RESUMO
Retraction statement. We, the Editors and Publisher of Journal of Biological Regulators and Homeostatic Agents, have retracted the following article: "miR-1290 promotes proliferation and suppresses apoptosis in acute myeloid leukemia by targeting FOXG1/SOCS3". Published in our Vol. 33 n. 6, 2019 issue, DOI: 10.23812/19-189-A. The article has been retracted following receipt of information from the corresponding author X.L. Ju, informing us that "they found that the cell lines they had been experimenting with were contaminated, and some of the results could not be repeated. In order not to mislead readers, they have withdrawn this manuscript with apologies". The article is withdrawn from all print and electronic editions.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted."
Assuntos
Apoptose , Proliferação de Células , Fatores de Transcrição Forkhead/metabolismo , Leucemia Mieloide Aguda/genética , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Linhagem Celular Tumoral , Células HL-60 , Humanos , Leucemia Mieloide Aguda/patologiaRESUMO
Retraction statement. We, the Editors and Publisher of Journal of Biological Regulators and Homeostatic Agents, have retracted the following article: "miR-1290 promotes proliferation and suppresses apoptosis in acute myeloid leukemia by targeting FOXG1/SOCS3". Published in our Vol. 33 n. 6, 2019 issue, DOI: 10.23812/19-189-A. The article has been retracted following receipt of information from the corresponding author X.L. Ju, informing us that "they found that the cell lines they had been experimenting with were contaminated, and some of the results could not be repeated. In order not to mislead readers, they have withdrawn this manuscript with apologies". The article is withdrawn from all print and electronic editions.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted."
RESUMO
According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, antibiotic resistance escalates more challenges in treatment against communicable diseases worldwide. Henceforth, the use of combinational antimicrobial therapy and metal-conjugated phytoconstituents composites are considered as alternatives. The present study explored the efficacy of mercuric-sulfide-based metallopharmaceutical, Sivanar Amirtham for anti-bacterial, anti-tuberculosis, anti-HIV therapeutics and toxicity profile by haemolytic assay, first of its kind. The anti-bacterial study was performed against both gram-positive and gram-negative pathogens including Staphylococcus aureus (ATCC 29213), Methicillin-resistant Staphylococcus aureus (MRSA: ATCC 43300), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (PA14) and Vibrio cholerae (MTCC 3905) by agar well diffusion assay, wherein the highest zone of inhibition was identified for MRSA (20.7 mm) and V. cholerae (34.3 mm) at 25 mg/mL. Furthermore, the anti-tuberculosis activity experimented by microtitre alamar blue assay against M. tuberculosis (ATCC 27294) demonstrated significant activity at the concentration range of 12.5-100 µg/mL. Additionally, the anti-HIV efficacy established by the syncytia inhibition method using C8166 cell lines infected with HIV-1IIIB, showed a significant therapeutic effect. The in-vitro toxicity assay proved Sivanar Amirtham to be non-haemolytic and haemocompatible. The physicochemical characterization studies revealed the nano-sized particles with different functional groups and the distinctive metal-mineral complex could be attributed to the multi-site targeting ability. The rationale evidence and scientific validation for the efficacy of Sivanar Amirtham ensures that it could be proposed as an alternative or adjuvant for both prophylactics and therapeutics to overcome HIV infection and antimicrobial resistance as well as the multi-drug resistance challenges.
Assuntos
Infecções por HIV , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana Múltipla , Sulfetos/farmacologiaRESUMO
Objective: To explore the clinical characteristics, treatment methods and outcomes of extramedullary plasmacytoma of the head and neck. Methods: A retrospective analysis was conducted on 10 cases with extramedullary plasmacytoma of the head and neck who were admitted to Henan Tumor Hospital from January 2005 to January 2020. Among the 10 patients, 6 were male and 4 were female. The average age at diagnosis was 56.3 years old (34-74 years old). Among them, 3 cases were located in the nasal cavity, 2 cases in the nasopharynx, 1 case in the sinuses, 2 cases in the larynx, 1 case in the oropharynx, and 1 case in the cervical lymph nodes. Treatments were administered according to tumor size and resection extent. Complete surgical excision (negative margins) was preferred, followed by adjuvant radiotherapy or radiotherapy alone. The clinical characteristics, diagnosis, treatment and prognosis of EMP were analyzed. Results: The patients' symptoms were not specific, frequently with local obstruction symptom and localized masses. All patients were confirmed pathologically as suffering from monoclonal plasmacytoma, with negative bone marrow biopsy and negative skeletal survey. Five patients received surgery, 3 received radiotherapy, and 2 received surgery with additional radiation. The follow-up time was 16-125 months, with a median of 92 months. Two patients developed into multiple myeloma. One patient who received radiotherapy after surgery relapsed after 7 years of follow-up and again received surgical treatment, with no evidence of second recurrence. The remaining patients had no recurrence or progression. Conclusion: Extramedullary plasmacytoma of the head and neck has a good prognosis. Surgical treatment can be considered for completely resectable lesions.
Assuntos
Neoplasias de Cabeça e Pescoço , Mieloma Múltiplo , Plasmocitoma , Adulto , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Plasmocitoma/diagnóstico , Plasmocitoma/patologia , Plasmocitoma/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
Inhibitors of IMP dehydrogenase, such as mycophenolic acid (MPA) and mizoribine, which deplete cellular GTP, are used clinically as immunosuppressive drugs. The prolonged effect of such agents on insulin-secreting beta-cells (HIT-T15 and INS-1) was investigated. Both MPA and mizoribine inhibited mitogenesis, as reflected by [3H]thymidine incorporation. Cell number, DNA and protein contents, and cell (metabolic) viability were decreased by about 30%, 60%, and 80% after treatment of HIT cells with clinically relevant concentrations (e.g. 1 microg/ml) of MPA for 1, 2, and 4 days, respectively. Mizoribine (48 h) similarly induced the death of HIT cells. INS-1 cells also were damaged by prolonged MPA treatment. MPA-treated HIT cells displayed a strong and localized staining with a DNA-binding dye (propidium iodide), suggesting condensation and fragmentation of DNA, which were confirmed by detection of DNA laddering in multiples of about 180 bp. DNA fragmentation was observed after 24-h MPA treatment and was dose dependent (29%, 49%, and 70% of cells were affected after 48-h exposure to 1, 3, and 10 microg/ml MPA, respectively). Examination of MPA-treated cells by electron microscopy revealed typical signs of apoptosis: condensed and marginated chromatin, apoptotic bodies, cytosolic vacuolization, and loss of microvilli. MPA-induced cell death was almost totally prevented by supplementation with guanosine, but not with adenosine or deoxyguanosine, indicating a specific effect of GTP depletion. An inhibitor of protein isoprenylation (lovastatin, 10-100 microM for 2-3 days) induced cell death and DNA degradation similar to those induced by sustained GTP depletion, suggesting a mediatory role of posttranslationally modified GTP-binding proteins. Indeed, impeding the function of G proteins of the Rho family (via glucosylation using Clostridium difficile toxin B), although not itself inducing apoptosis, potentiated cell death induced by MPA or lovastatin. These findings indicate that prolonged depletion of GTP induces beta-cell death compatible with apoptosis; this probably involves a direct impairment of GTP-dependent RNA-primed DNA synthesis, but also appears to be modulated by small GTP-binding proteins. Treatment of intact adult rat islets (the beta-cells of which replicate slowly) induced a modest, but definite, death by apoptosis over 1- to 3-day periods. Thus, more prolonged use of the new generation of immunosuppressive agents exemplified by MPA might have deleterious effects on the survival of islet or pancreas grafts.
Assuntos
Apoptose/fisiologia , Proteínas de Bactérias , Guanosina Trifosfato/deficiência , Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Animais , Apoptose/efeitos dos fármacos , Toxinas Bacterianas/farmacologia , Proteínas de Ligação ao GTP/fisiologia , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Lovastatina/farmacologia , Mitose/fisiologia , Ácido Micofenólico/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Adenine nucleotides play an important role in the control of membrane potential by acting on ATP-sensitive K+ (K(ATP)) channels and, in turn, modulating the open probability of voltage-gated Ca2+ channels in pancreatic islet beta-cells. Here, we provide evidence that guanine nucleotides (GNs) also may be involved in the modulation of these events in vivo. GNs were depleted by treatment of HIT-T15 cells with mycophenolic acid (MPA). Resting membrane potential was more depolarized in cells treated for 3 and 6 hr with MPA than in control cells, and this effect was inhibited by diazoxide. After 6 hr of exposure to MPA, basal cytosolic free Ca2+ concentrations ([Ca2+]i) were elevated by 20%. Increments in [Ca2+]i induced by submaximal concentrations of K+ (10-15 mM) or bombesin were enhanced by > 50%. Opening K(ATP) channels with diazoxide lowered basal [Ca2+]i in MPA-treated cells to normal and abrogated the enhanced [Ca2+]i responses. However, an L-type Ca2+ channel blocker only abolished the enhanced [Ca2+]i response to stimuli and had no effect on the elevated basal [Ca2+]i, in contrast to EGTA, which obliterated both, implying that the latter was due to Ca2+ influx via non-L-type Ca2+ channels. These effects on ion fluxes were attributable specifically to GN depletion, since guanosine, which restores GTP content and the GTP/GDP ratio, but not adenosine, prevented all MPA-induced ion changes; furthermore, the latter were mimicked by mizoribine (a structurally dissimilar GTP synthesis inhibitor). It is concluded that, in addition to adenine nucleotides, GNs might contribute to the modulation of K(ATP) channels in intact beta-cells. In addition, GN depletion appeared to be able to reduce stimulated insulin secretion by a mechanism largely independent of the changes of ion fluxes observed above.
Assuntos
Cálcio/metabolismo , Nucleotídeos de Guanina/fisiologia , Insulina/metabolismo , Ilhotas Pancreáticas/fisiologia , Animais , Células Cultivadas , Cricetinae , Citosol/efeitos dos fármacos , Citosol/fisiologia , Diazóxido/farmacologia , Inibidores Enzimáticos/farmacologia , Nucleotídeos de Guanina/biossíntese , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Ácido Micofenólico/farmacologia , Bloqueadores dos Canais de Potássio , Canais de Potássio/fisiologia , Nucleotídeos de Purina/metabolismo , Ribonucleosídeos/farmacologiaRESUMO
Although mesenchymal stem cells (MSCs) are being tested for cardiac repair, the majority of transplanted cells undergo apoptosis in the ischaemic heart because of the effects of ischaemia/reperfusion, poor blood supply and other pro-apoptotic factors. Several experimental and clinical studies have suggested that cyclosporin A (CsA) treatment reduces apoptosis in human endothelial cells and neurocytes. However, the effect of CsA on the apoptosis in MSCs is still unclear. In this study, we investigated whether CsA could inhibit hypoxia/ reoxygenation (H/R)-induced apoptosis in MSCs. MSCs pre-incubated with or without CsA were subjected to 6 h of hypoxia followed by 12 h of reoxygenation. Our data showed that pre-incubation with 0.5-5 microM CsA dose-dependently protected the MSCs from H/R injury, as evidenced by decreased apoptosis and increased cell viability. CsA inhibited the H/R-induced translocation of cytochrome c, increased bcl-2 expression and restored mitochondrial membrane potential. CsA also increased the expression of p-BAD. We propose that preincubation MSCs with CsA inhibits MSC apoptosis through the mitochondrial and BAD pathway.