Enhancing the Anti-Leukemic Potential of Thymoquinone/Sulfobutylether-ß-cyclodextrin (SBE-ß-CD) Inclusion Complexes.

Leukemia, a condition characterized by the abnormal proliferation of blood cells, poses significant challenges in cancer treatment. Thymoquinone (TQ), a bioactive compound derived from black seed, has demonstrated anticancer properties, including telomerase inhibition and the induction of apoptosis. However, TQ's poor solubility and limited bioavailability hinder its clinical application. This study explored the use of Sulfobutylether-ß-cyclodextrin (SBE-ß-CD), a cyclodextrin derivative, to enhance the solubility and stability of TQ for leukemia treatment. SBE-ß-CD offers low hemolytic activity and has been successfully employed in controlled drug release systems. The study investigated the formation of inclusion complexes between TQ and SBE-ß-CD and evaluated their effects on leukemia cell growth and telomerase activity. The results indicated that the TQ/SBE-ß-CD complex exhibited improved solubility and enhanced cytotoxic effects against K-562 leukemia cells compared to TQ alone, suggesting the potential of SBE-ß-CD as a drug delivery system for TQ. The annexin V-FITC assay demonstrated increased apoptosis, while the qPCR quantification assay revealed reduced telomerase activity in leukemia cells treated with TQ/SBE-ß-CD, supporting its anti-leukemic potential. The molecular docking analysis indicated a strong binding affinity between TQ and telomerase. However, further research is needed to optimize the apoptotic effects and minimize necrosis induction. In conclusion, TQ/SBE-ß-CD shows promise as a novel strategy for leukemia treatment by inhibiting telomerase and enhancing the cytotoxic effects of TQ, offering a potential solution to overcome the limitations of TQ's poor solubility and bioavailability.

Characterization of Thymoquinone-Sulfobutylether-ß-Cyclodextrin Inclusion Complex for Anticancer Applications.

Thymoquinone (TQ) is a quinone derived from the black seed Nigella sativa and has been extensively studied in pharmaceutical and nutraceutical research due to its therapeutic potential and pharmacological properties. Although the chemopreventive and potential anticancer effects of TQ have been reported, its limited solubility and poor delivery remain the major limitations. In this study, we aimed to characterize the inclusion complexes of TQ with Sulfobutylether-ß-cyclodextrin (SBE-ß-CD) at four different temperatures (293-318 K). Additionally, we compared the antiproliferative activity of TQ alone to TQ complexed with SBE-ß-CD on six different cancer cell lines, including colon, breast, and liver cancer cells (HCT-116, HT-29, MDA-MB-231, MCF-7, SK-BR-3, and HepG2), using an MTT assay. We calculated the thermodynamic parameters (ΔH, ΔS, and ΔG) using the van't Holf equation. The inclusion complexes were characterized by X-ray diffraction (XRD), Fourier transforms infrared (FT-IR), and molecular dynamics using the PM6 model. Our findings revealed that the solubility of TQ was improved by ≥60 folds, allowing TQ to penetrate completely into the cavity of SBE-ß-CD. The IC50 values of TQ/SBE-ß-CD ranged from 0.1 ± 0.01 µg/mL against SK-BR-3 human breast cancer cells to 1.2 ± 0.16 µg/mL against HCT-116 human colorectal cancer cells, depending on the cell line. In comparison, the IC50 values of TQ alone ranged from 0.2 ± 0.01 µg/mL to 4.7 ± 0.21 µg/mL. Overall, our results suggest that SBE-ß-CD can enhance the anticancer effect of TQ by increasing its solubility and bioavailability and cellular uptake. However, further studies are necessary to fully understand the underlying mechanisms and potential side effects of using SBE-ß-CD as a drug delivery system for TQ.

Chloroquine and Hydroxychloroquine for the Prevention and Treatment of COVID-19: A Fiction, Hope or Hype? An Updated Review.

In December 2019, the novel coronavirus disease pandemic (COVID-19) that began in China had infected so far more than 109,217,366 million individuals worldwide and accounted for more than 2,413,912 fatalities. With the dawn of this novel coronavirus (SARS-CoV-2), there was a requirement to select potential therapies that might effectively kill the virus, accelerate the recovery, or decrease the case fatality rate. Besides the currently available antiviral medications for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), the chloroquine/hydroxychloroquine (CQ/HCQ) regimen with or without azithromycin has been repurposed in China and was recommended by the National Health Commission, China in mid-February 2020. By this time, the selection of this regimen was based on its efficacy against the previous SARS-CoV-1 virus and its potential to inhibit viral replication of the SARS-CoV-2 in vitro. There was a shortage of robust clinical proof about the effectiveness of this regimen against the novel SARS-CoV-2. Therefore, extensive research effort has been made by several researchers worldwide to investigate whether this regimen is safe and effective for the management of COVID-19. In this review, we provided a comprehensive overview of the CQ/HCQ regimen, summarizing data from in vitro studies and clinical trials for the protection against or the treatment of SARS-CoV-2. Despite the initial promising results from the in vitro studies and the widespread use of CQ/HCQ in clinical settings during the 1st wave of COVID-19, current data from well-designed randomized controlled trials showed no evidence of benefit from CQ/HCQ supplementation for the treatment or prophylaxis against SARS-CoV-2 infection. Particularly, the two largest randomized controlled trials to date (RECOVERY and WHO SOLIDARITY trials), both confirmed that CQ/HCQ regimen does not provide any clinical benefit for COVID-19 patients. Therefore, we do not recommend the use of this regimen in COVID-19 patients outside the context of clinical trials.

Prevalence and Association of Transfusion Transmitted Infections with ABO and Rh Blood Groups among Blood Donors at the National Blood Bank, Amman, Jordan.

Blood screening is considered a compulsory procedure in health care services to reduce the occurrence of transfusion transmitted infections (TTIs). This study estimated the distribution rates of ABO and Rh blood group systems, prevalence rates of TTIs among blood donors and their association with the ABO blood group and Rh system. A retrospective study was conducted at the national blood bank, Amman, Jordan for a period of 6 years (from January 2013 to December 2018). For TTIs analysis, about 5 mL blood sample was collected from each volunteer. A total of 365,029 persons (346,048 (94.8%) males and 18,981 (5.2%) females) donated their blood at the national blood bank, Amman, Jordan from January 2013 to December 2018. The results revealed that O and A were the most prevalent blood groups (37.44% and 36.82%, respectively), followed by B (18.62%) and AB (7.12%). The distribution of Rh + ve and Rh - ve among blood donors showed that Rh + ve donors were more prevalent (88.73%) compared with Rh - ve (11.27%). HBsAg was the most prevalent viral infection (0.38%) followed by HCV (0.13%), syphilis (0.02%), HIV (0.006%) and the male donors were highly infected when compared with female donors. The association between ABO/Rh blood groups and TTIs infections was nonsignificant. In conclusion, low frequency rates of TTIs among blood donors were detected in the current study, but improvements are still continuously required. Low percentages of female donors need to be managed via conducting health cultural education programs.

COVID-19 in Human, Animal, and Environment: A Review.

The medical authority in China, especially in Wuhan city, reported on December 2019 a large number of highly fatal, rapidly spreading viral pneumonia caused by an unknown coronavirus. The common history of all the patients was their visiting a Wuhan's whole food store, where live animals and seafood are sold. Irrespective of the efforts of the Chinese authorities, the virus spread rapidly all over the world by travelers, provoking widespread attention by the media and panic. Many previous coronavirus epidemics had been recorded, such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and the recently newly discovered epidemic is named coronavirus disease of 2019 (COVID-19). This disease is caused by SARS Coronavirus-2 (SARS-CoV-2), and this virus is antigenically related to the SARS virus (SARS-CoV), which had been detected in 2002, depending on clinical, serological, and molecular findings. There is rapid competition among the researchers to discover the source of the virus, understand the mechanism of the disease development, establish treatment strategies, and determine the factors affecting the incidence of infection and severity of the disease, and focus on the production of a vaccine. Coronaviruses are a group of single-stranded, positive-sense RNA genome viruses; its genome length varies from 26 to 32 kb. Coronavirus causes mild to severe respiratory disorders. In December 2019, several cases of pneumonia of unknown causes were found in Wuhan city, which is located in the Hubei province in China. Chinese health authorities investigated the problem and found that a new virus caused such infection and, using next-generation sequencing, found the 2019 novel coronavirus (2019-nCoV). It has been transferred from humans to humans and animals to humans (zoonotic). Coronaviruses cause multiple respiratory problems, varying from common cold to severe infections such as SARS. General symptoms of infection include fatigue, cough, and breathing problems such as shortness of breath, as described by World Health Organization. Serious cases may result in pneumonia, renal failure, and even death. We address current information about the new SARS Coronavirus-2 as well as the COVID-19 disease caused by it in this review.

Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats.

Acute kidney injury (AKI) is a serious complication of methotrexate (MTX). This study explored the protective effect of the isoflavone formononetin (FN) against MTX nephrotoxicity with an emphasis on oxidative stress, inflammation, and nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) signaling. Rats received FN (10, 20, and 40 mg/kg) for 10 days and a single dose of MTX on day 7. MTX induced kidney injury was characterized by increased serum creatinine and urea, kidney injury molecule-1 (Kim-1), and several histological alterations. FN ameliorated kidney function and inhibited the renal tissue injury induced by MTX. Reactive oxygen species (ROS), lipid peroxidation (LPO), nitric oxide, and 8-Oxo-2'-deoxyguanosine were increased, whereas antioxidant defenses were diminished in the kidney of MTX-administered rats. In addition, MTX upregulated renal iNOS, COX-2, TNF-α, IL-1ß, Bax, caspase-9, and caspase-3, and decreased Bcl-2, Nrf2, and HO-1. FN suppressed oxidative stress, LPO, DNA damage, iNOS, COX-2, proinflammatory cytokines, and apoptosis, and boosted Bcl-2, antioxidants, and Nrf2/HO-1 signaling in MTX-administered rats. In conclusion, FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation. Thus, FN may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity.

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

Side effects of anabolic steroids used by athletes at Unaizah Gyms, Saudi Arabia: a pilot study.

BACKGROUND: A large number of Saudi athletes are recently shown to use androgenic anabolic steroid (AAS) products to achieve rapid muscle growth without realizing the serious health risks of these drugs. Aim of this study was to elucidate the side effects encountered with prolonged use of AAS products by Saudi athletes. METHODS: A cross-sectional study was conducted, in which 16 regular gym members, 12 of them used AAS, were asked to answer a questionnaire and provide blood samples following current AAS course completion. Hemoglobin, serum proteins, lipid profile and hematological parameters were measured. Meanwhile, the parameters of kidneys, liver, heart, and immune system function were monitored. RESULTS: The subjects reported taking a 3-month course of an AAS comprising three compounds (testosterone enanthate, nandrolone decanoate and methandienone). A two-week gap separated every two courses, during which tamoxifen citrate (40 mg per day) and clomiphene citrate (10 mg per day) were taken to control serum testosterone levels. The intake of AAS one course had remarkable effects on some parameters related to kidney function. However, AAS three courses or more treatments showed abnormal liver and heart enzymes. Moreover, endogenous testosterone levels decreased dramatically with prolonged use of AAS (more than 10 courses). Alpha 2 protein increased by taking more than 10 courses, which might cause acute phase reactant of liver infection or inflammation. CONCLUSIONS: AAS products must be controlled by Saudi ministry of health and should not be taken randomly without the supervision of the healthcare professional.

Proteomic effects of wet cupping (Al-hijamah).

Wet cupping (Al-hijamah) is a therapeutic technique practiced worldwide as a part of the Unani system of medicine. It involves bloodletting from acupoints on a patient's skin to produce a therapeutic outcome. A thorough review of research articles on wet cupping with relevance to proteomics field that are indexed by Google Scholar, PubMed, and/or Science Direct databases was performed. Eight original research articles were summarized in this paper. Overall, wet cupping did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid exchanges, and cell replication index. In contrast, wet cupping was found to produce higher oxygen saturation, eliminate lactate from subcutaneous tissues, remove blood containing higher levels of malondialdehyde and nitric oxide, and produce higher activity of myeloperoxidase. The proteomic effects of wet cupping therapy have not been adequately investigated. Thus, future studies on wet cupping that use systemic and sound protocols to avoid bias should be conducted.