrostatic interaction. The results of the hybrid scaffolds performance characterization showed that these hybrid scaffolds exhibited an interconnected pore structure and appropriate degradability (>61% after 8 weeks of treatment), and the dGQH20hybrid scaffold displayed the highest porosity (83.93 ± 7.38%) and mechanical properties (tensile modulus: 62.68 ± 10.29 MPa, compressive modulus: 16.22 ± 3.61 MPa) among the dGQH hybrid scaffolds. Moreover, the dGQH20hybrid scaffold presented good antibacterial activities (against 94.90 ± 2.44% ofEscherichia coliand 95.41 ± 2.65% ofStaphylococcus aureus, respectively) as well as excellent hemocompatibility and biocompatibility. Furthermore, the results of applying the Exos to the dGQH20hybrid scaffold showed that the Exo promoted the cell attachment and proliferation on the scaffold, and also showed a significant increase in osteogenesis and vascularity regeneration in the dGQH@Exo scaffoldsin vitroandin vivo. Overall, this novel dECM/Gel/QCS/nHAp hybrid scaffold laden with Exo has a considerable potential application in reservation of craniofacial bone defects.

The phytopathogen Dickeya dadantii 3937 cpxR locus gene participates in the regulation of virulence and the global c-di-GMP network.

Bacteria use signal transduction systems to sense and respond to their external environment. The two-component system CpxA/CpxR senses misfolded envelope protein stress and responds by up-regulating envelope protein factors and down-regulating virulence factors in several animal pathogens. Dickeya dadantii is a phytopathogen equipped with a type III secretion system (T3SS) for manipulating the host immune response. We found that deletion of cpxR enhanced the expression of the T3SS marker gene hrpA in a designated T3SS-inducing minimal medium (MM). In the ∆cpxR mutant, multiple T3SS and c-di-GMP regulators were also up-regulated. Subsequent analysis revealed that deletion of the phosphodiesterase gene egcpB in ∆cpxR abolished the enhanced T3SS expression. This suggested that CpxR suppresses EGcpB levels, causing low T3SS expression in MM. Furthermore, we found that the ∆cpxR mutant displayed low c-di-GMP phenotypes in biofilm formation and swimming. Increased production of cellular c-di-GMP by in trans expression of the diguanylate cyclase gene gcpA was negated in the ∆cpxR mutant. Here, we propose that CpxA/CpxR regulates T3SS expression by manipulating the c-di-GMP network, in turn modifying the multiple physiological activities involved in the response to environmental stresses in D. dadantii.

Effect of modified radical mastectomy combined with neo-adjuvant chemotherapy on postoperative recurrence rate, negative emotion, and life quality of patients with breast cancer.

Breast cancer (BC) is mainly treated by surgery combined with chemotherapy, radiotherapy, and drugs comprehensively in clinical practice, and such a combined treatment can improve the survival rate of patients. This study was designed to determine the effect of modified radical mastectomy (MRM) combined with neo-adjuvant chemotherapy on patients with BC. Clinical data of 80 patients with BC were analyzed retrospectively. The patients were assigned to the control group (n=39) treated with MRM or the therapy group (n=41) treated with additional neo-adjuvant chemotherapy based on MRM. In this study, patients treated with MRM combined with neo-adjuvant chemotherapy experienced significantly shorter operation time and hospitalization time, less bleeding volume, and higher effective treatment rate than the control group. Moreover, the therapy group showed a significantly lower incidence of complications and higher life quality than the control group. Cox regression analysis showed that neo-adjuvant chemotherapy was an independent factor affecting the progression-free survival time of patients. This study has revealed the application value of MRM combined with neo-adjuvant chemotherapy in patients with BC.