•Dietary interventions, including the Ketogenic Diet (KD), are recognized as powerful tools for treating and preventing diseases.•The KD's success has sparked optimism, making it a beacon of hope for ...individuals battling multiple symptoms associated with neurological diseases.•KDs may reduce neurodegeneration and inflammation by improving gut microbiota imbalances.•The KD offers non-pharmacological options for managing and preventing cardiovascular disease, particularly heart failure.
The Ketogenic Diet (KD) is a dietary regimen that is low in carbohydrates, high in fats, and contains adequate protein. It is designed to mimic the metabolic state of fasting. This diet triggers the production of ketone bodies through a process known as ketosis. The primary objective of KD is to induce and sustain ketosis, which has been associated with numerous health benefits. Recent research has uncovered promising therapeutic potential for KD in the treatment of various diseases. This includes evidence of its effectiveness as a dietary strategy for managing intractable epilepsy, a form of epilepsy that is resistant to medication. We are currently assessing the efficacy and safety of KD through laboratory and clinical studies. This review focuses on the anti-inflammatory properties of the KD and its potential benefits for neurological disorders and the gut-brain axis. We also explore the existing literature on the potential effects of KD on cardiac health. Our aim is to provide a comprehensive overview of the current knowledge in these areas. Given the encouraging preliminary evidence of its therapeutic effects and the growing understanding of its mechanisms of action, randomized controlled trials are warranted to further explore the rationale behind the clinical use of KD. These trials will ultimately enhance our understanding of how KD functions and its potential benefits for various health conditions. We hope that our research will contribute to the body of knowledge in this field and provide valuable insights for future studies.
In the present study, we investigated the effects of N-homocysteine thiolactone (tHcy) modification on expressed and purified tau protein and the synthesized VQIVYK target peptide. The modified ...constructs were subjected to comprehensive validation using various methodologies, including mass spectrometry. Subsequently, in vivo, in vitro, and in silico characterizations were performed under both reducing and non-reducing conditions, as well as in the presence and absence of heparin as a cofactor. Our results unequivocally confirmed that under reducing conditions and in the presence of heparin, the modified constructs exhibited a greater propensity for aggregation. This enhanced aggregative behavior can be attributed to the disruption of lysine positive charges and the subsequent influence of hydrophobic and p-stacking intermolecular forces. Notably, the modified oligomeric species induced apoptosis in the SH-SY5Y cell line, and this effect was further exacerbated with longer incubation times and higher concentrations of the modifier. These observations suggest a potential mechanism involving reactive oxygen species (ROS). To gain a deeper understanding of the molecular mechanisms underlying the neurotoxic effects, further investigations are warranted. Elucidating these mechanisms will contribute to the development of more effective strategies to counteract aggregation and mitigate neurodegeneration.
Background: Chronic lymphocytic leukemia (CLL), a common neoplastic disease, is associated with the accumulation of B-lymphocytes in the hematopoietic organs. A main characteristic of CLL cells is ...the failure to undergo apoptosis, thus resulting in resistance to several chemotherapeutics. Doxorubicin (DOX), an anthracycline widely used for treating various neoplasms including CLL, induces apoptosis via several mechanisms. Despite this, CLL cells become resistant to DOX. A major protein known as B-cell lymphoma-2 (Bcl-2), known to exert direct anti-apoptotic effects on the cell, is reported to be overexpressed in CLL cells. Methods: We aimed to silence the Bcl-2 gene by siRNA. Mononuclear cells were isolated from the peripheral blood and bone marrow of eleven untreated CLL patients by Ficoll-Paque. To transfect cells, we used Lipofectamine. Bcl-2 expression was investigated using qRT-PCR. Next, we studied the effect of Bcl-2 silencing in combination with DOX treatment on the viability of cells by an MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Results: Bcl-2 expression was significantly suppressed in CLL cells following siRNA transfection via lipofectamine. Based on the results of MTT, the inhibition of Bcl-2 sensitized CLL cells to DOX treatment. Also, the effect of the treatment was time-dependent. Conclusion: These findings imply that combination therapy of CLL using anti-Bcl-2 siRNA and DOX can be considered a practical therapeutic approach that should be further evaluated in future studies.
Neurodegenerative disorders such as Alzheimer's and Parkinson's disease inflict economic and health burdens on societies. Alzheimer's disease (AD), the most prevalent form of dementia, is accompanied ...by progressive degradation of memory, decision-making, and judgment. Parkinson's disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and loss of balance. Extensive research has pinpointed inflammation as a cause of the onset and progression of both diseases. However, it has not been confirmed which one is more formidable in terms of inflammation.
To assess the extent of inflammation that is implicated in AD and PD and answer the question of which one is more inflammatory, serum levels of inflammatory biomarkers, including cytokines, chemokines, and prostaglandin E2 (PEG2), were measured in AD and PD patients as well as a healthy group.
Our results showed a significant increase in IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12p70, IP-10, MCP-1, PEG2, and TNF-α in AD and PD patients compared with the control. Interestingly, IFN-γ did not manifest any significant difference in AD or PD patients compared with the control.
As a hallmark of our results, it could be inferred that inflammation, as the underlying etiological cause, plays a more crucial role in PD compared with AD. Based on our results, it is proposed that anti-inflammatory remedies would be putatively more effective in PD rather than AD.
Aims
COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or ...manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell
®
syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of
Boswellia spp
., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell
®
syrup, on moderate COVID-19 patients along with the current standard of care treatment.
Methods
A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell
®
syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial.
Results
Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (
P
< 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (
P
< 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (
P
< 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (
P
< 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (
P
< 0.002). Additionally, a significant decrease in CRP, LDH, IL − 6 and TNF − α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant.
Conclusion
Overall, the treatment with Inflawell
®
resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines.
Trial registration
The trial has been registered in
https://www.irct.ir
with unique identifier: IRCT20170315033086N10 (
https://en.irct.ir/trial/51631
). IRCT is a primary registry in the WHO registry network (
https://www.who.int/clinical-trials-registry-platform/network/primary-registries
).
In the present study, we investigated the effects of N-homocysteine thiolactone (tHcy) modification on expressed and purified tau protein and the synthesized VQIVYK target peptide. The modified ...constructs were subjected to comprehensive validation using various methodologies, including mass spectrometry. Subsequently, in vivo, in vitro, and in silico characterizations were performed under both reducing and non-reducing conditions, as well as in the presence and absence of heparin as a cofactor. Our results unequivocally confirmed that under reducing conditions and in the presence of heparin, the modified constructs exhibited a greater propensity for aggregation. This enhanced aggregative behavior can be attributed to the disruption of lysine positive charges and the subsequent influence of hydrophobic and p-stacking intermolecular forces. Notably, the modified oligomeric species induced apoptosis in the SH-SY5Y cell line, and this effect was further exacerbated with longer incubation times and higher concentrations of the modifier. These observations suggest a potential mechanism involving reactive oxygen species (ROS). To gain a deeper understanding of the molecular mechanisms underlying the neurotoxic effects, further investigations are warranted. Elucidating these mechanisms will contribute to the development of more effective strategies to counteract aggregation and mitigate neurodegeneration.
•A group of Iranian neurologists with experience in the field of MS gathered to develop a practical consensus in diagnosis and management of PPMS.•In this consensus recommendation, the authors try to ...review how to diagnose PPMS correctly and give answers to important questions in this field in order to define a uniform treatment strategy.•This consensus recommendation is the conclusion of a discussion among expert clinician neurologists, who are involved in this field.
The purpose of this study was to examine effects of performing preoperative preparation program on children's anxiety.
This study was performed in Amirkola Pediatrics Hospital, Mazandaran. A ...randomized controlled trail was performed on 122 children (7-12 years of age) admitted for elective surgery during 15 months. The researcher randomly assigned eligible participants in to the experimental and control groups, after pre-test baseline measurement had been taken. Analyzing was performed through independent t-test and χ(2) test. P<0.005 was considered statistically significant. The experimental group received therapeutic play and the control group received routine preoperative information preparation.
The mean and standard deviation of the state anxiety scores of children in experimental and control groups before intervention were 35.52±6.99 and 34.98±6.78, after intervention 31.44±5.87 and 38.31±7.44 respectively. The state anxiety score was lower significantly in the experimental group prior to preoperative surgery than in the control group (P=0.000).
Performing preoperative program with using therapeutic play intervention is effective for preparing children before surgery and decreases their anxiety.
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