Honey targets ribosome biogenesis process in human pancreatic cancer cells to inhibit their growth and metastatic phenotypes

Background: Pancreatic cancer (PanCa) is the fourth deadliest cancer worldwide and is expected to become the second deadliest cancer by 2030. In the USA, the National Cancer Institute put forth a grim prediction stating that there will be 64,050 new cases in 2023 alone and about 50,000 of these patients will die. Existing therapeutic regimens against PanCa are not that effective and show unacceptable toxicities. Therefore, developing highly effective new agents with less toxicity is urgently required, which could be used as a monotherapy or as an adjuvant to treat PanCa patients. Honey is known for its tremendous health benefits and has been used in various traditional medicines. Several studies have defined honey to be cardioprotective, neuroprotective, ant-inflammatory, and immunomodulatory. In addition to these advantages, honey also possesses anti-cancer properties. However, no study has explored its effect against PanCa. In this study, we evaluated the anti-cancer potential of honey and its molecular mechanisms against PanCa. Methods: MTT assay and colony formation assays were performed to determine the effect of honey on proliferation of human PanCa cells (AsPc-1 and MiaPaCa-2). Wound healing assay was performed to evaluate the antimigratory potential of honey against PanCa cells. Western blot and qPCR assays were performed to determine the effect of honey on the regulation of ribosome biogenesis, cell proliferation, and apoptosis in PanCa cells. Results: Ribosome biogenesis is dysregulated in most cancer types, which results in aggressive metastatic phenotypes seen in cancer cells. We observed that the transcription factor UBTF and other ribosome biogenesis components were aberrantly overexpressed in pancreatic tumor tissues as compared to normal pancreatic tissues. These associations are linked to aggressive phenotypes seen in PanCa cells. Interestingly, we observed that honey treatment significantly suppressed ribosome biogenesis in PanCa cells as observed by significant decrease in UBTF and 5’-ETS expression. Honey treatment markedly inhibited the expression of RPA194, a catalytic unit of RNA polymerase I, and nucleolin in both AsPC-1 and MiaPaCa-2 cells. MTT analysis indicated that honey exerted dose-dependent cellular cytotoxicity in AsPc-1 and MiaPaCa-2 cells, with IC50 values 45.2 and 30.3 mg/ml, respectively. In addition to its potential cytotoxicity, honey treatment clearly interfered with the wound healing and clonogenic ability of these PanCa cells as demonstrated by wound healing and colony formation assays. We also observed that honey treatment induced apoptosis in AsPC-1 and MiaPaCa-2 cells, which was confirmed by the the increase of the population of Annexin V positive cells and cleavage of PARP protein. A decrease in expression of Bcl-2 and p53 (truncated in AsPc-1 and mutated in MiaPaCa-2) also indicated that these cancer cells were undergoing apoptosis. Conclusions: Overall, our results demonstrated for the first time that honey has potential to induce apoptosis and prevent pancreatic cancer cell growth through modulation of ribosome biogenesis process. It implies that honey could be used as a natural remedy to prevent human pancreatic cancer and utilized as an adjuvant in ongoing chemo/-immunotherapy regimens. Further detailed studies using appropriate pre-clinical mouse models of PanCa will be warranted to establish its anti-cancer potential for the treatment of PanCa

Incast mitigation in a data center storage cluster through a dynamic fair-share buffer policy

Incast is a phenomenon when multiple devices interact with only one device at a given time. Multiple storage senders overflow either the switch buffer or the single-receiver memory. This pattern causes all concurrent-senders to stop and wait for buffer/memory availability, and leads to a packet loss and retransmission—resulting in a huge latency. We present a software-defined technique tackling the many-to-one communication pattern—Incast—in a data center storage cluster. Our proposed method decouples the default TCP windowing mechanism from all storage servers, and delegates it to the software-defined storage controller. The proposed method removes the TCP saw-tooth behavior, provides a global flow awareness, and implements the dynamic fair-share buffer policy for end-to-end I/O path. It considers all I/O stages (applications, device drivers, NICs, switches/routers, file systems, I/O schedulers, main memory, and physical disks) while achieving the maximum I/O throughput. The policy, which is part of the proposed method, allocates fair-share bandwidth utilization for all storage servers. Priority queues are incorporated to handle the most important data flows. In addition, the proposed method provides better manageability and maintainability compared with traditional storage networks, where data plane and control plane reside in the same device

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.Peer reviewe

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Is Ozone therapy efficacious in the setting of Intervertebral disc pathologies? Protocol for systematic review & meta-analysis

IVD pathologies are being explored. Specifically, we shall be looking into whether there is definitive statistical proof that Ozone therapy is efficacious for IVD pathologies

Outcomes of Trabectedin for meningioma patients : Protocol of systematic review and meta analysis of RCTs

Meningioma is being studied. Specifically, we shall be looking into the outcomes of trabectedin for meningioma patients

Prediction of Glasgow Outcome Scale after Barbiturate Coma Therapy in patients suffering from Refractory Intracranial Hypertension after Brain Tumour Surgery: Incorporating Ensemble approach into automated Machine Learning

Ensemble approach is incorporated into Automated machine learning to predict Glasgow outcome scale and In-hospital mortality in patients receiving Barbiturate coma therapy for refractory intracranial hypertension post Brain tumour surgery

Predicting Alzheimer's disease from Clinical Dementia Rating, Estimated total intracranial volume & Atlas Scaling Factor : Incorporating Ensemble approach into Automated Machine Learning

The current state-of-the-art for automated machine learning is adopted to predict Alzheimer's disease (AD) by adopting variables such as Mini Mental State Examination score, estimated total intracranial volume and Atlas Scaling Factor. A macro-weighted average Area under the Response-operating Curve of 0.96 is achieved with a close-to-perfect AD detection score after incorporating the ensemble approach. Such predictive models shall serve to optimize risk stratification and management protocols for this enfeebling ailment

Prediction of Overall survival and Progression-free survival for Glioblastoma Multiforme treated with a moderately escalated radiation dose - Amalgamating Ensembled approach into Automated Machine Learning

Automated machine learning is adopted to develop prognostication models for overall survival and progression-free survival after a patient suffering from glioblastoma undertakes adjuvant escalated radiotherapy