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Purpose To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia (ATD) using optical coherence tomography angiography (OCTA), to record flash electroretinograms using the RETeval system and to explore changes in retinal function.Methods Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled. All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area, including the vascular length density, the vascular width density and the area of foveal avascular zone (FAZ), as well as the choroidal thickness. The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters. We also recorded the flash electroretinograms (ERG) using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.Results The vessel parameters and average choroid thickness in the macular area of the ATD group was less than the control group, The FAZ area was statistically significantly enlarged in the ATD group. These parameters were correlated with the Mini-Mental State Examination (MMSE) score and the Montreal Cognitive Assessment (MoCA).Conclusions Patients with Alzheimer’s type dementia exhibit decreases in the parameters associated with fundus. In addition, these indicators significantly correlated with the MMSE score and the MoCA score. OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.

Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery. However, transplanted stem cells show a high death percentage, creating challenges to successful transplantation and prognosis. Thus, it is necessary to investigate the mechanisms underlying stem cell death, such as apoptotic cascade activation, excessive autophagy, inflammatory response, reactive oxygen species, excitotoxicity, and ischemia/hypoxia. Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success. Notably, a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate, highlighting the challenges in exploring mechanisms and therapeutic targets. In this review, we focus on programmed cell death in transplanted stem cells. We also discuss some promising strategies and challenges in promoting survival for further study.

Ethnopharmacological relevance Isatidis Radix, the sun-dried roots of Isatis indigotica Fortune ex Lindl., is one of the most usually used traditional Chinese medicines. For centuries, the herb has been employed in clinical practice for treatment of virus infection and inflammation. However, its active ingredients remain unclear. Aim of the study In the present study, the anti-influenza virus activity of epiprogoitrin, progoitrin, epigoitrin and goitrin, the Isatidis Radix derived glucosinolate isomers and their breakdown products, was firstly evaluated in vitro and in ovo and their mechanism of action was investigated. Materials and methods Epiprogoitrin, progoitrin, epigoitrin and goitrin were isolated from Isatidis Radix by chiral separation. In vitro and in ovo evaluations were performed on Madin-Darby canine kidney (MDCK) cells and embryonated eggs respectively, both using protocols including prevention, treatment and virus neutralization. Hemagglutination (HA) and neuraminidase (NA) inhibition assays were performed for further understanding of the antiviral mechanism. Results Isatidis Radix derived glucosinolate isomers and their breakdown products all exhibited dose-dependent inhibition effect against influenza A virus (H1N1) without toxicity. The antiviral potency of the components was in the order of progoitrin > goitrin > epigoitrin > epiprogoitrin. The attachment of the constituents to the viral envelope conduced to the mechanism of their antiviral action without disturbing viral adsorption or budding. Conclusion Taken together, these results are promising for further development of Isatidis Radix and may contribute an adjunct to pharmacotherapy for influenza virus infection., Graphical abstract Image 1

A strategy developed for obtaining positive cellular responses remains to be focused in the filed of functional biomimetics. In this study, a hydrogel covered simvastatin-loaded polyetheretherketone (PEEK) bio-composites was constructed with the purpose of bone tissue regeneration therapy. Briefly, a three-dimensional (3D) porous structure was fabricated on PEEK surface; then the substrate was functionalized with the poly(L-lactic acid)/simvastatin porous film and hyaluronic acid hydrogel subsequently. In vitro cell attachment, proliferation, and cytoskeletal observation experiments reveal that our scaffolds show better bio-affinity due to the layer of hyaluronic acid hydrogel compared with control. Furthermore, the alkaline phosphatase activity, calcium mineral deposition evaluation, and gene expression for osteogenic potential all exhibit that the superior osteogenic differentiation of MC3T3-E1 pre-osteoblasts on our scaffolds. Therefore, our PEEK samples loaded with simvastatin and covered with hyaluronic acid hydrogel hold great potential in clinical applications for bone repair.

Breast cancer is a prevalent malignant cancer worldwide, and a lack of defined biomarkers for early prognostication contributes to its high associated mortality rate, especially in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. In the present study, HER-2 mRNA levels in patients were detected prior to surgery and during neoadjuvant chemotherapy to explore its potential diagnostic and prognostic value. Blood samples were collected from 70 patients with breast cancer, including 50 HER-2-negative and 20 HER-2-positive patients, prior to and following surgery (postoperative, n=13; neoadjuvant chemotherapy, n=5); the control group included 35 samples from healthy individuals. The relative mRNA level of HER-2 in blood was determined by one-step reverse transcription-quantitative polymerase chain reaction. HER-2 expression curves of measurements taken during neoadjuvant chemotherapy were compared with the tumor size. A significant difference in the blood HER-2 mRNA level was observed between healthy women and patients with breast cancer (P

Background Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4. Methods Western blot, Real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) were used to detect the expression of LAMA4 in TNBC. The effects of LAMA4 on TNBC cell proliferation, migration and invasion were also explored in vitro. The potential miRNA that targets LAMA4 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis. Results Our study showed LAMA4 mRNA (p = 0.001) and protein (p = 0.005) expression in TNBC tissue samples were elevated compared with adjacent normal tissue samples, and LAMA4 was mainly expressed in the cytoplasm of breast carcinoma cells. Knockdown of LAMA4 inhibited TNBC cell proliferation, migration and invasion in vitro. Moreover, further study revealed that LAMA4 was a putative target of miR-539, and miR-539 negatively regulated LAMA4 expression by directly targeting its 3′-UTR. Conclusions Our study suggested that miR-539 suppressed the expression of LAMA4. LAMA4 plays an important role in tumor progression and may be an important target in treatment of TNBC.

Golgi phosphoprotein 3 (GOLPH3) has recently been implicated as an oncogene involved in the development of carcinoma in a number of organs. The expression of GOLPH3 in prostate cancer (PCa) tissues was investigated in the present study. Human PC-3 and LNCaP PCa cell lines were analyzed in order to assess whether silencing of GOLPH3 expression affects cell vitality, migration and invasion, in vitro. An immunohistochemistry analysis was performed in order to measure the expression of GOLPH3 in samples from 117 patients with PCa and from 50 patients with benign prostatic hyperplasia (BPH). Associations between GOLPH3 expression and clinicopathological parameters, such as overall survival, were assessed. GOLPH3 expression was shown to be significantly greater in PCa tissues than in BPH tissues. GOLPH3 expression was positively correlated with Gleason score (P=0.031), tumor stage (T stage; P=0.020) and lymph node status (P=0.013), in patients with PCa. Biochemical recurrence-free survival (serum prostate-specific antigen-based) and overall survival, were reduced in patients with GOLPH3-positive PCa. A multivariate analysis indicated that GOLPH3 expression was an independent predictor of biochemical recurrence-free survival [hazard ratio (HR), 2.943; 95% confidence interval (CI), 1.190-5.521; P=0.028], and of overall survival (HR, 4.371; 95% CI, 2.045-7.109; P=0.014). Transfection with GOLPH3‑targeted small interfering RNA reduced the capability of PC-3 and LNCaP cell lines to proliferate, migrate and invade in vitro, compared with the controls. The level of GOLPH3 expression in radical prostatectomy samples may be useful for predicting biochemical recurrence-free survival and overall survival in patients with PCa.

Background Expression of the polymeric immunoglobulin receptor (pIgR), a transporter of polymeric IgA and IgM, is commonly increased in response to viral or bacterial infections, linking innate and adaptive immunity. Abnormal expression of pIgR in cancer was also observed, but its clinical relevance remains uncertain. Methods A human hepatocellular carcinoma (HCC) tissue microarray (n = 254) was used to investigate the association between pIgR expression and early recurrence. An experimental lung metastasis model using severe combined immune-deficient mice was applied to determine the metastatic potential of Madin–Darby canine kidney (n = 5 mice per group) and SMMC-7721 (n = 12 mice per group) cells overexpressing pIgR vs control cells. RNA interference, immunoprecipitation, and immunoblotting were performed to investigate the potential role for pIgR in the induction of epithelial–mesenchymal transition (EMT). In vitro studies (co-immunoprecipitation, immunoblotting, and migration, invasion, and adhesion assays) were used to determine the mechanisms behind pIgR-mediated metastasis. All statistical tests were two-sided. Results High expression of pIgR was statistically significantly associated with early recurrence in early-stage HCC and in hepatitis B surface antigen–positive HCC patients (log-rank P = .02). Mice injected with pIgR-overexpressing cells had a statistically significantly higher number of lung metastases compared with respective control cells (Madin–Darby canine kidney cells: pIgR mean = 29.4 metastatic nodules per lung vs control mean = 0.0 metastatic nodules per lung, difference = 29.4 metastatic nodules per lung, 95% confidence interval = 13.0 to 45.8, P = .001; SMMC-7721 cells: pIgR mean = 10.4 metastatic nodules per lung vs control mean = 2.2 metastatic nodules per lung, difference = 8.2 metastatic nodules per lung, 95% confidence interval = 1.0 to 15.5, P = .03). Furthermore, high expression of pIgR was sufficient to induce EMT through activation of Smad signaling. Conclusions pIgR plays a role in the induction of EMT. Our results identify pIgR as a potential link between hepatitis B virus– derived hepatitis and HCC metastasis and provide evidence in support of pIgR as a prognostic biomarker for HCC and a potential therapeutic target. J Natl Cancer Inst 2011;103:1696–1712

To investigate the pharmacokinetics of imatinib in Chinese chronic myelogenous leukemia (CML) patients.Fourty-six naïve Chinese CML patients treated with imatinib (400 and 600 mg daily, n=36 and 10, respectively) were recruited. The correlations of imatinib (400 mg) trough plasma concentrations (C(mins)) with the patients' characteristics and responses were analyzed.The overall mean (+/-SD, CV%) steady-state C(mins) for imatinib at 400 mg (n=36) and 600 mg (n=10) daily was 1325.61 ng/mL (+/-583.53 ng/mL; 44%) and 1550.90 ng/mL (+/-462.63 ng/mL; 30%), respectively, and no statistically significant differences were found between them (P=0.267). At 400 mg daily, female patients had significantly higher C(mins) than the male patients (P=0.048), and molecular responses were not correlated with imatinib C(mins), but they were correlated with time elapsed before imatinib therapy.The results suggest that Chinese CML patients have higher imatinib C(mins) than their Caucasian counterparts and that the optimal initial imatinib dose for them requires further investigation.