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Radioulnar synostosis (RUS) is a rare, congenital bone anomaly characterized by fusion of the radius and the ulna. RUS occurs more often in males than in females and is bilateral in 50% of the cases. More than 400 cases of RUS have been described since 1793. In the literature, seven cases with RUS and hematologic problems were reported, including the newly named radioulnar synostosis-hematology syndrome. Globally, this is the first reported case of RUS associated with malignancy, that is, acute lymphoblastic leukemia, in a 3-year-old male child.

The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the oral microbiota impact the state of sickle cell anemia. Using next-generation sequencing, the 16S rRNA amplicon was examined using saliva samples from 36 individuals with sickle cell anemia and healthy individuals. These samples were obtained from sickle cell anemia patients (18 samples) and healthy control participants (controls, 18 samples). Various analyses are conducted using bioinformatic techniques to identify distinct species and their relative abundance. Streptococcus , followed by Fusobacterium nucleatum , Prevotella , and Veillonella were the most prevalent genera of bacteria in the saliva of the SCA and non-SCA individuals according to our findings. Rothia mucilaginosa , Prevotella scoposa , and Veillonella dispar species were the dominant species in both sickle cell anemia and non-sickle cell anemia subjects. Streptococcus salivarius , Actinomyces graevenitzii , Actinomyces odontolyticus , and Actinomyces georgiae spp. were the most prevalent bacterial spp. in the studied SCA cases. The sequencing of the 16S rRNA gene yielded relative abundance values that were visualized through a heatmap analysis. Alterations in the oral microflora's constitution can significantly affect the susceptibility of sickle cell anemia patients to develop more severe health complications. Salivary diagnosis is a potential tool for predicting and preventing oral microbiome-related diseases in the future.

Background: It is well-established that specific herbal plants contain natural active ingredients that have demonstrated anti-cancer potential. Therefore, they are considered highly beneficial as a potential adjuvant, alternative or complementary agent in anti-cancer therapy. However, the low chemical stability and limited bioavailability of 3, 3'-Diindolylmethane (DIM), a plant-derived compound used in clinical settings, limit its therapeutic applications. To overcome this challenge, researchers have focused on developing innovative approaches to improve DIM's biological activity, such as utilizing nanoformulations. Here, we investigated the potential benefits of coating DIM nanoparticles (DIM-NPs) with PEG/chitosan in the treatment of breast cancer. Our results demonstrate the molecular mechanism underlying the activity of DIM-NPs, highlighting their potential as an effective therapeutic strategy for breast cancer treatment., Methods: DIM-PLGA-PEG/chitosan NPs were synthesised and characterised using dynamic light scattering (DLS) and evaluated the impact of these NPs on two breast cancer cell models., Results: DIM-NPs had an average diameter of 102.3 nm and a PDI of 0.182. When treated with DIM-NPs for 48 h, both MCF7 and MDA-MB-231 cells displayed cytotoxicity at a concentration of 6.25 g/mL compared to untreated cells. Furthermore, in MDA-MB-231 cells, treatment with 2.5 μg/mL of DIM-NPs resulted in a significant decrease in cell migration, propagation, and angiogenesis which was further enhanced at 10 μg/mL. In chicken embryos, treatment with 5 μg/mL of DIM-NPs on day 2 led to a significant reduction in angiogenesis. Furthermore, this treatment induced cell death through a regulatory pathway involving the upregulation of Bax and p53, as well as the downregulation of Bcl-2. These results were supported by in-silico analysis of DIM's binding affinity to key proteins involved in this pathway, namely Bax, Bcl-2, and p53., Conclusion: Our findings show that DIM-NPs induces apoptosis, inhibit migration, and reduce angiogenesis in breast cancer. However, further research using a preclinical cancer model may be necessary to determine the pharmacokinetics of DIM-NPs and ensure their safety and efficacy in vivo., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity., Methods: Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells., Results: The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL ( p  < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis ( p  < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells., Conclusion: Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

trans-Anethole a valuable compound derived from star anise widely used by ethnic tribals to manage numerous human diseases. In this study antiproliferative activities of trans-Anethole towards human liver cancer (HepG2), cervical cancer (HeLa) and breast cancer (MCF-7) cells were explored. trans-Anethole showed free radical scavenging potential as assessed by DNA nicking assay. trans-Anethole exhibited strong antiproliferative potential towards HepG2 cells compared to other cell lines. trans-Anethole strongly induced apoptosis in HepG2 cells by significantly upregulating the protein expressions of p53, Caspase-3 and Caspase-9 were assessed by western blotting analysis which highlighted apoptosis-inducing capacity of trans-Anethole against HepG2 cells. Rt-qPCR analysis revealed that trans- Anethole upregulated p53, caspase - 3 and - 9 in comparison to untreated HepG2 cancer cells. Moreover, trans-Anethole provoked the generation of ROS and disruption of MMP. Our research suggests that trans-Anethole may have a significant anticancer therapeutic potential for treating liver cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing for financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Olive tree (Olea europaea, Oleaceae) leaf extract (OLE) exerts many biological activities. One of the most common polycyclic aromatic hydrocarbons (PAHs) that pollute the environment is 2-amino-l-methyI-6-phenyI-imidazo pyridine (PhIP). It is a food-derived carcinogen that is present in fish and meat that has been cooked at high temperatures. Due to the generation of reactive electrophilic species, phase I enzymes have the potential to cause oxidative damage. In order to safely remove these reactive species from the body, phase II detoxification (conjugation) enzymes are necessary. It is not known whether OLE could influence their activities and hence reduce the carcinogenic effects of PhIP. This study evaluated whether OLE could modulate phase I detoxifying enzymes as well as phase II enzymes that metabolize PhIP in rat liver microsomes. Four groups of rats were used: group I: no treatment; group II: OLE (10 mg/kg bw orally); group III: PhIP (0.1 mg/kg bw orally); and group IV: PhIP followed by OLE. After 4 weeks, the activities of phase I enzymes such as CYP1A1 (ethoxyresorufin O-deethylase), CYP2E1 (p-nitrophenol hydroxylase), CYP1A2 (methoxyresorufin O-demethylase), UDP-glucuronyl transferase, sulphotransferase, and glutathione-S transferase were evaluated in rat liver microsomes. Analysis of OLE by gas chromatography-mass spectrometry (GC/MS) showed various active ingredients in OLE, including 3,5-Heptadienal (C10H14O), 3,4-dimethoxy benzoic acid (C8H10O3), 4-hydroxy-3-methoxy (C8H8O4), 1,3,5-Benzenetriol (C6H6O3), hexadecanoic acid (C16H32O2), and hexadecanoic acid ethyl ester (C18H36O2). Our results showed that rats given PhIP were found to have a statistically significant (p < 0.001) reduction in the activities of CYP1A1, CYP1A2, and CYP2E1 in comparison with the control group. However, treatment with OLE enhanced their activities but not to a normal level compared with untreated groups. Administration of PhIP decreased the activities of phase II enzymes (glutathione S-transferase, UDP-glucuronyltransferase, or sulphotransferase) (p < 0.01) in comparison with the control group. Histological examination of rat livers was consistent with the biochemical changes. The administration of OLE improved the phase II enzyme activities in animals injected with PhIP. We conclude that OLE influences phase I and phase II detoxification enzymes exposed to PhIP, which may represent a new approach to attenuating carcinogenesis induced by it., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Date was considered a high nutritional value fruit due to its high content of active ingredients. Frequent exposure to cosmetic radiations including UVC caused deleterious effects and tissue damage and organ affection. This study investigated the efficacy of Ajwa date extract (ADE) in protection against UVC-induced kidney injury in rats. Five groups of rats were included in this study. Group I: Rats were exposed to UVC radiation at a dose 5 kJ (1 h/day) for 28 days. Group II: Rats were pretreated orally with ADE (10 mg/kg/day) 1 h before exposure to UVC radiation with dose 5 kJ. Group III: Rats were pretreated with ADE (15 mg/kg) 1 h before exposure to UVC radiation. Group IV: Rats were exposed to UVC radiation then treated with ADE (10 mg/kg). Group V: Rats exposed to UV radiation then treated with ADE (15 mg/kg) after 1 h from exposure. Analyzing the active constituents of ADE by GC/MS showed that, quercetin, myricetin kaempferol, thymine, and catechol are the most active ingredients. Biochemical markers obtained showed that, serum 8-oxoguanine as marker for DNA damage was increased, and total antioxidant activity and glutathione reduced were decreased (p < 0.01), while neutrophil (p < 0.001), conjugated diene (p < 0.05), and interferon-γ (p < 0.01) were increased after exposure to UVC. However, all the parameters changed were reversed by ADE-treated rats compared with untreated; the higher dose was more effective and protective effect was better than treated effect. Kidney total proteins and reduced glutathione and procollagen levels were decreased while malondialdehyde was increased after exposure to UVC (p < 0.01). These abnormalities were normalized by ADE treatment and protected. It was concluded that, flavonoids from Ajwa extract protected against deleterious effects of UVC by enhancing antioxidant activities and reducing infiltration of neutrophils that caused kidney injury., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The obesity increased incidence of diabetes, hypertension and atherosclerosis and rate of morbidity and mortality. The main cause of atherosclerosis is endothelial dysfunction and formation of foam cells and macrophage that lead to unfavorable complications. This study evaluated specific biomarkers for endothelial dysfunction as sensitive indices for early predication of atherosclerosis in obese subjects., Study Design: One hundred fifty male age and sex matching were included in the current study divided into three groups according to body mass index (BMI): Control (BMI ≤ 22), obese (BMI> 28) and obese with atherosclerosis (BMI> 28). Fasting serum was subjected for determination of adhesion molecules, sICAM-1, sVCAM-1, E-selectin, oxo-LDL and 8-iso-PGF2α by ELISA technique., Results: Data obtained showed that, a significant elevation of serum inflammatory markers CRP, IL-6 and TNF-α and adhesion molecules sICAM-1 (p<0.001) with sensitivity 96%, sVCAM-1 (p <0.01) with sensitivity 92%, E-selectin (p<0.001) with sensitivity 94%, oxo-LDL (p <0.05) and 8-iso-PGF2α (p < 0.001) with sensitivity 97% in obese with atherosclerosis compared with obese and control., Conclusion: The levels of serum adhesion molecules contributed in the pathogenesis of endothelial dysfunction can be used as sensitive biomarkers for early prediction of atherosclerosis in obese subjects., (© 2022 Abulnaja KO et al.)

Background: Iron deficiency (ID) and ID anemia (IDA) are common in the member states of the Gulf Cooperation Council (GCC). The unique genetic and lifestyle factors of the patient population in the region have necessitated the development of recommendations to help educate health-care professionals on appropriate diagnosis and management of ID/IDA., Methods: A panel of regional experts, including gastroenterologists and hematologists with expertise in the treatment of IDA, was convened to develop regional practice recommendations for ID/IDA. After reviewing the regional and international literature, the expert panel developed consensus recommendations for screening, diagnosis, and treatment of patients with IDA in the GCC region., Results: The recommendations proposed were customized to the patient population keeping in view the increasingly recognized burden of coeliac disease, high fertility and obesity rates, high prevalence of alpha- and beta-thalassemia traits, and poor tolerance and low treatment compliance with oral iron therapy., Conclusions: This consensus statement proposes recommendations for screening, diagnosis, and treatment of IDA in the GCC region., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

This nonrandomized controlled trial determined the effects of Phoenix dactylifera palm date (Ajwa) intake on the number of infections and hospitalizations associated with fever, neutropenia, and mortality of pediatric cancer patients admitted between 2008 and 2017 to King Abdulaziz University Hospital (Jeddah, Saudi Arabia). Patients were eligible to be enrolled if they fulfilled the inclusion criteria, were not allergic to Ajwa, and were not enrolled in another study. Of 200 screened patients, 56 were included and 144 were excluded. Of the 56, 26 agreed to take Ajwa, and 30 served as controls. Both groups were assessed based on infection rates, frequency of hospital admissions for fever and neutropenia, and mortality rate. Background information regarding demographics, clinicopathological data, and treatment options was documented. Supplementation of Ajwa significantly reduced hospital admissions (for fever-associated neutropenia) and infections ( P = .009 and P < .001, respectively). Off-treatment did not significantly differ between the Ajwa and control groups. The Ajwa group had a better survival rate in comparison to the non-Ajwa group (stratified log-rank P = .005), where the main cause of death of patients in the non-Ajwa group was disease progression associated with infections (77%). In summary, Ajwa intake during the standard treatment of pediatric cancer patients improved their treatment outcome.

This in vitro pilot study was performed to determine whether a treatment algorithm including mechanical debridement, followed by air powder abrasion with glycine, followed by citric acid conditioning with vigorous flushing of the surface with sterile water after each step, is capable of decontaminating an infected implant surface. A total of 14 dental implants that were deemed hopeless due to advanced peri-implantitis were extracted. Of these, 6 implants served as tests and had their exposed surfaces treated with the decontamination protocol, 6 served as untreated controls, and 2 were mechanically treated only, followed by rubbing the surface with sterile saline. All implants were placed in culture with human osteoprogenitor cells for 72 hours, and evaluation was performed using scanning electron microscopy. The 6 test implants all demonstrated attachment and proliferation of the normal human osteoprogenitor cells on their prior exposed and decontaminated surfaces. All of the untreated control and the mechanically debrided, sterile water-treated implants failed to demonstrate this same success. The results suggest that this protocol can decontaminate an implant surface affected by peri-implantitis. Further studies are warranted to determine if this technique would demonstrate similar success over a greater number of implants and whether this outcome may occur in humans.

Honey exhibits antimicrobial activities against a wide range of bacteria in different milieu. This study aims to compare the effects of five types of honey (both imported and local Saudi honey) against Staphylococcus aureus . The five types of honey (Manuka Honey UMF +20, Manuka Honey UMF +16, Active +10 Manuka Honey, Sidr honey and Nigella sativa honey) were evaluated for their bactericidal/bacteriostatic activities against both methicillin resistant and sensitive S. aureus . The inhibitory effect of honey on bacterial growth was evident at concentrations of 20% and 10% (v/v). Manuka Honey showed the best results. Manuka Honey UMF +20 had a bactericidal effect on both methicillin resistant and sensitive S. aureus . However, Sidr and N. sativa honey exerted only a bacteriostatic effect. The efficacy of different types of honey against S. aureus was dependent on the type of honey and the concentration at which it was administered. Manuka Honey had the best bactericidal activity. Future experiments should be conducted to evaluate the effects of honey on bacterial resistance.

Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling. Studies are underway to investigate the potential role of selectin antagonists, for prevention and reversal of acute vascular occlusions in SCD patients.

Background: A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5 × 10(9)/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real-life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis., Procedure: This non-interventional surveillance program assessed the monitoring of deferiprone therapy in clinical practice. A total of 294 patients with transfusion-dependent anemias received deferiprone, as monotherapy or with another chelator, for up to 1 year. The participating physicians were not given any instructions about treatment and monitoring beyond being referred to the information in the package insert., Results: ANC monitoring was conducted at an average interval of 5 ± 4 weeks, and deferiprone was not always interrupted upon detection of neutropenia. One patient (0.3%) experienced agranulocytosis, and nine others (3%) experienced a total of 11 episodes of neutropenia. All neutropenia episodes resolved; median time to resolution was similar whether or not treatment was interrupted; and no case of neutropenia progressed to agranulocytosis., Conclusions: These data indicate that less frequent ANC monitoring and continuation of deferiprone therapy during neutropenia are not associated with prolonged neutropenia or with progression to agranulocytosis., (© 2014 Wiley Periodicals, Inc.)

Background. Besides lipid-lowering effect of statins, they have been shown to have nonlipid lowering effects, such as improving bone health. An improvement in bone mineral density (BMD) has been indicated in some studies after the use of statins, in addition to an increase in 25-hydroxyvitamin D (25OHD) level. The aim of this study is to explore the association between statins and bone health taking into consideration 25OHD level and BMD. Methods. This is a randomized, cross-sectional comparative study. Subjects were divided into two groups, hypercholesterolemic participants taking simvastatin or atorvastatin as the study group and a matched control group not taking statins. All participants were assessed for serum 25OHD and BMD at lumbar spine and femoral neck. Results. A total of 114 participants were included in the study, 57 participants in each group. Results of serum 25OHD showed no significant difference between study and control groups (P = 0.47), while BMD results of lumbar spine and femoral neck showed significant difference (P = 0.05 and 0.03, resp.). Conclusion. Simvastatin and atorvastatin, at any dose for duration of more than one year, have no additive effect on 25OHD level but have a positive effect on the BMD.

Sickle-cell disease (SCD) is a wide-spread inherited hemolytic anemia that is due to a point mutation, leading to the substitution of valine for glutamic acid, causing a spectrum of clinical manifestations in addition to hemolysis and anemia. Acute painful crisis is a common sequela that can cause significant morbidity and negatively impact the patient's quality of life. Remarkable improvements in the understanding of the pathogenesis of this clinical syndrome and the role of cell adhesion, inflammation, and coagulation in acute painful crisis have led to changes in the management of pain. Due to the endemic nature of SCD in various parts of the Middle East, a group of physicians and scientists from the United States and Middle East recently met to draw up a set of suggested guidelines for the management of acute painful crisis that are reflective of local and international experience. This review brings together a detailed etiology, the pathophysiology, and clinical presentation of SCD, including the differential diagnoses of pain associated with the disease, with evidence-based recommendations for pain management and the potential impact of low-molecular-weight heparin (LMWH), from the perspective of physicians and scientists with long-term experience in the management of a large number of patients with SCD.

Osteoporosis is a complicated and preventable disease with major morbidity complications that affects millions of people. In the last 15 years, there have been numerous studies and research in the new fields of pharmacogenetics and pharmacogenomics related to osteoporosis. Numerous "candidate genes" have been identified and have been found to be associated with osteoporosis as well as the treatment of osteoporosis. Many studies have found conflicting results on different polymorphisms and whether or not they are related to bone mineral density and osteoporosis. There is a need for larger and better designed pharmacogenomic studies related to osteoporosis incorporating a greater variety of candidate genes. The evaluation of osteoporosis and fracture risk is moving from a risk stratification approach to a more individualized approach, in which an individual's absolute risk of fracture is evaluable as a constellation of the individual's environmental exposure and genetic makeup. Therefore, the identification of gene variants associated with osteoporosis phenotypes or response to therapy might help individualize the prognosis, treatment, and prevention of fracture. This review focuses on major candidate genes and what needs to be done to take the genetics of osteoporosis and incorporate them into the pharmacogenomics of the management of osteoporosis.

Considerable progress has been made in the understanding of the risk factors for venous thromboembolism (VTE). The clinical applications of molecular techniques have allowed identification of important inherited, yet not uncommon, risk factors for VTE, such as mutations that cause Factor V Leiden and prothrombin G20210A. However, advances in our understanding have raised several questions regarding the need for, and duration of anticoagulation. At the end of the treatment period, low molecular weight heparins have become the drugs of choice and standard-of-care for VTE. In this review, cost effective diagnostic approaches for patients with suspected deep vein thrombosis, and recommended treatment options using evidence-based approaches, are described.

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Parvovirus B19 infection is common worldwide but is often asymptomatic. However, the virus has been implicated in numerous disorders, including aplastic crisis in patients with chronic hemolytic anemia, erythema infectiosum, arthropathy, arthritis, and fetal infections. Diagnostic tests are not routine, but several are available through commercial reference laboratories. Treatment ranges from analgesics and antipyretics for mild and self-limited illness to administration of commercial immunoglobulin preparations and blood transfusion for more serious conditions.