Inhibitory Potential of the Ocimum sanctum Phytochemicals on Bruton's Tyrosine Kinase, a Well-Known Drug Target for Treatment of Chronic Lymphocytic Leukemia: An In Silico Investigation.

Chronic lymphocytic leukemia (CLL) is an incurable neoplasm of B-lymphocytes, which accounts for about one-third of all leukemias. Ocimum sanctum, an herbaceous perennial, is considered as one of the important sources of drugs for the treatment of various diseases, including cancers and autoimmune diseases. The present study was designed to screen various phytochemicals of O. sanctum for discovering their potential to inhibit Bruton's tyrosine kinase (BTK), a well-known drug target of CLL. Various phytochemicals of O. sanctum were screened for their potential to inhibit BTK using several in silico protocols. First, the molecular docking approach was used to calculate the docking scores of the selected phytochemicals. Then, the selected top-ranked phytochemicals were screened for their physicochemical characteristics using ADME analysis. Finally, the stability of the selected compounds in their corresponding docking complexes with BTK was analysed using molecular dynamics simulations. Primarily, our observations revealed that, out of the 46 phytochemicals of O. sanctum, six compounds possessed significantly better docking scores (ranging from -9.2 kcal/mol to -10 kcal/mol). Their docking scores were comparable to those of the control inhibitors, acalabrutinib (-10.3 kcal/mol), and ibrutinib (-11.3 kcal/mol). However, after ADME analysis of these top-ranked six compounds, only three compounds (Molludistin, Rosmarinic acid, and Vitexin) possessed drug likeliness characteristics. During the MD analysis, the three compounds Molludistin, Rosmarinic acid, and Vitexin were found to remain stable in the binding pocket in their corresponding docking complexes with BTK. Therefore, among the 46 phytochemicals of O. sanctum tested in this study, the three compounds, Molludistin, Rosmarinic acid, and Vitexin are the best inhibitors of BTK. However, these findings need to be confirmed by biological experiments in the laboratory.

TFA-mediated stereoselective aza-Michael addition for the synthesis of 3ß-arylamine derivatives of withaferin A and evaluation of their anticancer potential.

A simple and efficient protocol for the aza-Michael addition of various aromatic anilines to ring A of withaferin A has been developed. Stereoselectivity, functional group tolerance, broad substrate scope, short reaction time and moderate to high yield are the merits of the protocol. One of the synthesized compounds 11 shows an IC 50 value of 3.8 µM against aggressive, highly metastatic triple-negative breast cancer cell line MDA-MB-231.

In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B-cells. In this study, bioinformatics analyses were conducted to identify possible pathogenic roles of CK2α, which is a protein encoded by CSNK2A1, in the progression and aggressiveness of CLL. Furthermore, various computational tools were used to search for a competent inhibitor of CK2α from fungal metabolites that could be proposed for CLL therapy. In CLL patients, high-expression of CSNK2A1 was associated with early need for therapy (n = 130, p < 0.0001) and short overall survival (OS; n = 107, p = 0.005). Consistently, bioinformatics analyses showed CSNK2A1 to associate with/play roles in CLL proliferation and survival-dependent pathways. Furthermore, PPI network analysis identified interaction partners of CK2α (PPI enrichment p value = 1 × 10-16) that associated with early need for therapy (n = 130, p < 0.003) and have been known to heavily impact on the progression of CLL. These findings constructed a rational for targeting CK2α for CLL therapy. Consequently, computational analyses reported 35 fungal metabolites out of 5820 (filtered from 19,967 metabolites) to have lower binding energy (ΔG: - 10.9 to - 11.7 kcal/mol) and better binding affinity (Kd: 9.77 × 107 M-1 to 3.77 × 108 M-1) compared with the native ligand (ΔG: - 10.8, Kd: 8.3 × 107 M--1). Furthermore, molecular dynamics simulation study established that Butyl Xanalterate-CK2α complex continuously remained stable throughout the simulation time (100 ns). Moreover, Butyl Xanalterate interacted with most of the catalytic residues, where complex was stabilized by more than 65% hydrogen bond interactions, and a significant hydrophobic interaction with residue Phe113. Here, high-expression of CSNK2A1 was implicated in the progression and poor prognosis of CLL, making it a potential therapeutic target in the disease. Butyl Xanalterate showed stable and strong interactions with CK2α, thus we propose it as a competitive inhibitor of CK2α for CLL therapy.

Knowledge of safe handling, administration, and waste management of chemotherapeutic drugs among oncology nurses working at Khartoum Oncology Hospital, Sudan.

Introduction: Knowledge of chemotherapeutic drug (CD) handling, administration, and waste disposal are important among nurses involved in cancer therapy. Inadequate knowledge of the management of CD could cause environmental contamination and potential harm to patients and nurses. To assess the knowledge of safe handling, administration, and waste management of CD among oncology nurses working at Khartoum Oncology Hospital, Sudan. Methods: A questionnaire was developed by a team of experts to assess the knowledge in three domains of oncology nursing practice (handling, administration, and disposal). The study involved 78 oncology nurses working in Khartoum Oncology Hospital in Sudan from April 2020. Results: The mean CD knowledge score of nurses was 12.7 ± 3.9 out of 26 items in the questionnaire. For each domain, their knowledge showed poor scores related to safe handling (mean = 2.0 ± 1.5 out of eight knowledge items) and good scores for administration (mean = 6.2 ± 1.7 out of 10) and poor scores for waste disposal (mean = 4.4 ± 1.5 out of eight). Simple linear regression indicated that education level (ß = 3.715, p = .008) and training (ß = 0.969, p = .004) significantly predicted knowledge among nurses. Conclusion: There is a significant need to enhance the knowledge and safe handling skills of CD among oncology nurses in Sudan. Implementation of strict guidelines to manage cytotoxic waste to reduce health risks and hospital contamination.

Assessment of IL-1ß, IL-6, TNF-α, IL-8, and CCL 5 levels in newly diagnosed Saudi patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle-aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro-inflammatory cytokines and chemokines can contribute to the pathogenesis of RA. AIM: In the current study, we assessed the potential of serum concentrations of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, IL-8, and C-C motif chemokine ligand (CCL)5 as early predictive markers for RA. METHODS: In addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme-linked immunosorbent assay was used to quantify the serum IL-1ß, IL-6, TNF-α, IL-8, and CCL5 levels in the samples. RESULTS: Our results indicated that RF, CRP, and ESR levels were higher in RA patients compared to controls. Furthermore, serum levels of IL-1ß, IL-6, IL-8, and CCL5, but not TNF-α, significantly increased in RA patients compared to controls. CONCLUSION: Overall, the findings suggested that IL-1ß, IL-6, IL-8, and CCL5 can be used as biomarkers in the early diagnosis of RA.

Application of innovative packaging technologies to manage fungi and mycotoxin contamination in agricultural products: Current status, challenges, and perspectives.

The consumer demand for safe, "healthy," and premium foods, preferably with an extended shelf-life; demand for easy packaging; and choice for more sustainable food packaging have contributed to the development of novel packaging technologies. The application of adequate packaging materials has recently become a major post-harvest challenge concerning the control of fungi and mycotoxin. This review will describe the current antifungal packaging technology involved to prevent the contamination of fungi and mycotoxin, along with the characteristics and mechanism of action in food products. Antifungal packaging has incredible potential in the food packaging sector. The most suitable approach for the safe storage of agricultural produce for farmers is the hermetic packaging technology, which maintains quality while providing a good barrier against fungi and mycotoxin. Furthermore, active antifungal packaging is a viable method for incorporating antifungal agents against pathogenic fungi. Essential oils and organic acid have received more scientific attention due to their increased efficacy against mold growth. Polypeptides, chitosan, and natamycin incorporated in active packaging significantly reduced fungi. Even though nanotechnological advancements in antifungal packaging are promising, safety and regulation issues remain significant concerns.

Pioneer Role of Extracellular Vesicles as Modulators of Cancer Initiation in Progression, Drug Therapy, and Vaccine Prospects.

Cancer is one of the leading diseases, causing deaths worldwide. Nearly 10 million deaths were reported in 2020 due to cancer alone. Several factors are involved in cancer progressions, such as lifestyle and genetic characteristics. According to a recent report, extracellular vesicles (EVs) are involved in cancer initiation, progression, and therapy failure. EVs can play a major role in intracellular communication, the maintenance of tissue homeostasis, and pathogenesis in several types of diseases. In a healthy person, EVs carry different cargoes, such as miRNA, lncRNA etc., to help other body functions. On the other hand, the same EV in a tumor microenvironment carries cargoes such as miRNA, lncRNA, etc., to initiate or help cancer progression at various stages. These stages may include the proliferation of cells and escape from apoptosis, angiogenesis, cell invasion, and metastasis, reprogramming energy metabolism, evasion of the immune response, and transfer of mutations. Tumor-derived EVs manipulate by altering normal functions of the body and affect the epigenetics of normal cells by limiting the genetic makeup through transferring mutations, histone modifications, etc. Tumor-derived EVs also pose therapy resistance through transferring drug efflux pumps and posing multiple drug resistances. Such EVs can also help as biomarkers for different cancer types and stages, which ultimately help with cancer diagnosis at early stages. In this review, we will shed light on EVs' role in performing normal functions of the body and their position in different hallmarks of cancer, in altering the genetics of a normal cell in a tumor microenvironment, and their role in therapy resistance, as well as the importance of EVs as diagnostic tools.

TGF-ß signaling: A recap of SMAD-independent and SMAD-dependent pathways.

Transforming growth factor-ß (TGF-ß) is a proinflammatory cytokine known to control a diverse array of pathological and physiological conditions during normal development and tumorigenesis. TGF-ß-mediated physiological effects are heterogeneous and vary among different types of cells and environmental conditions. TGF-ß serves as an antiproliferative agent and inhibits tumor development during primary stages of tumor progression; however, during the later stages, it encourages tumor development and mediates metastatic progression and chemoresistance. The fundamental elements of TGF-ß signaling have been divulged more than a decade ago; however, the process by which the signals are relayed from cell surface to nucleus is very complex with additional layers added in tumor cell niches. Although the intricate understanding of TGF-ß-mediated signaling pathways and their regulation are still evolving, we tried to make an attempt to summarize the TGF-ß-mediated SMAD-dependent andSMAD-independent pathways. This manuscript emphasizes the functions of TGF-ß as a metastatic promoter and tumor suppressor during the later and initial phases of tumor progression respectively.

Prevalence of non-specific chronic low-back pain and risk factors among male soldiers in Saudi Arabia.

BACKGROUND: Non-specific chronic low back pain (NSCLBP) is the most common musculoskeletal disorder affecting health and work among the military population. NSCLBP is a complex disorder with several risk factors contributing to its occurrence. Therefore, the objective of our study was to estimate the prevalence and contribution of risk factors towards NSCLBP among male soldiers in Saudi Arabia. METHODS: A cross-sectional study was conducted from March 2020 to January 2021 among the military personnel at Hafar Al-Batin military base, Saudi Arabia. The entire population (n = 62, 000) at the military base were invited to participate in the study. The participants were invited to participate in the study either through direct referral from in-patient and out-patient departments of the military hospital or by invitation through pamphlets, email, and advertisement across the offices and residential areas. Soldiers reporting lower back pain for at least 12 weeks were screened for inclusion criteria at the physical therapy department of the military hospital. Inclusion criteria included pain or discomfort originating from the lower back without any known spinal diseases. Participants with a systemic inflammatory disorder, trauma, neurological symptoms, and recent spinal surgery were excluded. All eligible participants were assessed for demographic variables and risk factors and complete the Rolland Morris Disability Questionnaire and WHO-Five Well-Being Index. RESULTS: This study identified a 46.3% prevalence of pain originating from the spine with a 2.7% prevalence of NSCLBP. Spearman's rho correlation between the severity of disability due to NSCLBP was strongly associated with age (rs = 0.834, p < 0.01), quality of sleep (rs = 0.790, p < 0.01), body mass index (BMI) (rs = 0.617, p < 0.01), smoking (rs = 0.520, p < 0.01), co-morbidity (rs = 0.357, p < 0.01), but not with the level of physical activity (rs = 0.044, p = 0.07). CONCLUSION: There was a high prevalence of pain originating from the spine among male Saudi soldiers with a relatively low prevalence of NSCLBP. However, the prevalence of disability due to NSCLBP was strongly associated with age, sleep quality, BMI, smoking habit, and co-morbidity.

Seroprevalence of Viral Hepatitis B and C among Blood Donors in the Northern Region of Riyadh Province, Saudi Arabia.

BACKGROUND: Hepatitis B and C viral infections, which are the most common cause of liver infection worldwide, are major health issues around the globe. People with chronic hepatitis infections remain at risk of liver cirrhosis and hepatic carcinoma, while also being a risk to other diseases. These infections are highly contagious in nature, and the prevention of hepatitis B and C transmission during blood transfusion is a major challenge for healthcare workers. Although epidemiological characteristics of hepatitis B and C infections in blood donors in Saudi Arabia have been previously investigated in multiple studies, due to targeted cohorts and the vast geographical distribution of Saudi Arabia, there are a lot of missing data points, which necessitates further investigations. AIM OF THE STUDY: This study aimed to determine the prevalence of hepatitis B and hepatitis C viral infections among blood donors in the northern region of Riyadh, Saudi Arabia. METHODS: To determine the given objectives, a retrospective study was performed which included data gathered from serological as well as nucleic acid test (NAT) screening of blood donors. Clinical data of 3733 blood donors were collected for a period of 2 years (from January 2019 to December 2020) at the blood bank of King Khalid General Hospital and the associated blood banks and donation camps in the region. Statistical analysis of the clinical data was performed using SPSS. RESULTS: The blood samples of 3733 donors were analyzed to determine the seroprevalence of hepatitis B and C among the blood donors in the northern region of Riyadh, Saudi Arabia. Among the total of 3733 blood donors, 3645 (97.65%) were men and 88 (2.36%) were women. Most of the donors were younger than 27 years of age (n = 1494). The most frequent blood group in our study was O-positive (n = 1534), and the least frequent was AB-negative (n = 29). After statistically analyzing the clinical data, we observed that 7 (0.19%), 203 (5.44%) and 260 (6.96%) donor blood samples were positive for the HBV serological markers HBsAgs, HBsAbs and HBcAbs, respectively, and 12 (0.32%) blood samples reacted positively to anti-HCV antibodies. Moreover, 10 (0.27%) and 1 (0.027%) samples were NAT-HBV positive and NAT-HCV positive, respectively. CONCLUSION: In the current study, low prevalence rates of HBV and HCV were observed in the blood donors. Statistical correlations indicated that both serological tests and NATs are highly effective in screening potential blood donors for HBV and HCV, which, in turn, prevents potential transfusion-transmitted hepatitis.

Application of new technologies in decontamination of mycotoxins in cereal grains: Challenges, and perspectives.

Emerging decontamination technologies have been attracted considerable attention to address the consumers' demand for high quality and safe food products. As one of the important foods in the human diet, cereals are usually stored for long periods, resulting in an increased risk of contamination by different hazards. Mycotoxins comprise one of the significant contaminants of cereals that lead to enormous economic losses to the industry and threats to human health. While prevention is the primary approach towards reducing human exposure to mycotoxins, decontamination methods have also been developed as complementary measures. However, some conventional methods (chemical treatments) do not fulfill industries' expectations due to limitations like safety, efficiency, and the destruction of food quality attributes. In this regard, novel techniques have been proposed to food to comply with the industry's demand and overcome conventional methods' limitations. Novel techniques have different efficiencies for removing or reducing mycotoxins depending on processing conditions, type of mycotoxin, and the food matrix. Therefore, this review provides an overview of novel mycotoxin decontamination technologies such as cold plasma, irradiation, and pulse light, which can be efficient for reducing mycotoxins with minimum adverse effects on the quality and nutritional properties of produce.

Effect of puffing on physical and antioxidant properties of brown rice.

The objective of this study was to investigate the effect of puffing process on the physical, antioxidant properties and mineral composition of brown rice. Bulk density significantly varied (P<0.05) among the puffing stages and was lowest in expanded rice. From Hunter colour analysis, the lowest L(∗) value and highest a(∗) and b(∗) values were observed for parboiled rice (P<0.05). A-type of diffraction pattern, observed in raw rice was altered by puffing process and led to the formation of B- and V-type patterns. Raman spectrum showed the intense peaks in raw rice and the intensity of those peaks was decreased during the puffing process. Scanning electron microscopy revealed a highly porous structure of expanded rice kernel. Significant decrease in the antioxidant properties was observed upon puffing process as compared to raw rice samples. Hence the present study demonstrates that the puffing process leads to the significant changes in the properties of brown rice.

Comparative study of Mirs(') (Mushtaq and Shabir) technique of prepuce preserving minimally invasive urethroplasty with Snodgrass urethroplasty for repair of distal hypospadias without chordee A prospective study.

BACKGROUND: There is no single, universally applicable technique for hypospadias repair and numerous techniques have been practised from time to time. We compare the results of our new technique (Mirs' technique also called Mush & Shab's technique) to Snodgross urethroplasty. Mirs' technique is a modified version of Thiersch-Duplay urethroplasty. MATERIAL AND METHODS: This prospective comparative study was carried out in a tertiary care hospital of Northern India over a period of 3 years from March 2010 to March 2013 and included 120 patients of anterior (distal penile, subcoronal, coronal and glanular) hypospadias without chordee. They underwent either Mirs' technique (group 1 n = 60) or Snodgrass technique (group 2 n = 60). Follow-up was at 1-week, 1-month, 3 months and 6 months. RESULTS: The mean operative time was 55 min (range: 43-70 min) in group 1 and 71.9 min (range: 60-81 min) in group 2 (P < 0.001). Urethrocutaneous fistula developed in two and four patients in group 1 and 2, respectively. Fistula closure was done at least 3 months postoperatively, and there was no significant difference in success rate between the two groups. Three cases of glanular dehiscence were detected (one in group 1 and two in group 2); the patient from group 1 had a successful repair using the already preserved prepuce. CONCLUSION: Mirs' modification of Thiersch-Duplay technique for distal hypospadias is a time saving procedure with a lower overall complication rate. Valuable local tissue is preserved to deal with any complication that may occur. Analgesic requirement was significantly lower in this minimally traumatic technique. As it is less time consuming, simple and easy to learn with a short learning curve, this technique deserves application in cases of distal hypospadias.

Role of MHC class Ib molecule, H2-M3 in host immunity against tuberculosis.

The MHC class I family comprises both classical (class Ia) and non-classical (class Ib) members. While the prime function of classical MHC class I molecules (MHC class Ia) is to present peptide antigens to pathogen-specific cytotoxic T cells, non-classical MHC-I (MHC class Ib) antigens perform diverse array of functions in both innate and adaptive immunity. Vaccines against intracellular pathogens such as Mycobacterium tuberculosis need to induce strong cellular immune responses. Recent studies have shown that MHC class I molecules play an important role in the protective immune response to M. tuberculosis infection. Both MHC Ia-restricted and MHC class Ib-restricted M. tuberculosis -reactive CD8(+) T cells have been identified in humans and mice, but their relative contributions to immunity is still uncertain. Unlike MHC class Ia-restricted CD8(+) T cells, MHC class Ib-restricted CD8(+) T cells are constitutively activated in naive animals and respond rapidly to infection challenge, hence filling the temporal gap between innate and adaptive immunity. The present review article summarizes the general host immunity against M. tuberculosis infection highlighting the possible role of MHC class Ib molecule, H2-M3 and their ligands (N-formylated peptides) in protection against tuberculosis.