A randomized, double-blind placebo-controlled phase I clinical study on safety and efficacy of the G-Rup® syrup (a mixture of ginger extract and honey) in symptomatic treatment of knee osteoarthritis.

WHAT IS KNOWN AND OBJECTIVES: Present study evaluated the safety profile and efficacy of G-Rup® syrup (100 mg/ml ginger extract plus 150 mg/ml honey) in symptomatic treatment of knee osteoarthritis (OA). METHODS: Patients diagnosed with knee OA were randomly assigned (1:1) to receive either of a 30 ml twice daily regimen of G-Rup® syrup or placebo over a 12-week period. Primary endpoints of the study comprised of an improvement in the joint's stiffness, physical functioning and pain score, assessed by WOMAC questionnaire and the visual analog scale (VAS). Secondary objectives comprised of safety and tolerability of the syrup by patients. RESULTS AND DISCUSSION: The 30 ml twice-daily regimen of G-Rup® syrup was safe and well tolerated by patients. Moreover, in whole studied time points, treatment with G-Rup® syrup could significantly Power the VAS score (p < 0.001) whereas improving WOMAC total score (p < 0.001) and pain (p < 0.001), physical functioning (p < 0.001), and stiffness sub-scores (p = 0.006) compared to the placebo receiving group. WHAT IS NEW AND CONCLUSION: Based on obtained results, the G-Rup® syrup, composed of a combination of honey and ginger, may be a proper supplementary choice, along with routine therapeutic regimens, for improvement of symptomatic treatment of OA.

Cyclopentadienones via a tandem C-cyclopropylnitrone cyclization-cycloreversion sequence.

Aldonitrones derived from spiro[2.4]hepta-4,6-diene-1-carbaldehyde and its benzo analog undergo a tandem uncatalyzed intramolecular cyclopropane-nitrone cyclization-5,6-dihydro-1,2-oxazine cycloreversion to give cyclopentadienones. Similarly, the NH-nitrone generated in situ from spiro[cyclopropane-1,1'-indene]carbaldehyde oxime leads to benzocyclopentadienone (1H-inden-1-one) by the same mechanism. DFT calculations are in favor of a concerted yet highly asynchronous pathway for the cyclizations. Control experiments with the dihydro and tetrahydro derivatives show that the spirocyclopentadiene unit is essential for the success of the reaction, invoking spiroconjugative effects for increased cyclopropane reactivity.

Efficacy and Safety of a DOAC Compared to Unfractionated Heparin and A Low Molecular Weight Heparin in the Prevention of Thromboembolism in Hematopoietic Stem Cell Transplant Recipients.

Background: Hematopoietic stem cell transplantation (HSCT) patients are at risk of thromboembolic events, making thromboprophylaxis crucial. Objectives: This study aimed to compare apixaban, a direct factor Xa inhibitor (DOAC), with dalteparin and unfractionated heparin for thromboprophylaxis in HSCT recipients. The safety outcome included the assessment of hemorrhagic events. Methods: In this open-label randomized clinical trial, 182 HSCT recipients were divided into three groups: Apixaban (n = 61, 2.5 mg two times a day), dalteparin (n = 59, 5000 IU daily), and unfractionated heparin (n = 62, 5000 IU twice daily). These anticoagulant regimens were administered after central vein catheterization and during hospitalization. The primary clinical outcome was the risk of thrombosis, and the secondary outcome was the rate of bleeding. Relevant laboratory results were analyzed using appropriate statistical tests. Results: Among the 61 patients in the apixaban group, six experienced thrombosis (9.83%), with four (6.65%) of them on anticoagulants. In the dalteparin group, three patients (5%) developed thrombosis, two of whom (3.38%) were on anticoagulants. In the heparin group, all four thrombosis cases (6.4%) occurred in patients on anticoagulants (P = 0.543 overall and P = 0.776 in anticoagulant users). Only two cases of bleeding were reported (1.09% overall), one in the dalteparin group (1.69%) and the other in the apixaban group (1.63%). Conclusions: Apixaban, dalteparin, and heparin demonstrated similar effectiveness in preventing thromboembolism in HSCT recipients. Furthermore, the comparison of bleeding rates across the study groups did not reveal significant differences. Larger studies with higher event rates may yield more precise conclusions.

Temperature-dependent, competitive 1,3-acyl shift versus decarbonylation of a cyclopropanone intermediate.

Photooxygenation of 1,1,3-trimethyl-1,2-dihydropentalene gives an unstable endoperoxide which upon decomposition delivers a bicyclic cyclopropanone intermediate; this species either extrudes CO to give a cycloheptadienone or undergoes a 1,3-acyl shift, both processes occurring most likely in a stepwise manner via diradical intermediates. Alternatively, C3a-C4 cleavage in the dioxygen diradical derived from the endoperoxide yields a 2-cyclopropyl substituted cyclopentadienone epoxide.

Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. METHODS: We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. RESULTS: Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I 2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I 2 = 26.798%, P-value = 0.242). CONCLUSION: CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.

Pharmacological Interventions for the Prevention and Treatment of Kidney Injury Induced by Radiotherapy: Molecular Mechanisms and Clinical Perspectives.

More than half of cancer patients need radiotherapy during the course of their treatment. Despite the beneficial aspects, the destructive effects of radiation beams on normal tissues lead to oxidative stress, inflammation, and cell injury. Kidneys are affected during radiotherapy of abdominal malignancies. Radiation nephropathy eventually leads to the release of factors triggering systemic inflammation. Currently, there is no proven prophylactic or therapeutic intervention for the management of radiation-induced nephropathy. This article reviews the biomarkers involved in the pathophysiology of radiation-induced nephropathy and its underlying molecular mechanisms. The efficacy of compounds with potential radioprotective properties on amelioration of inflammation and oxidative stress is also discussed. By outlining the approaches for preventing and treating this critical side effect, we evaluate the potential treatment of radiation-induced nephropathy. Available preclinical and clinical studies on these compounds are also scrutinized.

COVID-19-infected woman along with tuberculosis and psychogenic non-epileptic seizures: A case report.

During the COVID-19 pandemic, we should not forget about chronic, underlying and important diseases, especially diseases that cause immune system deficiency, of which TB is one and may be missed. Also, we should pay attention to the past medical history of the patients and their drug-drug interactions during the treatment period of COVID-19. Our main clinical message is that diseases such as TB, which weaken the immune system, may predispose a person to COVID-19 infection and COVID-19 may exacerbate TB and it's mortality. On the other hand, diseases that target the lung tissue such as TB and COVID-19, may have synergistic effects and increase mortality (for a patient whose lung capacity is reduced due to TB, superimposed COVID-19 can worsen the situation). In addition, it may be necessary to take more serious considerations for COVID-19 in low socio-economy countries, such as Afghanistan, where TB is more prevalent.

Aromatic hydrocarbon receptors in mitochondrial biogenesis and function.

Mitochondria are ubiquitous membrane-bound organelles that not only play a key role in maintaining cellular energy homeostasis and metabolism but also in signaling and apoptosis. Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors that recognize a wide variety of xenobiotics, including polyaromatic hydrocarbons and dioxins, and activate diverse detoxification pathways. These receptors are also activated by natural dietary compounds and endogenous metabolites. In addition, AhRs can modulate the expression of a diverse array of genes related to mitochondrial biogenesis and function. The aim of the present review is to analyze scientific data available on the AhR signaling pathway and its interaction with the intracellular signaling pathways involved in mitochondrial functions, especially those related to cell cycle progression and apoptosis. Various evidence have reported the crosstalk between the AhR signaling pathway and the nuclear factor κB (NF-κB), tyrosine kinase receptor signaling and mitogen-activated protein kinases (MAPKs). The AhR signaling pathway seems to promote cell cycle progression in the absence of exogenous ligands, whereas the presence of exogenous ligands induces cell cycle arrest. However, its effects on apoptosis are controversial since activation or overexpression of AhR has been observed to induce or inhibit apoptosis depending on the cell type. Regarding the mitochondria, although activation by endogenous ligands is related to mitochondrial dysfunction, the effects of endogenous ligands are not well understood but point towards antiapoptotic effects and inducers of mitochondrial biogenesis.

Large-scale association analysis of climate drought and decline in groundwater quantity using Gaussian process classification (case study: 609 study area of Iran).

BACKGROUND: The level of groundwater resources is changing rapidly and this requires the discovery of newer groundwater resources. Drought is one of the most significant natural phenomena affecting different aspects of human life and environment. During the last decades, the application of artificial intelligent techniques has been recognized as effective approaches to forecast an annual precipitation rate. METHOD: In this study, the association analysis of climate drought and a decline in groundwater level is addressed using Gaussian process classification (GPC) and backpropagation (BP) artificial neural network (ANN). This methodology is proposed to create a framework for decision making and reduce uncertainty in water resource management calculations, and in particular to optimize the management of groundwater drinking water sources. RESULTS: Underground water levels in 609 study plains in Iran were used to predict drought over the test period, extending from 2017 to 2021. The artificial intelligence methods were implemented in the Python programming environment to achieve an annual precipitation rate. A statistical summary of the Rasterized Cells of the zoning maps was used to validate the prediction results. Considering the relationship between water quality reductions and drought in Iranian aquifers due to the occurrence of groundwater drought periods, the results were validated by analysis of the effect of climate drought using the Standardized Precipitation Index (SPI) on the occurrence of observed droughts with the Groundwater Resources Index (GRI). The results are well-illustrated by the observation of the predicted digits in the third dimension of the Gaussian distribution. CONCLUSION: According to the SPI indicator, the southern regions of the country, and especially the central parts of the plain, can be considered the most affected areas by the most severe future droughts. The prediction results indicate a decrease in drought severity as part of a two-year sequence involving a recurrence of drought exacerbation and relative decline, as well as a failed state after the critical condition of aquifers.

1,2-Dihydropentalenes from fulvenes by [6 + 2] cycloadditions with 1-isopropenylpyrrolidine.

In situ generated acetone pyrrolidine enamine undergoes [6 + 2] cycloadditions with fulvenes to give 1,2-dihydropentalenes. This ring annulation method works particularly well with 6-monosubstituted fulvenes and is subject to steric hindrance at C-6 of the fulvene. On the basis of mechanistic studies, optimal conditions have been developed for a one-pot synthesis of 1,2-dihydropentalenes using catalytic amounts of pyrrolidine.