PReD-Bench/PRed-Bench huggingface dataset:
Formulation and evaluation of chitosan-chondroitin sulphate based nasal inserts for zolmitriptan
Authors: Gurpreet Kaur
Kirandeep Kaur
Journal: BioMed Research International (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Bioadhesive nasal dosage forms; chondroitin sulphate; chitosan; zolmitriptan; interpolymer complexes
Affiliations: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India., Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India

Abstract:  Bioadhesive nasal dosage forms are an attractive method for overcoming rapid mucociliary clearance transport in the nose and for delivering the drug directly to brain. The present study was designed to formulate chondroitin sulphate (CS) and chitosan (CH) nasal inserts employing zolmitriptan, an antimigraine drug. The interpolymer complexes (IPC) formed between -COO(-) and -OSO3(-) groups of CS and -NH3(+) group of CH were characterized by infrared spectroscopy (IR), differential scanning analysis (DSC), and zeta potential studies. The unloaded and loaded nasal inserts were evaluated for water uptake studies, and bioadhesive strength studies, scanning electron microscopic studies (SEM). The in vitro drug release and in situ permeation studies were carried out on loaded nasal inserts. The DSC and IR studies confirmed the formation of a complex between the two polymers. The results indicated that the formulation F1 (CH : CS; 30 : 70) was demonstrating the highest bioadhesive strength and zeta potential. The presence of porous structure in the nasal inserts was confirmed by the SEM analysis. Further, in vitro and in situ release studies demonstrated that formulations F9 and F11 (drug : polymer; 1 : 10) were releasing 90% and 98% zolmitriptan over a period of 8 h. It can be concluded that nasal inserts formulated from chitosan-chondroitin sulphate (CH-CS) interpolymer complex (IPC) can be used for delivery of antimigraine drug to brain. 

Retracted: No

PubPeer comments:
 Fig. 2B:  Protein expression of u03b2-catenin, Wnt3a, GSK-3u03b2 and Axin between the BMSCs group and BMSCs + TNF-u03b1 group ; Fig. 3B:  protein expression of u03b2-catenin, Wnt3a, GSK-3u03b2 and Axin in each group . ![file] The protein blobs here all seem to be drawing on the same limited gamut as those in a distinct oeuvre of studies, as in the following montage. ![] ,
CircRNA 010567 improves myocardial infarction rats through inhibiting TGF-β1
Authors: M Bai
G-X Jiang
C-L Pan
Y-M Zhang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: circRNA 010567; myocardial infarction; myocardial fibrosis; rats; transforming growth factor-β1
Affiliations: Heart Center, the First Affiliated Hospital of Lanzhou University, Lanzhou, China. .

Abstract:  Objective: To observe the intervention effect of circular ribonucleic acid (circRNA) 010567 on myocardial infarction (MI)-induced myocardial fibrosis (MF) in rats, and to explore whether its mechanism of action is related to the regulation on the transforming growth factor-β1 (TGF-β1) signaling pathway. Materials and methods: The rat model of acute MI was established using ligation of the left anterior descending coronary artery. Model rats were randomly divided into circRNA 010567 siRNA group and Model group, with sham operation group as Control group. The effects of circRNA 010567 on the cardiac function, MF, myocardial apoptosis, mRNA, and protein expression levels of TGF-β1 and Smad3 in heart tissues of MI rats were detected using the small animal ultrasound system, Masson staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting, respectively. Results: Compared with Control group, Model group had significantly decreased cardiac function, significantly lower left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS), markedly increased left ventricular end-diastolic diameter (LVDd), and left ventricular end-systolic diameter (LVDs), severe MF, as well as a significantly higher apoptosis rate of myocardial cells, and evidently increased mRNA and protein levels of TGF-β1 and Smad3 in heart tissues. Compared with Model group, circRNA 010567 siRNA group had evidently improved cardiac function, significantly higher LVEF and LVFS, markedly decreased LVDd and LVDs, alleviated MF, a significantly lower apoptosis rate of myocardial cells, and evidently decreased mRNA and protein levels of TGF-β1 and Smad3 in heart tissues. Conclusions: CircRNA 010567 siRNA can improve the cardiac function, alleviate the MF, and inhibit the myocardial apoptosis, thereby further suppressing MI-induced MF, whose mechanism may be related to the inhibition on the TGF-β1 signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 2A.  Myocardial apoptosis in each group. A, TUNEL staining . ![file] Please compare with Figure 3A from [Zhang et al (2019)] .  Cell apoptosis in rat heart tissues evaluated via TUNEL assay. A, TUNEL staining results . ![file] ,
TXNIP mediates high glucose-induced mitophagic flux and lysosome enlargement in human retinal pigment epithelial cells
Authors: Thangal Yumnamcha
Lalit P Singh
Mallika Somayajulu
Takhellambam S Devi
Fayi Yao
Renu A Kowluru
Journal: Biology Open (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hyperglycemia; Lysosome destabilization; Mitophagy; Retinal pigment epithelium; TXNIP.
Affiliations: Department of Ophthalmology, Visual and Anatomical Sciences (OVAS), Wayne State University School of Medicine, Detroit, MI 48201, USA., Department of Ophthalmology, Visual and Anatomical Sciences (OVAS), Wayne State University School of Medicine, Detroit, MI 48201, USA .

Abstract:  Thioredoxin-interacting protein (TXNIP) plays a critical role in oxidative stress, inflammation, apoptosis and the pathogenesis of diabetic retinopathy (DR). However, the role of TXNIP in high glucose-induced retinal pigment epithelium (RPE) dysfunction is still unknown. Here, we show that high glucose (HG; 25 mM,) significantly increases TXNIP expression at both the mRNA and protein levels when compared to low glucose (LG; 5.5 mM) in a human RPE cell line (ARPE-19) and primary human RPE (HRPE) cells. TXNIP upregulation is associated with mitochondrial membrane depolarization, fragmentation and mitophagic flux to lysosomes. We used confocal live-cell imaging of RPE cells expressing mt-Keima, a coral protein that emits green light in mitochondria (alkaline or neutral pH) and red light in the acidic lysosome, to measure mitophagic flux. We observed an elongated mitochondrial network of green mt-Keima under LG, which is fragmented in HG. Red mt-Keima accumulates in lysosomes as small punctate aggregations under LG in both ARPE-19 and HRPE cells, whereas they are significantly enlarged (two- to threefold) under HG. Lysosomal enlargement under HG is further illustrated by lysosomal membrane protein LAMP1-mCherry expression in both ARPE-19 and HRPE cells. Furthermore, HG causes lysosomal cathepsin L inactivation and pro-inflammatory caspase-1 activation in ARPE-19 cells. TXNIP knockdown by shRNA prevents mitochondrial fragmentation, mitophagic flux and lysosome enlargement under HG. In addition, antioxidant N-acetylcysteine (NAC) and Amlexanox (Amlx), an inhibitor of protein kinase TBK1 and of the mitophagic adaptors Optineurin (Optn) and Sequestosome 1 (p62/SQSTM1), prevent mitophagic flux and lysosome enlargement. These results suggest that TXNIP mediates several deleterious effects of high glucose on RPE, which may be implicated in the development of DR. 

Retracted: No

PubPeer comments:
 Two images in Figure 7 appear to overlap (yellow boxes). *** ![file] ,
Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics
Authors: Robert Pascal
John D Sutherland
Addy Pross
Journal: Open Biology (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: abiogenesis; dynamic kinetic stability; irreversibility; metabolism; origin of life
Affiliations: Institut des Biomolécules Max Mousseron UMR5247, CNRS-Universités Montpellier 1 and Montpellier 2, CC17006, Place E. Bataillon, 34095 Montpellier, France., Department of Chemistry, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel, Laboratory of Molecular Biology, MRC, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK

Abstract:  A sudden transition in a system from an inanimate state to the living state-defined on the basis of present day living organisms-would constitute a highly unlikely event hardly predictable from physical laws. From this uncontroversial idea, a self-consistent representation of the origin of life process is built up, which is based on the possibility of a series of intermediate stages. This approach requires a particular kind of stability for these stages-dynamic kinetic stability (DKS)-which is not usually observed in regular chemistry, and which is reflected in the persistence of entities capable of self-reproduction. The necessary connection of this kinetic behaviour with far-from-equilibrium thermodynamic conditions is emphasized and this leads to an evolutionary view for the origin of life in which multiplying entities must be associated with the dissipation of free energy. Any kind of entity involved in this process has to pay the energetic cost of irreversibility, but, by doing so, the contingent emergence of new functions is made feasible. The consequences of these views on the studies of processes by which life can emerge are inferred. 

Retracted: No

PubPeer comments:
 Misleading title: No theory. No science, semantics. Not connected to science of kinetics or thermodynamics out of equilibrium. Improvements: Read state-of-the art on theory + experiment, e.g. https: journals.aps.org prx abstract 10.1103 PhysRevX.7.021051 + references therein Introduce new concepts where necessary and scientific. Use appropriate scientific results and concepts to obtain results. Use same method to check claimed results, omit falsehoods. Credit theoretical+experimental proof for results that are not novel, if proven. Repeat, for other instances ,
Angiogenin protects motoneurons against hypoxic injury
Authors: J Sebastià
D Kieran
M A King
C T Taylor
S F Fitzpatrick
D Joyce
J H M Prehn
B Breen
D F Netteland
Journal: Cell death and differentiation (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cells; hypoxia; hypoxia-inducible factor-1 (HIF-1); hypoxia-responsive genes; motoneurons
Affiliations: Department of Physiology and Medical Physics and RCSI Neuroscience Research Centre, Royal College of Surgeons in Ireland, Dublin, Dublin 2, Ireland.

Abstract:  Cells can adapt to hypoxia through the activation of hypoxia-inducible factor-1 (HIF-1), which in turn regulates the expression of hypoxia-responsive genes. Defects in hypoxic signaling have been suggested to underlie the degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). We have recently identified mutations in the hypoxia-responsive gene, angiogenin (ANG), in ALS patients, and have shown that ANG is constitutively expressed in motoneurons. Here, we show that HIF-1alpha is sufficient and required to activate ANG in cultured motoneurons exposed to hypoxia, although ANG expression does not change in a transgenic ALS mouse model or in sporadic ALS patients. Administration of recombinant ANG or expression of wild-type ANG protected motoneurons against hypoxic injury, whereas gene silencing of ang1 significantly increased hypoxia-induced cell death. The previously reported ALS-associated ANG mutations (Q12L, K17I, R31K, C39W, K40I, I46V) all showed a reduced neuroprotective activity against hypoxic injury. Our data show that ANG plays an important role in endogenous protective pathways of motoneurons exposed to hypoxia, and suggest that loss of function rather than loss of expression of ANG is associated with ALS. 

Retracted: No

PubPeer comments:
 Figure 6D. Much more similar than you would expect. https: imgur.com WVp1jZE ,
Epithelial-mesenchymal transition in oral squamous cell carcinoma triggered by transforming growth factor-beta1 is Snail family-dependent and correlates with matrix metalloproteinase-2 and -9 expressions
Authors: Newell W Johnson
Bin Qiao
Jin Gao
Journal: International Journal of Oncology (2010)
Discipline: CLINICAL MEDICINE
Keywords: Snail; Slug; cancer progression; epithelial-mesenchymal transition (EMT); oral squamous cell carcinoma (OSCC)
Affiliations: Griffith Institute for Health and Medical Research, and School of Dentistry and Oral Health, Gold Coast Campus, Griffith University, QLD 4222, Australia.

Abstract:  Snail and Slug play important roles in cancer progression by promoting epithelial-mesenchymal transition (EMT). Although Snail is well studied, its role in oral squamous cell carcinoma (OSCC) and its regulatory relationship with Slug remain unclear. We aimed to determine whether Snail and Slug interplay occurs in transforming growth factor-beta1 (TGF-beta1)-initiated EMT of OSCC cells, and to assess the expression of matrix metalloproteinases (MMPs) in this process. Three OSCC cell lines, SCC9, SCC15 and SCC25 were treated with recombinant TGF-beta1 for 0-6 days. Activities of the EMT regulators, Snail and Slug, and of extracellular hallmarks, MMP2 and 9, were detected using real-time PCR and Western blots. An in vitro wound healing assay then assessed short-term EMT, whilst phenotypic changes associated with the above gene expressions were evaluated by immunocytochemistry. Results showed that Slug and MMP9 were up-regulated at both mRNA and protein levels, while Snail expression rose and fell, in concert with expression of MMP2. In the wound healing assay, Snail was seen alone at the invasive front in SCC9 and SCC15 cultures, while both Snail and Slug appeared at wound margins in SCC25. Both MMP2 and MMP9 were detected at wound edges in all cell lines, with MMP2 localised in cell nuclei, MMP9 was restricted to the cytoplasm. The study suggests that both Snail and Slug act as regulators of TGF-beta1-trigged EMT in OSCC cells. Snail may up-regulate MMP2 or MMP9 initiating EMT, while Slug may share a role with Snail in maintaining longer-term EMT, by stimulating MMP9 expression. 

Retracted: No

PubPeer comments:
 Figure 2 appears to have some overlapping images (Edit: Figure in next comment) , 
 ![file] , 
 #2 ![file] ,
Local and Global Influences of Visual Spatial Selection and Locomotion in Mouse Primary Visual Cortex
Authors: Su-Yee J Lee
Ethan G McBride
Edward M Callaway
Journal: Current Biology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: behavior; electrophysiology; locomotion; mouse; neuroscience
Affiliations: Systems Neurobiology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA., Systems Neurobiology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Systems Neurobiology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: .

Abstract:  Sensory selection and movement locally and globally modulate neural responses in seemingly similar ways. For example, locomotion enhances visual responses in mouse primary visual cortex (V1), resembling the effects of spatial attention on primate visual cortical activity. However, interactions between these local and global mechanisms and the resulting effects on perceptual behavior remain largely unknown. Here, we describe a novel mouse visual spatial selection task in which animals either monitor one of two locations for a contrast change ("selective mice") or monitor both ("non-selective mice") and can run at will. Selective mice perform well only when their selected stimulus changes, giving rise to local electrophysiological changes in the corresponding hemisphere of V1 including decreased noise correlations and increased visual information. Non-selective mice perform well when either stimulus changes, giving rise to global changes across both hemispheres of V1. During locomotion, selective mice have worse behavioral performance, increased noise correlations in V1, and decreased visual information, while non-selective mice have decreased noise correlations in V1 but no change in performance or visual information. Our findings demonstrate that mice can locally or globally enhance visual information, but the interaction of the global effect of locomotion with local selection impairs behavioral performance. Moving forward, this mouse model will facilitate future studies of local and global sensory modulatory mechanisms and their effects on behavior. 

Retracted: No

PubPeer comments:
 Figure 3 and Figure 7 have exactly the same left panels. ![file] ,
GM1 and tumor necrosis factor-alpha, overexpressed in renal cell carcinoma, synergize to induce T-cell apoptosis
Authors: Ronald Bukowski
Daisuke Kudo
Brian Rini
Gaurisankar Sa
Luis Molto
Kaushik Biswas
Cynthia Hilston
Tanya Das
James H Finke
Patricia Rayman
Charles Tannenbaum
Journal: Cancer Research (2008)
Discipline: CLINICAL MEDICINE
Keywords: T-cell apoptosis; tumors; immune system evasion; gangliosides; TNFalpha
Affiliations: Molecular Medicine Division, Bose Institute, Kolkata, India.

Abstract:  The ability to induce T-cell apoptosis is one mechanism by which tumors evade the immune system, although the molecules involved remain controversial. We found that renal cell carcinoma (RCC)-induced T-cell apoptosis was inhibited by &gt;50% when cocultures were performed with ganglioside-depleted tumor cells, caspase-8-negative lymphocytes, or anti-tumor necrosis factor-alpha (TNFalpha) antibodies, suggesting that tumor gangliosides synergize with signals delivered through TNFalpha death receptors to mediate T-cell killing. The synergy between tumor-derived TNFalpha and the RCC-overexpressed ganglioside GM1 for killing resting T cells is corroborated by studies using purified GM1 and rTNF alpha, which indicate that a 48-hour pretreatment with the ganglioside optimally sensitizes the lymphocytes to a TNFalpha-induced apoptotic death. However, activated T cells, which synthesize TNFalpha themselves, can be killed by exogenous GM1 alone. RelA-overexpressing lymphocytes are protected from GM1 plus TNFalpha-mediated apoptosis, a finding consistent with our previous studies indicating that gangliosides inhibit nuclear factor-kappaB activation. These results are clinically relevant because, similar to T-cells cocultured with GM1-overexpressing RCC lines, T cells isolated from the peripheral blood of patients with metastatic RCC are also heavily coated with that tumor-shed ganglioside. This population of patient cells, unlike T cells isolated from normal donors, is highly susceptible to apoptosis induced by rTNF alpha or by metastatic patient sera, which contain elevated levels of the cytokine. This report thus extends our previous studies by demonstrating that tumor-derived TNFalpha enhances RCC apoptogenicity not only by inducing ganglioside synthesis but also by initiating receptor-dependent apoptosis in T cells in which the nuclear factor-kappaB activation pathway has been inhibited by GM1. 

Retracted: No

PubPeer comments:
 Fig3 ![file] Fig 6 ![file] The control cells in Fig 3C and 6A are same, however the subsequent staining is different. In Fig 3C, the normal T cells were incubated with GM1 whereas Fig 6A says peripheral blood T-cells isolated from healthy donors and patients with RCC. How can the same set of normal T cells be treated differently? Also unsure whether the cells showing in Fig 3A is from patient or cultured cells. Could authors clarify? ,
Pharmacotherapy with fluoxetine restores functional connectivity from the dentate gyrus to field CA3 in the Ts65Dn mouse model of down syndrome
Authors: Jacopo Magistretti
Laura Calzà
Chiara Mangano
Fiorenza Stagni
Elisabetta Ciani
Renata Bartesaghi
Sandra Guidi
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Down syndrome; cognitive impairment; hippocampus; long-term memory; neurogenesis
Affiliations: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Abstract:  Down syndrome (DS) is a high-incidence genetic pathology characterized by severe impairment of cognitive functions, including declarative memory. Impairment of hippocampus-dependent long-term memory in DS appears to be related to anatomo-functional alterations of the hippocampal trisynaptic circuit formed by the dentate gyrus (DG) granule cells - CA3 pyramidal neurons - CA1 pyramidal neurons. No therapies exist to improve cognitive disability in individuals with DS. In previous studies we demonstrated that pharmacotherapy with fluoxetine restores neurogenesis, granule cell number and dendritic morphology in the DG of the Ts65Dn mouse model of DS. The goal of the current study was to establish whether treatment rescues the impairment of synaptic connectivity between the DG and CA3 that characterizes the trisomic condition. Euploid and Ts65Dn mice were treated with fluoxetine during the first two postnatal weeks and examined 45-60 days after treatment cessation. Untreated Ts65Dn mice had a hypotrophyc mossy fiber bundle, fewer synaptic contacts, fewer glutamatergic contacts, and fewer dendritic spines in the stratum lucidum of CA3, the terminal field of the granule cell projections. Electrophysiological recordings from CA3 pyramidal neurons showed that in Ts65Dn mice the frequency of both mEPSCs and mIPSCs was reduced, indicating an overall impairment of excitatory and inhibitory inputs to CA3 pyramidal neurons. In treated Ts65Dn mice all these aberrant features were fully normalized, indicating that fluoxetine can rescue functional connectivity between the DG and CA3. The positive effects of fluoxetine on the DG-CA3 system suggest that early treatment with this drug could be a suitable therapy, possibly usable in humans, to restore the physiology of the hippocampal networks and, hence, memory functions. 

Retracted: No

PubPeer comments:
 Figure 3A. GAPDH panel. Low resolution, but much more similar than you would expect, especially lanes 2 and 4. https: imgur.com ygPXN6y Same goes for figure 4A. , 
 Figure 4A. Much more similar than you would expect. https: imgur.com U4NpQKG ,
The role of human papillomavirus genotyping for detecting high-grade intraepithelial neoplasia or cancer in HPV-positive women with normal cytology: a study from a hospital in northeastern China
Authors: Danbo Wang
Jing Zhang
Xiaobin Wang
Zhuo Yang
Deyu Zhang
Journal: BMC Cancer (2020)
Discipline: CLINICAL MEDICINE
Keywords: Cervical cancer; HPV genotyping; High-grade squamous intraepithelial lesion; Human papillomavirus; hrHPV prevalence.
Affiliations: Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No.44 Xiaoheyan Road, Shenyang, 110042, Liaoning province, China., Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No.36 Sanhao Street, Shenyang, 110004, Liaoning province, China., Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No.44 Xiaoheyan Road, Shenyang, 110042, Liaoning province, China. .

Abstract:  Background: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting cervical cancer and its precursors. This study aimed to analyze the prevalence of high-risk HPV genotypes and evaluate the role of HPV genotyping triage for detecting high-grade squamous intraepithelial lesions, adenocarcinoma in situ and cervical cancer (HSIL+) in HPV-positive women with normal cytology. Methods: A retrospective study was performed in women who had undergone co-screening at the China Medical University-affiliated Shengjing Hospital between 2012 and 2014. Results: Of the 34,587 women, 2665 HPV-positive women with normal cytology who had received colposcopy were eligible for analysis. In HSIL+ groups of 204 women, the common genotypes were HPV16, HPV52, HPV58, HPV33, HPV31 and HPV18 in order of prevalence. The proportion of histological HSIL+ in women infected with HPV33 or HPV31 was not significantly different compared to women infected with HPV16 (P = 0.30, P = 0.19, respectively). The odds ratios for histological HSIL+ were 3.26 (95% confidence interval [CI]: 2.41-4.40) in women with HPV16/18, 4.21 (95% CI: 2.99-5.93) in those with HPV16/18/31/33, and 5.73 (95% CI: 3.30-9.97) in those with HPV16/18/31/33/52/58. Including HPV31/33 genotyping together with HPV16/18 significantly increased the proportion of HSIL+ detection from 63.2 to 77.5% (P = 0.002) without significantly increasing the colposcopy per HSIL+ detection ratio (7.7 to 8.1, P = 0.66). Conclusions: HPV genotyping played an important role in managing HPV-positive women with normal cytology. Genotyping for HPV31/33 should be added to the previously recommended HPV16/18 genotyping in triaging HPV-positive women in northeastern China. 

Retracted: No

PubPeer comments:
 The value of n at the top of the table is not equal to the sum of the numbers at the bottom. ![file] , 
 #1 Thank you for your attention. The data in the table seems to be not equal, because some patients have multiple HPV infections. We have indicated at the bottom of the table that  Women with multiple HPV types detected are counted to each type, and therefore counted more than once . I hope it will not cause misunderstanding to readers ,
Substitutes for endangered medicinal animal horns and shells exposed by antithrombotic and anticoagulation effects
Authors: Xiaoping Dong
Da Zhang
Dan Yan
Xiaohe Xiao
Yan Yan
Xue Feng
Jiaoyang Luo
Journal: Journal of Ethnopharmacology (2011)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cornu Saigae Tataricae; Manis Squama; Cornu Cervi Pantotrichum; Cornu Bovis grunniens; medicinal animal horns and shells
Affiliations: China Military Institute of Chinese Meteria Medica, Military 302 Hospital, Beijing 100039, China.

Abstract:  Aim of the study: Cornu Saigae Tataricae (antelope horn), Manis Squama (pangolin scale), Cornu Cervi Pantotrichum (velvet antler) and Cornu Bovis grunniens (yak horn) are valuable medicinal animal horns and shells (MAHS). As the major source of biological agents and ethnodrugs, MAHS show pretty good bioactivities. However, with the increased demand for MAHS, some of the medicinal resources are endangered, and there has been a concomitant increase in the prevalence of adulterated or impostor MAHS. It is of great significance to exploit the substitutes for endangered medicinal animal resources. This study is going to provide a new mode for the exploitation of the substitutes of MAHS. Materials and methods: Plasma recalcification time, thrombin time and thrombin consumption were recorded to evaluate the anticoagulation effect of MAHS. Dissolution rate of thrombus in vitro and whole blood-gore were observed to appraise the antithrombotic effect of MAHS. Results: All the MAHS involved in this study except Cornu Procaprae Gutturosae (argali horn), Cornu Saigae Tataricae and Cornu Bovis (cattle horn) could not only prolong recalcification time (P&lt;0.01) and thrombin time (P&lt;0.01), but also dissolve the thrombus in vitro (P&lt;0.01) and whole blood-gore (P&lt;0.01). The bioactivities among MAHS differed greatly from each other. Conclusions: The results indicate that Cornu Caprae Hircus (goat horn), Cornu Bubali (water buffalo horn) and Trionycis Carapax (turtle shell) are rational to be explored as the substitutes of Cornu Saigae Tataricae, Cornu Bovis grunniens and Manis Squama, respectively. On the contrary, velvet antler is not suitable to be substituted by Cornu Cervi (deerhorn). We presume that the bioactive evaluation methods are effective means of seeking substitutive resources of endangered medicinal animals with the advantages of close correlation to drug action, low dosage, and high sensitiveness. 

Retracted: No

PubPeer comments:
  Materials and methods: Plasma recalcification time, thrombin time and thrombin consumption were recorded to evaluate the anticoagulation effect of MAHS. Dissolution rate of thrombus in vitro and whole blood-gore were observed to appraise the antithrombotic effect of MAHS.  Could the authors explain what  whole blood-gore means in this context? ,
Epigenetic control of HNF-4α in colon carcinoma cells affects MUC4 expression and malignancy
Authors: Irena Peri
Anna Algamas-Dimantov
Betty Schwartz
Einav Yehuda-Shnaidman
Journal: Cellular Oncology (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HNF-4α; HDAC inhibitors; proliferation; colon carcinoma; gene expression
Affiliations: Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot, 76100, Israel.

Abstract:  Background: We previously found that enhanced expression of hepatocyte nuclear factor 4α (HNF-4α) is associated with hyper-proliferation of colon carcinoma cells. Here, the effect of histone deacetylase (HDAC) inhibitors on proliferation and the expression of HNF-4α and its downstream target genes were assessed in HM7, LS174T, HT29 and Caco-2 colon carcinoma cell lines. Results: HNF-4α expression was found to vary in the different colon carcinoma cell lines tested, being highest in HM7. Additionally, a direct correlation with proliferation was observed. In HM7 cells, the weak HDAC inhibitor butyrate significantly inhibited the transcription of HNF-4α, its downstream target gene MUC4, and genes associated with proliferation, including the proliferating cell nuclear antigen gene PCNA. siRNA-mediated silencing of HNF-4α exerted an effect similar to butyrate on HM7 cell proliferation. The stronger HDAC inhibitor trichostatin A (TSA) exerted an effect similar to that of siRNA-mediated HNF-4α silencing and, concomitantly, inhibited the expression of the transcription factor gene SP1. Also, siRNA-mediated silencing of HDAC3 and HDAC4 reduced HNF-4α expression. Chromatin immunoprecipitation (ChIP) assays revealed that TSA induces hyperacetylation of histones H3 and H4 and, concomitantly, inhibits SP1 binding to the HNF-4α promoter. Subsequent electromobility shift assays supported these latter findings. Conclusions: HNF-4α transcriptional expression and activity are tightly controlled by epigenetic mechanisms. HDAC inhibitor targeting of HNF-4α may serve as an effective treatment for advanced colon carcinomas, since downstream cancer-associated target genes such as MUC4 are significantly down-regulated by this treatment. 

Retracted: No

PubPeer comments:
 Figure 1D. * Red boxes: The right-most two lanes of the HNF-4a panel look similar to each other. ![file] , 
 Figure 2B. * Blue boxes: The HNF-4a and PCNA panels look more similar than expected. ![file] , 
 Figure 4B. * The HNF-4a panel appears to show a vertical splice between the 2nd and 3rd lane not observed in other blots of these experiments. * The MUC-4 panels has five bands, while representing only four samples. ![file] , 
 Figure 6E. Made a bit lighter to bring out details. * Green boxes: The right H3 and H4 panels, in particular the first lanes, look very similar to each other. ![file] ,
The NS5A protein of the hepatitis C virus genotype 1a is cleaved by caspases to produce C-terminal-truncated forms of the protein that reside mainly in the cytosol
Authors: Maria Kalamvoki
Urania Georgopoulou
Penelope Mavromara
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NS5A protein; hepatitis C virus; caspase proteases; cleavage sites; Asp154
Affiliations: Molecular Virology Laboratory, Hellenic Pasteur Institute, 115 21 Athens, Greece.

Abstract:  The nonstructural 5A (NS5A) protein of the hepatitis C virus (HCV) is a multifunctional protein that is implicated in viral replication and pathogenesis. We report here that NS5A of HCV-1a is cleaved at multiple sites by caspase proteases in transfected cells. Two cleavage sites at positions Asp154 and 248DXXD251 were mapped. Cleavage at Asp154 has been previously recognized as one of the caspase cleavage sites for the NS5A protein of HCV genotype 1b (1, 2) and results in the production of a 17-kDa fragment. The sequence 248DXXD251 is a novel caspase recognition motif for NS5A and is responsible for the production of a 31-kDa fragment. Furthermore, we show that Arg217 is implicated in the production of the previously described 24-kDa product, whose accumulation is affected by both calpain and caspase inhibitors. We also showed that caspase-mediated cleavage occurs in the absence of exogenous proapoptotic stimuli and is not related to the accumulation of the protein in the endoplasmic reticulum. Interestingly, our data indicate that NS5A is targeted by at least two different caspases and suggest that caspase 6 is implicated in the production of the 17-kDa fragment. Most importantly, we report that, all the detectable NS5A fragments following caspase-mediated cleavage are C-terminal-truncated forms of NS5A and are mainly localized in the cytosol. Thus, in sharp contrast to the current view we found no evidence supporting a role for caspase-mediated cleavage in the transport of the NS5A protein to the nucleus, which could lead to transcriptional activation. 

Retracted: No

PubPeer comments:
 ![file] ,
Hypoxia inducible factor-1α/vascular endothelial growth factor signaling activation correlates with response to radiotherapy and its inhibition reduces hypoxia-induced angiogenesis in lung cancer
Authors: Hongjun Zhu
Shuanglin Zhang
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: angiogenesis; hypoxia; hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway; lung cancer; resistance to radiotherapy.
Affiliations: Department of Thoracic Surgery, Shangqiu First People's Hospital, Shangqiu, Henan, China., Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Henan University, Kaifeng, China.

Abstract:  Like other tumors, lung cancer must induce angiogenesis as it grows. Hypoxia-inducible factor 1α (HIF-1α) is the inducible subunit of the HIF-1 transcription factor that regulates genes involved in the response to hypoxia, some of which contributes to angiogenesis. Vascular endothelial growth factor (VEGF) is one of the genes upregulated by HIF-1 and is the primary cytokine in relation to angiogenesis. In this study we tested whether aberrant activation of hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway correlates with response to radiotherapy and examined the response of lung cancer cells to hypoxia in vitro. We determined increased expressions of HIF-1α and VEGF-A in 76 cancerous tissues of responders (complete remission and partial remission). HIF-1α and VEGF-A were shown to be upregulated in lung cancer cells in response to hypoxia. The treatment with anti-HIF-1α siRNA prior to hypoxia exposure was shown to decrease HIF-1α and VEGF-A expressions and reduce hypoxia-induced angiogenesis, suggesting that HIF-1α expression resulted in increased VEGF-A expression and activation of HIF-1α/VEGF pathway was responsible for hypoxia-induced angiogenesis. In conclusion, we identified the relationship between HIF-1α/VEGF pathway and response to radiotherapy and its role in angiogenesis in lung cancer in vitro. HIF-1α/VEGF pathway as a target for antiangiogenic treatment strategies for this tumor requires further investigation. 

Retracted: No

PubPeer comments:
 Fig 8A.  Cell invasion of 4 Gy Xu2010ray irradiated cells detected by Transwell assay among the normoxia, hypoxia, hypoxia + siNC and hypoxia + siHIFu20101u03b1 groups. Notes: (A) the cells passing through from the upper chamber into the bottom chamber under the microscope . ![file] I have a concern. , 
 Fig 7C.  Cells apoptosis of 4 Gy Xu2010ray irradiated cells among the normoxia, hypoxia, hypoxia + siNC and hypoxia + siHIFu20101u03b1 groups.... (C) TUNELu2010positive cells under the optical microscope . ![file] Another concern. ,
Antidiabetes and antiobesity effect of cryptotanshinone via activation of AMP-activated protein kinase
Authors: Kun Ho Son
Sung-Soo Kim
Wonchae Choe
Seung-Nam Jung
Sung Ran Kim
Joohun Ha
Myoung Gyu Park
Tae Youl Ha
Jong Guk Park
In Gun Jo
Eun Ju Kim
Journal: Molecular Pharmacology (2007)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Metabolic disorders; type 2 diabetes; obesity; AMP-activated protein kinase (AMPK); therapeutic target
Affiliations: Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species, Kyung Hee University School of Medicine, Seoul, Korea.

Abstract:  Metabolic disorders, including type 2 diabetes and obesity, represent major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK has been demonstrated to mediate, at least in part, the effects of a number of physiological and pharmacological factors that exert beneficial effects on these disorders. Thus, the identification of a compound that activates the AMPK pathway would contribute significantly to the treatment and management of such syndromes. In service of this goal, we have screened a variety of naturally occurring compounds and have identified one compound, cryptotanshinone, as a novel AMPK pathway activator. Cryptotanshinone was originally isolated from the dried roots of Salvia militorrhiza, an herb that is used extensively in Asian medicine and that is known to exert beneficial effects on the circulatory system. For the first time, in the present study, we have described the potent antidiabetic and antiobesity effects of cryptotanshinone, both in vitro and in vivo. Our findings suggest that the activation of the AMPK pathway might contribute to the development of novel therapeutic approaches for the treatment of metabolic disorders such as type 2 diabetes and obesity. 

Retracted: No

PubPeer comments:
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Antitumor Effects of 8-Deoxylactucin in RB355 Human Retinoblastoma Cells Are Mediated via Apoptosis Induction, Reactive Oxygen Species Production, and Cell Cycle Arrest
Authors: Yu Jinhai
Li Yue
Tan Guiying
Xiong Chao
Xu Qihua
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: Retinoblastoma; 8-deoxylactucin; Anticancer effects; RB355 cells; Normal cells
Affiliations: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi, China (mainland)

Abstract:  BACKGROUND Retinoblastoma is a rare malignancy arising from the immature cells of the retina, generally in children up to the age of 3 years. Here, we assessed the anticancer effects of a natural sesquiterpene lactone - 8-deoxylactucin - on the growth of the retinoblastoma RB355 and normal RPE cells. MATERIAL AND METHODS Cell viability was assessed by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was assessed by DAPI staining and annexin V/propidium iodide (PI) assay. Reactive oxygen species (ROS) levels were determined by fluorescence microscopy. Flow cytometry was used to determine the cell cycle distribution. Protein expression was determined by Western blot analysis. RESULTS The results showed that 8-deoxylactucin exerted selective and potent anticancer effects on the RB355 cells and exhibited an IC50 of 25 µM. Nonetheless, the cytotoxic effects of 8-deoxylactucin on the normal RPF cells were comparatively lower, as evident from the IC₅₀ of 65 µM. 8-Deoxylactucin increased the production of ROS and triggering apoptosis of RB355 cells. The induction of 8-deoxylactucin-induced apoptosis was also accompanied with increased cleavage of caspase 3, upregulation of Bax, and downregulation of Bcl-2. The 8-deoxylactucin-induced cell cycle arrest of RB355 cells was also associated with inhibition of cyclin A and B1 expression, as well as the inhibition of Cdc2 phosphorylation. CONCLUSIONS 8-Deoxylactucin inhibits the growth of RB355 cells by apoptosis, cell cycle arrest, and increased production of ROS. 

Retracted: Yes

PubPeer comments:
 Figure 3.  DAPI ... staining showing induction of apoptosis in the retinoblastoma RB355 cells at the indicated concentrations of 8-deoxylactucin . Two panels overlap, and are unlikely to represent different concentrations. ![file] , 
 *[right]* Figure 6.  Enhancement in the production of ROS in the RB355 retinoblastoma cells upon treatment with indicated concentrations of 8-deoxylactucin. *[left]* Figure 4B from [Huang, Xie Liu (2019)] .  Effect of Icariin at indicated concentrations on... (B) MMP levels of HeLa cells as determined by fluorescence microscopy. The figure depicts that ... the MMP levels decrease in HeLa cells upon treatment with Icariin . ![file] , 
 Retracted [25 March 2021] .  An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. ,
RhoC interacts with integrin α5β1 and enhances its trafficking in migrating pancreatic carcinoma cells
Authors: Yongwei Yu
Ian R Hart
Ningfeng Fiona Li
Francis J Marshall
Christine Iacobuzio-Donahue
Emilios Gemenetzidis
Derek Davies
Adam K Woolf
David A Tuveson
Yoshiki Naito
Roger M Feakins
Fieke E M Froeling
Hemant M Kocher
Kristopher Frese
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Pancreatic ductal adenocarcinoma; RhoC; cancer cell migration; invasion; integrin α5β1
Affiliations: Barts Cancer Institute - a CR-United Kingdom Centre of Excellence, Queen Mary University of London, Centre for Tumour Biology, London, United Kingdom.

Abstract:  Human pancreatic ductal adenocarcinoma (PDAC) is characterized by early systemic dissemination. Although RhoC has been implicated in cancer cell migration, the relevant underlying molecular mechanisms remain unknown. RhoC has been implicated in the enhancement of cancer cell migration and invasion, with actions which are distinct from RhoA (84% homology), and are possibly attributed to the divergent C-terminus domain. Here, we confirm that RhoC significantly enhances the migratory and invasive properties of pancreatic carcinoma cells. In addition, we show that RhoC over-expression decreases cancer cell adhesion and, in turn, accelerates cellular body movement and focal adhesion turnover, especially, on fibronectin-coated surfaces. Whilst RhoC over-expression did not alter integrin expression patterns, we show that it enhanced integrin α5β1 internalization and re-cycling (trafficking), an effect that was dependent specifically on the C-terminus (180-193 amino acids) of RhoC protein. We also report that RhoC and integrin α5β1 co-localize within the peri-nuclear region of pancreatic tumor cells, and by masking the CAAX motif at the C-terminal of RhoC protein, we were able to abolish this interaction in vitro and in vivo. Co-localization of integrin α5β1 and RhoC was demonstrable in invading cancer cells in 3D-organotypic cultures, and further mimicked in vivo analyses of, spontaneous human, (two distinct sources: operated patients and rapid autopsy programme) and transgenic murine (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre), pancreatic cancers. In both cases, co-localization of integrin α5β1 and RhoC correlated with poor differentiation status and metastatic potential. We propose that RhoC facilitates tumor cell invasion and promotes subsequent metastasis, in part, by enhancing integrin α5β1 trafficking. Thus, RhoC may serve as a biomarker and a therapeutic target. 

Retracted: No

PubPeer comments:
 Figure 5E. Much more similar than expected. ![file] ,
Adenovirus-mediated overexpression of BMP-9 inhibits human osteosarcoma cell growth and migration through downregulation of the PI3K/AKT pathway
Authors: Shengdan Jiang
Binbin Ni
Yuehua Yang
Bo Li
Leisheng Jiang
Ke Chen
Journal: International Journal of Oncology (2012)
Discipline: CLINICAL MEDICINE
Keywords: Bone morphogenetic proteins (BMPs); osteosarcoma progression; BMP-9; cell growth; migration
Affiliations: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, PR China.

Abstract:  Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily of signaling molecules and have previously been shown to be associated with the biological behavior of osteosarcoma. However, to date the effects and molecular mechanisms of BMP-9 on osteosarcoma progression are unknown. We performed real-time PCR and western blot analysis to characterize the endogenous expression of BMP-9 in osteosarcoma cell lines. We used a recombinant adenovirus expressing BMP-9 (adBMP-9) to infect osteosarcoma cell lines with relatively low endogenous BMP-9 expression to determine the functional relevance of BMP-9 overexpression to osteosarcoma cell growth and migration in vitro and in vivo, and further investigated the expression levels of Ki-67, matrix metallopeptidase-9 (MMP-9), phosphoinositide 3-kinase p85α (PI3Kp85α) and phosphorylated AKT (p-AKT). As a result, osteosarcoma cell proliferation and migration were significantly diminished by adBMP-9, indicated by MTT and wound-healing assays, and cell apoptosis was markedly induced, indicated by Hoechst 33342/PI assay and Annexin V-FITC apoptosis detection. When BMP-9 expression was enhanced, the expression of PI3Kp85α, p-AKT, Ki-67 and MMP-9 was downregulated in osteosarcoma cells. In addition, the tumor volumes in MG-63 and HOS subcutaneous nude mouse models treated with adBMP-9 were significantly smaller compared to those of the ad-GFP group. These results suggested that the enhanced expression of BMP-9 in osteosarcoma cells by adBMP-9 exerted inhibitory effects on growth and migration of osteosarcoma cells possibly via blockade of the PI3K/AKT signaling pathway. 

Retracted: No

PubPeer comments:
 This paper has a 2016 correction which reads:  Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of the western blots in Fig. 4B and C. These contained the same GAPDH control data, even though Fig. 4B and C were intended to show the inhibition of osteosarcoma cell migration by a recombinant adenovirus (ad) expressing bone morphogenetic protein 9 (adBMP-9) in two different cell lines, MG-63 and HOS, respectively. After having re-examined our original data, we realize that the same GAPDH control bands were inadvertently selected for Fig. 4B and C. A corrected version of Fig. 4, containing alternative data obtained from the experiments performed in duplicate, is presented below.  Here is the original Figure 4 with the duplication marked in red: ![file] ,