Does the long-term administration of proton pump inhibitors increase the risk of adverse cardiovascular outcomes? A ChatGPT powered umbrella review.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for the treatment of acid-related disorders. In the context of coronary artery disease (CAD), PPIs are commonly prescribed along with antiplatelet medications. In fact, the potential interaction between these two classes of medications has been subject to much debate. This review aimed to summarise the findings from systematic reviews and meta-analyses on the casual relationship between PPI use (alone) and major adverse cardiovascular events (MACE). Furthermore, the recent release of ChatGPT has provided reviewers with a powerful natural language processing tool. We therefore aimed to assess the utility of ChatGPT in the systematic review process. METHODS: A comprehensive search of PubMed was conducted to identify relevant systematic reviews and meta-analyses published up to March 2023. Two independent reviewers assessed the eligibility of the studies, extracted the data, and assessed the methodological quality using AMSTAR 2.0. The population of interest was adults that received the medications of interest (PPIs) for a minimum of three months, regardless of indication. Control groups were defined as placebo or active comparators. The outcomes of interest were described under the general term MACE, which include cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. There were no restrictions with regards to time, but we only included reports in English. A different group of independent reviewers simultaneously ran the same process using ChatGPT. The results were then compared with the human generated results. RESULTS: Seven systematic reviews and meta-analyses were included, involving a total of 46 randomised controlled trials and 33 observational studies. The studies examined the association between PPI use and MACE, including stroke, myocardial infarction, and all-cause mortality. The results of the individual studies were conflicting, with some showing a positive association between PPI use and MACE, some showing no association, and others showing mixed results. However, the majority of the studies that included observational data reported a positive association between PPI use and MACE. Sensitivity analyses conducted in some studies did not significantly alter the primary results, suggesting that the findings were robust. Furthermore, ChatGPT was successfully prompted to execute most tasks involved in this review. We therefore present text that was generated by ChatGPT, including the abstract, introduction, results, and discussion sections. CONCLUSION: The findings of this umbrella review suggest that a causal relationship between PPI use and an increased risk of MACE cannot be ruled out. Further research is needed to better understand this relationship, particularly the underlying mechanisms and potential confounding factors. Healthcare professionals should consider the long-term use of PPIs and carefully weigh the risks and benefits for each patient. Finally, ChatGPT was successfully prompted to execute most of the tasks involved in this review. We therefore feel that this tool will be of great assistance in the field of evidence synthesis in the near future.

Protective Mechanisms of 3-Acetyl-11-keto-ß-Boswellic Acid and Piperine in Fluid Percussion Rat Model of Traumatic Brain Injury Targeting Nrf2 and NFkB Signaling.

The current study aimed to investigate the neuroprotective effect of 3-acetyl-11-keto-ß-boswellic acid (AKBA) in combination with bioenhancer piperine in lateral fluid percussion injury-induced TBI in experimental rats. Fluid percussion injury was introduced in the rat brain by delivering 50 mmHg of pressure for 3 min to the exposed brain. AKBA 25 mg/kg, 50 mg/kg orally, and AKBA (25 mg/kg, p.o.) in combination with piperine (2.5 mg/kg, p.o.) were administered from day 1 to day 14 to the assigned groups. On the 1st, 7th, and 14th day, behavioral parameters were checked. On the 15th day, animals were euthanized. In TBI rat model, AKBA-piperine combination significantly restored the altered performance of grip strength, rotarod test, open field task, narrow beam task (beam crossing time and no. of foot slips), and Morris water maze (escape latency and time spent in target quadrant) (p < 0.001 vs TBI control). Furthermore, the AKBA-piperine combination significantly reduced pro-inflammatory cytokine level in TBI rat model (&p < 0.001 vs TBI control). The combined effect of AKBA and piperine significantly restored oxidative stress parameters level, catecholamines level, and neurotransmitters level (p < 0.001 vs TBI control). Further findings showed that the AKBA-piperine combination prevented histopathological changes (p < 0.001), and the immunohistological study confirmed increased Nrf2-positive cells (p < 0.001 vs TBI control) and reduced nuclear factor kappa B (NFkB) expression (p < 0.001 vs TBI control, p < 0.01 vs TBI + AKBA 50 mg/kg) in the cortical region following AKBA-piperine administration. The present study concluded that AKBA along with piperine achieved anti-oxidant, and anti-inflammatory effects, and also prevented neuronal injury via targeting Nrf2 and NFkB expressions.

What Happens in TBI? A Wide Talk on Animal Models and Future Perspective.

Traumatic brain injury (TBI) is a global healthcare concern and a leading cause of death. The most common causes of TBI include road accidents, sports injuries, violence in warzones, and falls. TBI induces neuronal cell death independent of age, gender, and genetic background. TBI survivor patients often experience long-term behavioral changes like cognitive and emotional changes. TBI affects social activity, reducing the quality and duration of life. Over the last 40 years, several rodent models have been developed to mimic different clinical outcomes of human TBI for a better understanding of pathophysiology and to check the efficacy of drugs used for TBI. However, promising neuroprotective approaches that have been used preclinically have been found to be less beneficial in clinical trials. So, there is an urgent need to find a suitable animal model for establishing a new therapeutic intervention useful for TBI. In this review, we have demonstrated the etiology of TBI and post- TBI social life alteration, and also discussed various preclinical TBI models of rodents, zebrafish, and drosophila.

Understanding the Role of Histone Deacetylase and their Inhibitors in Neurodegenerative Disorders: Current Targets and Future Perspective.

Neurodegenerative diseases are a group of pathological conditions that cause motor incordination (jerking movements), cognitive and memory impairments result from degeneration of neurons in a specific area of the brain. Oxidative stress, mitochondrial dysfunction, excitotoxicity, neuroinflammation, neurochemical imbalance and histone deacetylase enzymes (HDAC) are known to play a crucial role in neurodegeneration. HDAC is classified into four categories (class I, II, III and class IV) depending upon their location and functions. HDAC1 and 2 are involved in neurodegeneration, while HDAC3-11 and class III HDACs are beneficial as neuroprotective. HDACs are localized in different parts of the brain- HDAC1 (hippocampus and cortex), HDAC2 (nucleus), HDAC3, 4, 5, 7 and 9 (nucleus and cytoplasm), HDAC6 & HDAC7 (cytoplasm) and HDAC11 (Nucleus, cornus ammonis 1 and spinal cord). In pathological conditions, HDAC up-regulates glutamate, phosphorylation of tau, and glial fibrillary acidic proteins while down-regulating BDNF, Heat shock protein 70 and Gelsolin. Class III HDACs are divided into seven sub-classes (SIRT1-SIRT7). Sirtuins are localized in the different parts of the brain and neuron -Sirt1 (nucleus), Sirt2 (cortex, striatum, hippocampus and spinal cord), Sirt3 (mitochondria and cytoplasm), Sirt4, Sirt5 & Sirt6 (mitochondria), Sirt7 (nucleus) and Sirt8 (nucleolus). SIRTs (1, 3, 4, and 6) are involved in neuronal survival, proliferation and modulating stress response, and SIRT2 is associated with Parkinsonism, Huntington's disease and Alzheimer's disease, whereas SIRT6 is only associated with Alzheimer's disease. In this critical review, we have discussed the mechanisms and therapeutic targets of HDACs that would be beneficial for the management of neurodegenerative disorders.