Emulation and evaluation of tumor cell combined chemotherapy in isotropic/anisotropic collagen fiber microenvironments.

The rapid emergence of anisotropic collagen fibers in the tissue microenvironment is a critical transition point in late-stage breast cancer. Specifically, the fiber orientation facilitates the likelihood of high-speed tumor cell invasion and metastasis, which pose lethal threats to patients. Thus, based on this transition point, one key issue is how to determine and evaluate efficient combination chemotherapy treatments in late-stage cancer. In this study, we designed a collagen microarray chip containing 241 high-throughput microchambers with embedded metastatic breast cancer cell MDA-MB-231-RFP. By utilizing collagen's unique structure and hydromechanical properties, the chip constructed three-dimensional isotropic and anisotropic collagen fiber structures to emulate the tumor cell microenvironment at early and late stages. We injected different chemotherapeutic drugs into its four channels and obtained composite biochemical concentration profiles. Our results demonstrate that anisotropic collagen fibers promote cell proliferation and migration more than isotropic collagen fibers, suggesting that the geometric arrangement of fibers plays an important role in regulating cell behavior. Moreover, the presence of anisotropic collagen fibers may be a potential factor leading to the poor efficacy of combined chemotherapy in late-stage breast cancer. We investigated the efficacy of various chemotherapy drugs using cell proliferation inhibitors paclitaxel and gemcitabine and tumor cell migration inhibitors 7rh and PP2. To ensure the validity of our findings, we followed a systematic approach that involved testing the inhibitory effects of these drugs. According to our results, the drug combinations' effectiveness could be ordered as follows: paclitaxel + gemcitabine > gemcitabine + 7rh > PP2 + paclitaxel > 7rh + PP2. This study shows that the biomimetic chip system not only facilitates the creation of a realistic in vitro model for examining the cell migration mechanism in late-stage breast cancer but also has the potential to function as an effective tool for future chemotherapy assessment and personalized medicine.

Cellulose-based light-management film exhibiting flame-retardant and thermal-healing properties.

The increased use and expansion of biomass applications offer a viable approach to diminish reliance on petroleum-derived resources and promote carbon neutrality. Cellulose, being the most abundant natural polymer on Earth, has garnered considerable attention. This study introduces a straightforward method to fabricate a cellulose-based multifunctional composite film designed for efficient light management, specifically featuring flame retardant and thermal-healing capabilities. The film incorporates a microfibrillated cellulose (MFC) matrix with functional components, namely benzoxazine resin (BR) and 2-hydroxyethyl methacrylate phosphate (HEMAP). Utilizing dynamic covalent crosslinking, the composite films exhibit satisfactory self-healing properties. The combined effects of BR and HEMAP contribute to the effective flame retardancy of the composite film. Furthermore, the resulting film shields ultraviolet and blue light, offering comfortable interior lighting by mitigating harsh light and extending light propagation. The film also demonstrates favorable water resistance and high tensile strength. The exceptional multifunctional properties, coupled with its safety and extended service life, position it as a potential optical management film for smart building materials.

Research Progress of TCM Therapy for Rotator Cuff Injury.

Rotator cuff injury is a common orthopedic disease with high morbidity, which is one of the most important reasons for shoulder pain and limited movement. With the development of more research, the Traditional Chinese Medicine (TCM) therapy for rotator cuff injury is increasingly rich and has achieved a good curative effect. TCM has certain characteristics and advantages, which may become the main development trend of the treatment. By consulting the relevant literature on TCM therapy for rotator cuff injury in recent years, we found that commonly used TCM therapy include Chinese herbal therapy, Chinese herbal compounds, External treatment of Chinese herbal therapy, Acupuncture therapy, Floating needle therapy，Massage therapy, and others, which make a great clinical effect. This paper summarizes and analyzes the common TCM therapy of the rotator cuff injury, to provide new ideas for the selection of clinical treatment options.

Research Progress in Single-herb Chinese Medicine and Compound Medicine for Knee Osteoarthritis.

Due to an increase in the aging population, osteoarthritis (OA), especially knee osteoarthritis (KOA), has increasingly become one of the diseases affecting the quality of life of the elderly. As the pathogenesis of KOA is still unclear, Western medicine treatment lacks specificity, and surgical treatment is difficult to cover all patients. Therefore, in recent years, traditional Chinese medicine (TCM) for the conservative treatment of KOA has received increasing attention. The advantages of TCM are clear， such as relief of symptoms, fewer adverse reactions, and wider applicability to patients. This paper mainly discusses the research progress in single-herb TCM and TCM compounds for KOA, aiming to demonstrate the effectiveness of TCM in the treatment of KOA. It also provides ideas for future research on the treatment of KOA by TCM and the pathogenesis of knee osteoarthritis.

Guidelines for the Diagnosis and Treatment of Rotator Cuff Tear with Integrated Traditional Chinese and Western Medicine.

Rotator cuff tear is one of the common diseases among middle-aged and elderly people, which has a great impact on patients' physical and mental health and quality of life. The integrative medicine based on traditional Chinese medicine has certain characteristics and advantages in the diagnosis and treatment of Rotator cuff tear. Chinese medicine, which mainly focus on plant-based natural products, has a relatively stable and reliable curative effect. It is of great significance to formulate the combined diagnosis and treatment plan for Rotator cuff tear based on evidence-based medicine, which can help to make the clinical diagnosis and treatment techniques of Chinese and Western medicine more scientific and standardized, and achieve better therapeutic effects. This guideline standardizes the diagnosis and treatment process of Rotator cuff tear from the aspects of range, terminology and definition, diagnosis, TCM syndrome differentiation, treatment, functional exercise, prevention and care, etc. It can better provide clinicians with diagnosis and treatment strategies and suggestions. This guideline adapts well to clinical practice and is both safe and effective.

Research progress on the treatment of knee osteoarthritis combined with osteoporosis by single-herb Chinese medicine and compound.

Knee osteoarthritis (KOA) is a degenerative disease with synovial inflammation, articular surface cartilage degeneration, meniscus degeneration, ligament and muscle changes, subchondral bone changes, and osteophyte formation around the joint as the main pathological changes. Osteoporosis (OP) is a disease characterized by low bone mass and deterioration of the microstructure of bone tissue. KOA and OP are both geriatric diseases, and the incidence of KOA combined with OP is high, but there is a lack of specific drugs, and the major treatments are limited to drug therapy. Most traditional Chinese medicine (TCM) treatments use plant-based natural products, and they help patients obtain good clinical benefits and at the same time provide researchers with ideas to study the mechanism of disease occurrence and the relationship between the two diseases. This article summarizes the research progress of TCM monomers and TCM compounds that are frequently used to treat KOA combined with OP to provide ideas for future clinical treatments and related basic research.

Genomic characteristics and prognosis of lung cancer patients with MSI-H: A cohort study.

BACKGROUND: Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported. METHODS: Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression. RESULTS: Among 12,484 lung cancer patients screened, 66 were found with MSI-H, the proportion was as low as 0.5%. Compared with Microsatellite stability (MSS), TMB was higher in MSI-H lung cancer patients, while PD-L1 expression showed no considerable difference between MSI-H and MSS. After propensity score matching, compared with MSS, the most common companion mutations in MSI-H were TP53, BRCA2, TGFBR2, PTEN and KMT2C. In MSI-H lung adenocarcinoma with EGFR mutation, TGFBR2 and ERBB2 had higher mutation frequency than in MSS. CONCLUSION: The current study reveals the genetic characteristics of MSI-H lung cancer, which advanced our understanding of MSI-H lung cancer.

3D collagen microchamber arrays for combined chemotherapy effect evaluation on cancer cell numbers and migration.

Breast cancer metastasis involves complex mechanisms, particularly when patients are undergoing chemotherapy. In tissues, tumor cells encounter cell-cell interactions, cell-microenvironment interactions, complex nutrient, and drug gradients. Currently, two-dimensional cell culture systems and animal models are challenging to observe and analyze cell responses to microenvironments with various physical and bio-chemical conditions, and microfluidic technology has been systematically developed to address this dilemma. In this study, we have constructed a combined chemotherapy evaluation chip (CCEC) based on microfluidic technology. The chip possesses 192 diamond-shaped microchambers containing MDA-MB-231-RFP cells, and each microchamber is composed of collagen to mimic breast cancer and its surrounding microenvironment. In addition, by adding medium containing different drugs to the medium channels of CCEC, composite drug (paclitaxel+gemcitabine+7rh and paclitaxel+fluorouracil+PP2) concentration gradients, and single drug (paclitaxel, gemcitabine, 7rh, fluorouracil, PP2) concentration gradients have been established in the five collagen regions, respectively, so that each localized microchamber in the regions has a unique drug microenvironment. In this way, we evaluated the composite and single chemotherapy efficacy on the same chip by statistically analyzing their effects on the numbers and migration of the cell. The quantitative results in CCECs reveal that the inhibition effects on the numbers and migration of MDA-MB-231-RFP cell under the composite drug gradients are more optimal than those of the single drugs. Besides, the cancer cell inhibition effect between the groups composed of two drugs has also been compared, that is the paclitaxel+gemcitabine, paclitaxel+fluorouracil, and paclitaxel+PP2 have better cell numbers and migration inhibition effects than paclitaxel+7rh. The results indicate that the bio-mimetic and high-throughput combined chemotherapy evaluation platform can serve as a more efficient and accurate tool for preclinical drug development and screening.

Research progress of plant medicine and Chinese herbal compounds in the treatment of rheumatoid arthritis combined with osteoporosis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. The clinical manifestations of various joint pain and bone destruction are common. RA has a high disability rate and is closely related to local and systemic osteoporosis (OP). RA can occur at any age, however, its incidence increases with age. Most patients are 40 to 50 years old with an incidence among women approximately 3 to 5 times more than among men. Osteoporosis is a kind of metabolic bone disease characterized by bone mass and bone microstructure damage and is one of the common complications of RA. Currently, in the clinic, more patients develop RA with OP symptoms. Therefore, both OP and RA-related factors should be considered in the OP treatment of RA. Currently, there is more and more research on RA combined with OP drugs, including basic drugs, bone resorption inhibitors, bone formation promoters, and anti-rheumatic drugs to improve the condition. The high cost or limited efficacy of certain Western drugs, coupled with their potential for adverse reactions during treatment highlight the pressing need for novel pharmaceuticals in clinical practice. In recent years, traditional Chinese medicine (TCM) can improve the bone formation and bone resorption indexes of patients with RA, regulate the balance of osteoclasts and osteoblasts, and regulate the immune inflammatory response, so as to treat RA combined with OP. This article discusses the advancements in single Chinese medicine and Chinese medicine combination treatments for RA complicated with OP, focusing on the mechanism of action and syndrome differentiation and classification, to offer new ideas for future clinical prevention and treatment.

Comfort Prediction of Office Chair Surface Material Based on the ISSA-LSSVM.

This study serves the purpose of assisting users in selecting a comfortable seat surface material for office chairs and enhancing users' comfort while using office chairs. To address the issue that the selection of traditional seat surface material is too subjective and that the prediction effect is poor, an improved sparrow search algorithm (ISSA) optimized least squares support vector machine (LSSVM) method for office chair seat surface material comfort prediction has been proposed. Sparrow Search Algorithm (SSA) was optimized with Sobol sequences, nonlinear inertial weights, and a crisscross optimization algorithm to produce the Improved Sparrow Search Algorithm (ISSA), and then the relevant parameters of the LSSVM algorithm were optimized with the modified algorithm to improve its prediction performance. The prediction accuracy of the ISSA-LSSVM model is as high as 95.75% by combining the body pressure distribution experiments; the root mean square error (RMSE) is 0.29; the goodness of fit (R2) is 0.92; the mean absolute error (MAE) is 0.24; the standard deviation (RSD) is 5.99%. The ISSA-LSSVM model predicts seat surface material comfort more accurately and reliably. This strategy can assist consumers to narrow down their seat surface material choices and even suggest an optimal selection. In this way, it can boost users' pleasure with office chairs, which has great potential for wide application.

Preparation, Characterization, and Performance Evaluation of Petroleum Asphalt Modified with Bio-Asphalt Containing Furfural Residue and Waste Cooking Oil.

The study aims to analyze the feasibility of proposing waste cooking oil and industrial waste furfural residue as raw materials to prepare bio-asphalt as partial substitutes for petroleum asphalt, so as to reduce the cost of pavement construction and decrease the consumption of non-renewable resources. In this study, 90# petroleum asphalt was partially substituted with the bio-asphalt in different proportions to prepare biomass-modified petroleum asphalt, the performance of which was first evaluated based on three indices: penetration, softening point, and ductility. Comparison of the crystal structures of the bio-asphalt and furfural residue were enabled by X-ray diffraction, and the blending mechanism and microscopic morphologies of the biomass-substituted asphalt mixtures were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. The results showed that the bio-asphalt was hydrophobic and exhibited excellent compatibility with 90# petroleum asphalt. The partial substitution of petroleum asphalt with bio-asphalt improved the low-temperature crack resistance of the asphalt by adversely affecting the high-temperature stability of the asphalt; however, when the bio-asphalt content was 8 wt.%, the performance parameters of the biomass-modified asphalt met the requirements of the 90# petroleum asphalt standard.

Biological gel-based microchamber array for tumor cell proliferation and migration studies in well-controlled biochemical gradients.

Breast cancer metastasis is a complex process controlled by multiple factors, including various cell-cell interactions, cell-environment coupling, and oxygen, nutrient and drug gradients that are intimately related to the heterogeneous breast tissue structure. In this study, we constructed a high-throughput in vitro biochip system containing an array of 642 microchambers arranged in a checkerboard configuration, with each chamber embedded in a composite extracellular matrix (ECM) composed of engineered collagen and Matrigel to mimic local heterogeneous environment in vivo. In addition, a controllable complex tetragonal chemical concentration profile can be achieved by imposing chemical compounds at the four boundaries of the chip, leading to distinct local nutrient and/or drug gradients in the individual microchambers. Here, the microchamber array with composite ECM (MACECM) device aims to simulate multiple tumor cell niches composed of both breast epithelial cells (MCF-10A-GFP) and metastatic breast cancer cells (MDA-MB-231-RFP), which enables systematic studies of cell responses to a variety of biochemical conditions. The results obtained from the MACECM studies indicate that discoidin domain receptor 1 (DDR1) inhibitor 7rh and matrix metalloproteinase inhibitor batimastat, in association with epidermal growth factor (EGF) had no significant effects on the growth of MCF-10A-GFP cells, but had significant effects on DDR1 expression and the related migratory behavior of MDA-MB-231-RFP cells. The MACECM design not only enables the construction of a more realistic in vitro model for investigating cancer cell migration mechanisms but also has considerable potential for further development as a platform for next-generation high-throughput and therapeutic screening (e.g., anti-cancer drug evaluation) and personalized medicine.

Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle.

PURPOSE: Tumor metastasis and drug resistance have always been vital aspects to cancer mortality and prognosis. To compromise metastasis and drug resistance, a nanoparticle IPPD-PHF2 (IR780/PLGA-PEI(Dox)-PHF2) has been engineered to accomplish efficient targeted epigenotherapy forced by PHF2-induced MET (mesenchymal to epithelial transition). MATERIALS AND METHODS: IPPD-PHF2 nanoparticle was synthesized and characterized by several analytical techniques. The transfection efficiency of IPP-PHF2 (IR780/PLGA-PEI-PHF2) was compared with PP-PHF2 (PLGA-PEI-PHF2) in vitro by WB and in vivo by IHC, and the cytotoxicity of IPP was compared with Lipo2000 in vitro by CCK8 assay. The inhibition of cancer cell migration caused by PHF2-upregulation was tested by wound healing assay, and the enhanced chemotherapeutic sensitivity was detected by flow cytometry. Tumor-targeting property of IPPD-PHF2 was proved by fluorescent imaging in vivo with MDA-MB-231 tumor-bearing nude mice. Except for fluorescent imaging ability, considerable photoacoustic signals of IPPD-PHF2 at tumor sites were verified. The anti-tumor activity of IPPD-PHF2 was investigated using in vivo human breast cancer MDA-MB-231 cell models. RESULTS: Tumor-targeting nanoparticle IPPD-PHF2 had an average size of about 319.2 nm, a stable zeta potential at about 38 mV. The encapsulation efficiency of doxorubicin was around 39.28%, and the adsorption capacity of plasmids was about 64.804 µg/mg. Significant up-regulation of PHF2 induced MET and caused reduced migration as well as enhanced chemotherapeutic sensitivity. Either IPPD (IR780/PLGA-PEI(Dox)) or IPP-PHF2 (IR780/PLGA-PEI-PHF2) presented minor therapeutic effects, whereas IPPD-PHF2 specifically accumulated within tumors, showed extraordinary transfection efficiency specifically in tumor sites, acted as inhibitors of metastasis and proliferation, and presented good multimodality imaging potentials in vivo. CONCLUSION: IPPD-PHF2 NPs is a promising tool to bring epigenotherapy into a more practical era, and the potential application of harm-free multimodality imaging guidance is of great value.

Efficacy and safety of bevacizumab-based maintenance therapy in metastatic colorectal cancer: A meta-analysis.

OBJECTIVE: To identify the optimal treatment strategy after first-line induction chemotherapy for metastatic colorectal cancer (mCRC). METHODS: We conducted a meta-analysis of randomized controlled trials comparing bevacizumab-based maintenance therapy, observation, and continuous chemotherapy.We searched the PubMed, Embase, and Cochrane databases for relevant articles published through March 2018. All randomized phase-III trials evaluating bevacizumab-based maintenance treatment after bevacizumab-based induction treatment were eligible for inclusion. The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. Hazard ratios (HRs) with 95% confidence intervals (CIs) or data for calculating HRs with 95% CIs were extracted. The RevMan v5.3 (Copenhagen, Denmark) software was used for data analysis. RESULTS: Nine trials (3121 patients) were included in this meta-analysis. Compared with observation alone, bevacizumab-based maintenance therapy significantly improved PFS (HR: 0.62, 95% CI: 0.47-0.82) and showed a trend toward prolonged OS (HR: 0.93, 95% CI: 0.83-1.05). The incidence of grade 3/4 toxicity, including hypertension and fatigue, was higher after maintenance therapy than after observation alone. PFS (HR: 0.91, 95% CI: 0.70-1.18) and OS (HR: 0.88, 95% CI: 0.74-1.04) did not differ between the maintenance treatment and continuous chemotherapy groups. Grade 3/4 toxicity, including diarrhea and sensory neuropathy, was less common after maintenance therapy than after continuous chemotherapy. CONCLUSION: Bevacizumab-based maintenance therapy significantly improved PFS, showed a trend toward prolonged OS, and reduced cumulative grade 3/4 toxicity relative to continuous chemotherapy with comparable efficacy. Although maintenance therapy was beneficial, the optimal strategy should be individualized.

Traditional Chinese Medicine Prolongs Progression-Free Survival and Enhances Therapeutic Effects in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)Treated Non-Small-Cell Lung Cancer (NSCLC) Patients Harboring EGFR Mutations.

BACKGROUND Lung cancer is the most common cause of cancer-associated deaths worldwide. This study aimed to investigate the efficacy and safety of Traditional Chinese Medicine combining EGFR-TKIs in treatment of NSCLC patients harboring EGFR mutations. MATERIAL AND METHODS This study involved 153 advanced-stage NSCLC patients harboring EGFR mutations. Patients were divided into a Control group (administered EGFR-TKI, n=61) and an Experimental group (administered Traditional Chinese Medicine combining EGFR and TKI, n=92). Progression-free survival (PFS) was evaluated for exon 19 deletion and/or 21 deletion patients. Disease control rate (DCR) was assessed to observe therapeutic effects. Adverse effects, including rashes, diarrhea, ALT/AST increase, dental ulcers, and onychia lateralis, were also evaluated. RESULTS TCM combining EGFR-TKI (90.11%) demonstrated no DCR improvement compared to single EGFR-TKI (83.33%) (p>0.05). Median PFS (mPFS) of TCM combining EGFR-TKI (13 months) was significantly longer compared to that in the single EGFR-TKI group (8.8 months) (p=0.001). For 19DEL mutant NSCLC, the mPFS (11 months) in TCM combining EGFR-TKI was significantly longer compared to single EGFR-TKI (8.5 months) (p=0.007). The mPFS of L858 mutant NSCLC patients in EGFR-TKI combining CTM (14 months) was significantly longer compared to single EGFR-TKI (9.5 months) (p=0.015). TCM combining EGFR-TKI was more inclined to prolong mPFS of NSCLC with exon 21 deletion. TCM combining EGFR-TKI illustrated no additional adverse effects in NSCLC patients (p=0.956). CONCLUSIONS Application of Traditional Chinese Medicine prolonged progression-free survival and enhanced therapeutic effect in NSCLC patients harboring EGFR mutations receiving EGFR-TKI treatment. Meanwhile, adjunctive Chinese medicine combining EGFR-TKI in NSCLC with EGFR mutations caused no adverse effects.

Prognostic significance of NANOG expression in solid tumors: a meta-analysis.

PURPOSE: NANOG is a tumor marker and indicates poor prognosis in various neoplasms; however, the evidence is controversial. This meta-analysis investigated the association of NANOG expression and clinicopathological features, and it impact on survival of patients with malignant tumors. METHODS: Studies published through May 31, 2018 were retrieved from PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure. Two researchers independently screened the content and quality of studies and extracted data. Correlations of NANOG expression, clinicopathological variables, and survival were analyzed and the combined odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: Thirty-three articles including 35 data sets of 3,959 patients were analyzed. Overall, elevated NANOG expression was associated with poor overall survival (HR = 2.19; 95% CI: 1.87-2.58, P<0.001) and poor disease-free survival (HR = 2.21, 95% CI: 1.54-3.18, P<0.001). Subgroup analysis found that NANOG expression was associated with worse overall survival in non-small cell lung (HR = 1.87; 95% CI: 1.26-2.76, P = 0.002), head and neck (HR = 2.29; 95% CI: 1.75-3.02, P<0.001), and digestive system (HR = 2.38; 95% CI: 1.95-2.91, P<0.001) cancers. Moreover, we found that high NANOG expression was associated with poor tumor differentiation (OR = 2.63; 95% CI: 1.59-4.55, P = 0.001), lymph node metastasis (OR = 2.59; 95% CI: 1.50-4.47, P = 0.001), advanced TNM stage (OR = 2.22; 95% CI: 1.42-3.45, P<0.001), and T stage (OR = 0.44; 95% CI: 0.20-0.93, P = 0.031). CONCLUSION: The evidence supports NANOG as a tumor biomarker to guide clinical management and indicate prognosis. Additional studies are needed to further validate these results.

3,3'-Diindolylmethane suppresses ovarian cancer cell viability and metastasis and enhances chemotherapy sensitivity via STAT3 and Akt signaling in vitro and in vivo.

Signal transducer and activator of transcription-3 (STAT3) protein is constitutively activated in ovarian cancer. The purpose of this study was to investigate the effects of 3,3'-diindolylmethane (DIM) on the regulation of STAT3 signaling and ovarian cancer cell viability, invasion, and sensitivity to chemotherapy. Ovarian cancer SKOV3 and A2780 cell lines were treated with various concentrations of DIM for different periods of time for assessment of cell viability as well as gene expression before and after knockdown of STAT3 expression using STAT3 shRNA. DIM treatment potently suppressed the viabilities of ovarian cancer cells. Consequently, DIM inhibited xenograft growth in nude mice. In addition, at the gene level, DIM inhibited phosphorylation of STAT3 and AKT proteins and expression of their downstream proteins. Moreover, knockdown of STAT3 expression significantly enhanced DIM antitumor activity and cisplatin sensitivity. Their combination suppressed the protein expression of survivin, Bcl-2, Mcl-1, HIF-1α, VEGF, and MMPs, but activated caspase-3. Taken together, the antitumor activity of DIM is via inhibition of the STAT3 and Akt signaling pathways. The combination of STAT3 knockdown with DIM treatment could be further evaluated as a therapeutic strategy for the treatment of advanced ovarian cancer.

[Role and mechanism of FOXG1 in invasion and metastasis of colorectal cancer].

This study was aimed to investigate the effect of Forkhead Box G1 (FOXG1) on the epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells and the underlying mechanism. For this purpose, FOXG1 lentiviral interference (shRNA) plasmid and expression plasmid were constructed. Western blotting was used to analyze the expression of FOXG1 protein in five CRC cells, namely RKO, SW480, SW620, LoVo and DLD-1. The shRNA fragment of FOXG1 (shFOXG1) was designed and synthesized. Recombinant plasmids were obtained with the aid of DNA recombination technique. Double digestion and sequencing were used to identify the recombinant plasmids, and then lentivirus packaging, purification and stable transfection were carried out. Additionally, stable CRC cell lines were screened out. The changes of FOXG1 knockdown and overexpression efficiency, E-cadherin, Vimentin, Fibronectin, Snail, Twist mRNA and protein were investigated respectively by Western blotting and qRT-PCR analysis. Furthermore, the changes of cell morphology after knockdown and cell migration ability were evaluated respectively with optical microscopy, scratch test and Transwell assay. FOXG1 had the highest protein expression in RKO and the lowest in DLD-1 among the five CRC cells. Compared with those of the control group, the cell morphology in FOXG1 knockdown RKO group was changed from spindle into round or polygonal shape, cell polarization was enhanced and tight junction assembly was acclerated while cell migration distance was noticeably decreased. Moreover, the number of cells invaded and migrated through chambers was significantly reduced. Among these key factors of EMT, the expression of E-cadherin was increased while the expressions of Vimentin, Fibronectin, Snail and Twist were decreased. The opposite was the case in the overexpressed FOXG1 group. The overexpression of FOXG1 in CRC promoted the invasion and metastasis of CRC cells and played a crucial role in regulating the EMT. Thus, FOXG1 might be a novel therapeutic target in CRC treatment.

Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1.

Synthetic antidepressants in current use for the complex etiopathogeneses of depression have slow response and remission as well as various unpleasant side effects. As a result, it is imperative to develop new antidepressants with more effectiveness and less severe side effects. Recent studies demonstrated that genipin, the aglycon of geniposide, extracted from Gardenia jasminoides Ellis has antidepressive effects. However, knowledge regarding the molecular mechanisms of its antidepressant effects remains limited. Employing a depression-like mouse model, we confirmed that genipin is capable of correcting depressions-like behaviors induced by prenatal stress in offspring from prenatally stressed dams (defined as PRS mice). In further experiments, we found that the effect of genipin on PRS mice occurs through DNA demethylation by inhibiting DNA methyltransferase 1 (DNMT1), normalizing the expression of reduced brain-derived neurotrophic factor (BDNF) in the hippocampus.

The association between diabetes/hyperglycemia and the prognosis of cervical cancer patients: A systematic review and meta-analysis.

BACKGROUND: The predictive roles of diabetes in the prognosis of many types of cancer have been well studied, but its role in predicting the prognosis of cervical cancer is still controversial. The aim of the study is to evaluate the association between diabetes/hyperglycemia and the prognosis of cervical cancer. METHODS: We conducted a systematic review for peer-reviewed studies indexed in PubMed, Embase, Web of Science, and Wanfang published before December 2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled in the meta-analysis. RESULTS: This systematic review identified 13 studies with a total of 11,091 cervical cancer patients, of which 11 studies were included in the meta-analysis. The study indicated that diabetes was related to poorer overall survival (HR = 1.59, 95% CI: 1.35-1.87, P < .001) and poorer recurrence-free survival (HR = 1.98, 95% CI: 1.47-2.66, P < .001) in cervical cancer patients. The meta-analysis of adjusted HRs also indicated that diabetes was independently associated with poor overall survival (HR = 1.69, 95% CI: 1.38-2.05, P < .001) and poor recurrence-free survival (HR = 1.98, 95% CI: 1.47-2.66, P < .001) in cervical cancer patients. Sensitivity analysis and subgroup analyses showed similar results. No significant heterogeneity was observed for the included studies. CONCLUSIONS: The meta-analysis suggests that diabetes is an important predictive factor for cervical cancer prognosis, and it is linked to poorer survival of cervical cancer patients. Diabetes can serve as a useful index in the prognostic evaluation for patients with cervical cancer.