Biomedical students' self-efficacy and academic performance by gender in a flipped learning haematology course.

INTRODUCTION: This study investigated the impact of flipped learning versus traditional instruction on medical students' academic performance and self-efficacy in a haematology course, and examined gender differences. Flipped learning is an instructional approach where students review pre-recorded lecture content at home, and active learning occurs in the classroom. Self-efficacy refers to students' beliefs in their ability to succeed and accomplish learning goals. METHODS: A quasi-experimental study was conducted with 86 third-year Saudi medical students (46 males, 40 females) in a 10-week haematology course. Students were assigned to flipped learning group (n = 41) or traditional lecture group (n = 45). Both groups completed pre- and post-intervention academic tests and self-efficacy surveys. Data were analyzed using descriptive statistics and t-tests. RESULTS: The flipped learning group showed an increase in academic scores (p <.05) and self-efficacy scores (p <.05) compared to the traditional group, but between group differences were not statistically significant. Female students in the flipped learning group showed the greatest increase in academic scores and self-efficacy. Most students perceived flipped learning positively for enhancing learning and preparation for class. CONCLUSION: Flipped learning promoted self-efficacy compared to traditional lectures in medical students. Gender-specific benefits were observed, highlighting the need to design instruction to meet diverse student needs.

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.

The Therapeutic Potential of Milk Extracellular Vesicles on Colorectal Cancer.

Colorectal cancer remains one of the leading prevalent cancers in the world and is the fourth most common cause of death from cancer. Unfortunately, the currently utilized chemotherapies fail in selectively targeting cancer cells and cause harm to healthy cells, which results in profound side effects. Researchers are focused on developing anti-cancer targeted medications, which is essential to making them safer, more effective, and more selective and to maximizing their therapeutic benefits. Milk-derived extracellular vesicles (EVs) from camels and cows have attracted much attention as a natural substitute product that effectively suppresses a wide range of tumor cells. This review sheds light on the biogenesis, methods of isolation, characterization, and molecular composition of milk EVs as well as the therapeutic potentials of milk EVs on colorectal cancer.

Distal femoral valgus cut angle in degenerative varus knees of an Arabic population.

PURPOSE: This study aimed to determine the natural distribution of the distal femoral valgus cut angle (VCA) among an Arabic population; the percentage of patients whose VCA fell within the range of 5-6°; and whether demographic variables, severity of the pre-operative varus, and morphological femoral parameters would correlate with the VCA. To our knowledge, VCA measurement of degenerative varus knees among an Arabic population has not been reported previously in the literature. METHODS: A total of 492 knees (246 patients) were included. The VCA was measured on pre-operative hip-to-ankle radiographs according to a standard protocol. Patient characteristics and radiographic parameters were recorded. RESULTS: The mean VCA was 6.03 ± 1.69°, with 230 knees (46.7%) falling within the (5-6°) range. The VCA significantly differed according to the patient's age (p = 0.02), sex (p = 0.009), height (p = 0.03), degree of varus (p < 0.001), hip offset (p = 0.013), and the presence of excessive lateral coronal bowing of the femur (p = 0.01). Among these, the degree of varus was the only significant factor on the multivariable regression analysis (p = 0.005). CONCLUSION: The mean VCA in our population was 6.03°; however, the wide distribution of the VCA in our patients does not support the use of a fixed value. The severity of the pre-operative varus seems to be an independent factor with a positive correlation to the VCA and may also provide a clue to the ideal VCA if measurement of this angle is not available.

Pes anserinus pain syndrome following total knee arthroplasty for degenerative varus: incidence and predictors.

PURPOSE: Pes anserinus pain syndrome (PAPS) is a well-described condition in the native knee; however, its incidence after total knee arthroplasty (TKA) is unknown. This study aimed to determine the incidence of PAPS after primary TKA, identify potential risk factors, and assess its response to treatment. Few case reports have been published until now; to our knowledge, ours is the first study assessing the incidence and predictors of post-TKA PAPS. METHODS: A total of 389 primary TKAs performed for degenerative varus knee at a single institution by the same surgeon were analyzed. We recorded demographic variables, medical comorbidities, and clinical, radiographic, and surgical data. Specific predictors of interest were compared between post-TKA PAPS and controls. RESULTS: The incidence was 5.6% (22/389). On univariate analysis, female sex (p = 0.03), body mass index (BMI) (41.3% ± 7.9; p < 0.001), and absence of pes anserinus release (p = 0.04) were significant predictors. On multivariable regression analysis, only BMI was a significant independent risk factor (p = 0.01). All patients were treated non-operatively; 81.8% responded to nonsteroidal anti-inflammatory drug-physical therapy program and 18.2% required an additional local steroid injection. CONCLUSION: PAPS occurs after TKA; the incidence was found to be 5.6%. BMI seems to be an independent risk factor. It is a benign condition and can be effectively treated conservatively in most cases.

Arabic translation, cultural adaptation, and validation study of Knee Outcome Survey: Activities of Daily Living Scale (KOS-ADLS).

Knee complaints and their accompanying functional impairments are frequent problems encountered by healthcare practitioners worldwide. Plenty of functional scoring systems were developed and validated to give a relative estimation about the knee function. Despite the wide geographic distribution of Arabic language in the Middle East and North Africa, it is rare to find a validated knee function scale in Arabic. The present study is aimed to translate, validate, and culturally adjust the Knee Outcome Survey: Activities of Daily Living Scale (KOS-ADLS) into Arabic language for future use among Arabic-speaking patients. Permission for translation was obtained from the copyrights holder. Two different teams of high-level clinical and linguistic expertise conducted translation process blindly. Forward-backward translation technique was implemented to ensure preservation of the main conceptual content. Main study consisted of 280 subjects. Reliability was examined by test-retest pilot study. Visual Analogue Scale (VAS), Get Up and Go (GUG) Test, Ascending/Descending Stairs (A/D Stairs), and Subjective Assessment of Function (SAF) were conducted concurrently to show the validity of Arabic KOS-ADLS statistically in relation to these scales. Final translated version showed no significant discrepancies. Minor adaptive adjustment was required to fit Arabian cultural background. Internal consistency was favourable (Cronbach's alpha 0.90). Patients' scoring on Arabic KOS-ADLS appeared relatively consistent with their scoring on VAS, GUG, A/D Stairs, and SAF. A significant linear relationship was demonstrated between SAF and total KOS-ADLS scores on regression analysis (adj. R 2 = 0.548). Arabic KOS-ADLS, as its English counterpart, was found to be a simple, valid, and useful instrument for knee function evaluation. Arabic version of KOS-ADLS represents a promising candidate for unconditional use among Arabic-speaking patients with knee complaints.

Correction of severe pelvic obliquity using maximum-width segmental sacropelvic screw fixation: an analysis of 20 neuromuscular scoliosis patients.

STUDY DESIGN: The present study was a retrospective analysis. OBJECTIVE: The purpose of the study was to evaluate the safety and efficacy of the maximum-width (M-W) segmental sacropelvic fixation technique, comprising iliac screws and/or iliosacral pedicle screws, to correct severe pelvic obliquity. Classic spinal fixation using the Luque-Galveston procedure for the correction of neuromuscular scoliosis may be inadequate to manage severe pelvic obliquities. METHODS: A series of 20 consecutive patients with severe neuromuscular spinopelvic deformities was reviewed by an independent observer. Coronal and sagittal Cobb angle, frontal pelvic obliquity, and trunk shift were measured preoperatively, immediately postoperatively and at final follow-up. RESULTS: All 20 patients underwent spinal fusion with instrumentation extending to the pelvis. Fourteen cases had primary operations, and six patients had undergone previous spinal fusion above the pelvis, requiring extension to the pelvis. The mean age of the patients at surgery was 13 years, and the mean duration of the follow-up period was 36 months. The mean preoperative Cobb angle was 84° (range 56°-135°), which was corrected to a mean of 41° (range 8°-75°) postoperatively. At the final follow-up, the mean spinal curve remained at 42° (range 10°-75°). The mean preoperative pelvic obliquity was 42° (range 15°-105°), which was corrected by 78 % to 9° (range 0°-49°) postoperatively, with a pelvic obliquity of 10° (range 2°-49°) at final follow-up. Comparing the results of the present study with results in the literature describing the Luque-Galveston or unit rod techniques, despite patients in the present study having a greater mean pelvic obliquity (42° compared with 21° in the literature), a 78 % correction was still achieved, which is similar and, in certain instances, superior to the results of other published case series (78 % compared with 53 %). CONCLUSIONS: Maximum-width (M-W) segmental sacropelvic fixation, comprising iliosacral screws and/or iliac screws, enables a superior correction of severe pelvic obliquity in patients with neuromuscular scoliosis.

Comparative study of hamstring and quadriceps strengthening treatments in the management of knee osteoarthritis.

[Purpose] Osteoarthritis (OA) of the knee is the most common form of joint disease. It is one of the major causes of impaired function that reduces quality of life (QOL) worldwide. The purpose of this study was to compare exercise treatments for hamstring and quadriceps strength in the management of knee osteoarthritis. [Subjects and Methods] Forty patients with OA knee, aged 50-65 years were divided into 2 groups. The first group (57.65±4.78 years) received hot packs and performed strengthening exercises for the quadriceps and hamstring, and stretching exercises for the hamstring. The second group (58.15±5.11 years) received hot packs and performed strengthening exercises for only the quadriceps, and stretching exercise for the hamstring. Outcome measures were the WOMAC (Western Ontario and McMaster Universities OA index questionnaire), Visual Analogue Scale (VAS) assessment of pain, the Fifty-Foot Walk Test (FWS), and Handheld dynamometry. [Results] There was a significant difference between the groups. The first group showed a more significant result than the second group. [Conclusion] Strengthening of the hamstrings in addition to strengthening of the quadriceps was shown to be beneficial for improving subjective knee pain, range of motion and decreasing the limitation of functional performance of patients with knee osteoarthritis.

Effect of forward and backward locomotion training on anaerobic performance and anthropometrical composition.

[Purpose] Forward walking (FW) and backward walking (BW) on a treadmill is a common tool for lower extremity rehabilitation in the clinical setting. The purpose of this study was to evaluate the effects on anaerobic performance and anthropometrical adaptations during FW and BW on a treadmill. [Subjects and Methods] A convenience sample of thirty healthy male subjects with a mean age of 20.93 ± 2.54 years participated in this study. Subjects were divided into 2 groups, a Forward Walking Group (FWG) (n=15) and a Backward Walking Group (BWG) (n=15), which performed FW and BW on a treadmill at 10° inclination, respectively. The training consisted of three sessions per week for 6 weeks. Study outcomes such as anaerobic performance and anthropometrical body composition were measured at pre- and post-intervention. [Results] Both FW and BW improved anaerobic performance significantly, and the BW group showed better performance than FW. However, changes in anthropometrical body composition were found to be not significant after six weeks of intervention in both the FW and BW groups. [Conclusions] BW training in rehabilitation can be considered more effective than FW at improving anaerobic performance. We also conclude that six weeks of FW and BW training is insufficient for eliciting changes in the body composition.

Arabic Translation of the Knee Outcome Survey-Sports Activities Scale With Cross-cultural Adaptation and Validation.

Background: There are few sports-specific knee functional scales in the Arabic language. The Knee Outcome Survey-Sports Activities Scale (KOS-SAS) is a validated sports-specific patient-reported outcome measure that assesses knee function in an athletic population. Purpose: To provide a validated Arabic version of the KOS-SAS (KOS-SAS-Ar) while achieving cross-cultural adaptation for use in an Arabic-speaking population with sports-related knee disorders. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: There were 2 independent translators who conducted a forward translation of the KOS-SAS, followed by a backward translation by different translators. Subsequently, researchers and expert invitees judged the conceptual content and cultural adaptations of the final translation. A total of 276 patients completed the KOS-SAS-Ar as well as the International Knee Documentation Committee (IKDC) subjective assessment of knee function and a visual analog scale (VAS) for pain. Statistical analysis was performed for test-retest reliability, convergent validity, construct validity, and factor analysis. Results: The test-retest reliability of the KOS-SAS-Ar was high (r = 0.9). The items of the KOS-SAS-Ar had statistically significant internal consistency, with a Cronbach alpha of .924 (P < .0001). The KOS-SAS-Ar Symptoms subscore correlated with the VAS pain score (P < .0001), and the KOS-SAS-Ar Functional Limitations subscore correlated with the IKDC subjective score (P < .0001). The construct validity of the KOS-SAS-Ar was satisfactory (Kaiser-Meyer-Olkin value = 0.868; Bartlett test: P < .0001). Factor analysis showed a statistical correlation among the 11 items of the KOS-SAS-Ar. Conclusion: The KOS-SAS-Ar demonstrated favorable reliability and validity, and it appears to be a suitable tool for Arabic-speaking patients with sports-related knee conditions.

Protein C and protein S deficiencies are associated with increased risk of deep vein thrombosis in pregnant women using oral contraceptives.

BACKGROUND: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). OBJECTIVE: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT). MATERIALS AND METHODS: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed. RESULTS: The study found that women with DVT had significantly lower levels of PC and PS compared with controls ( P  < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS. CONCLUSION: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

Assessment of risk factors for deep vein thrombosis associated with natural anticoagulants and fibrinolytic regulatory proteins.

Deep vein thrombosis (DVT) is a critical condition and a potential cause of mortality and morbidity in Africa and worldwide with a high recurrence rate. The study was designed to assess the roles of natural anticoagulants and fibrinolytic regulatory factors in the development of DVT in Sudanese patients. A case-control study was conducted in Omdurman Teaching Hospital, Khartoum State over a period of 1 year. The study enrolled 200 patients diagnosed with DVT and 200 age-matched and gender-matched controls. Demographic data and data on acquired risk factors were collected using a semi-structured questionnaire. Protein C (PC), protein S (PS), antithrombin III (AT-III), thrombin-activable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor-1 (PAI-1) were measured in patients and controls. Among the patients with DVT, 5.5% had PC deficiency, 8.5% had PS deficiency, and 3% had AT-III deficiency. Elevated TAFI and PAI-1 levels were demonstrated in 1.5 and 0.5% of patients, respectively. Risk factors for DVT (overweight, surgical history, and family history of DVT) were remarkably higher in patients than in controls. Among the female participants, pregnancy and usage of oral contraceptive pills were the highest associated risk factors for DVT. The findings concluded that the early assessment of risk factors, including the measurements of natural inhibitors, can predict the occurrence of DVT before it is actually detected in patients.

Green Synthesis and Anticancer Potential of 1,4-Dihydropyridines-Based Triazole Derivatives: In Silico and In Vitro Study.

A library of 1,4-dihydropyridine-based 1,2,3-triazol derivatives has been designed, synthesized, and evaluated their cytotoxic potential on colorectal adenocarcinoma (Caco-2) cell lines. All compounds were characterized and identified based on their 1H and 13C NMR (Nuclear Magnetic Resonance) spectroscopic data. Furthermore, molecular docking of best anticancer hits with target proteins (protein kinase CK2α, tankyrase1, and tankyrase2) has been performed. Our results implicated that most of these compounds have significant antiproliferative activity with IC50 values between 0.63 ± 0.05 and 5.68 ± 0.14 µM. Moreover, the mechanism of action of most active compounds 13ab' and 13ad' suggested that they induce cell death through apoptosis in the late apoptotic phase as well as dead phase, and they could promote cell cycle arrest at the G2/M phase. Furthermore, the molecular docking study illustrated that 13ad' possesses better binding interaction with the catalytic residues of target proteins involved in cell proliferation and antiapoptotic pathways. Based on our in vitro and in silico study, 13ad' was found to be a highly effective anti-cancerous compound. The present data indicate that dihydropyridine-linked 1,2,3-triazole conjugates can be generated as potent anticancer agents.

Association of TNF-α rs1800629 with Adult Acute B-Cell Lymphoblastic Leukemia.

TNF−α influences lymphomagenesis by upregulating proinflammatory and antiapoptotic pathways. In this study, we evaluated the frequency of TNF−α rs1800629 (−308 G>A) polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and its correlation with age at diagnosis, gender and subtype of ALL. In this case control study, a total of 330 individuals were recruited, including 165 newly diagnosed adult patients with ALL, from the Radiation and Isotope Center in Khartoum (RICK) and 165 healthy normal controls. TNF−α rs1800629 polymorphism was tested through allele-specific polymerase chain reaction (PCR) assay. The frequency of the rs1800629 GA genotype was high (70.9% vs. 60%, OR = 1.84) in the patient group as compared to healthy controls, whereas GG and AA genotypes did not exhibit any statistically significant difference between controls and patients. Based on subtype, GG and GA rs1800629 genotypes showed increased risk of B-ALL (OR 0.46 and 2.12, respectively), whereas rs1800629 GG, GA and AA genotypes did not show any disease association with T-ALL (p > 0.05). Age at diagnosis and gender did not exhibit any association of rs1800629 with ALL in the patient group. In conclusion, rs1800629 is associated with high risk of adult B-ALL, with an insignificant effect of age at diagnosis and gender.

Sulindac acetohydrazide derivative attenuates against cisplatin induced organ damage by modulation of antioxidant and inflammatory signaling pathways.

This study aimed to explore the mechanisms of action of a sulindac acetohydrazide derivative, N'-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide, against anticancer drug cisplatin induced organ damage. Using a rodent model, various markers of organ function and signaling pathways were examined and validated by molecular docking studies. The study involves five groups of animals: control, DMSO, CDDP, CDDP + DMFM, and DMFM. Biochemical enzyme activity, histopathology, tissue antioxidant, and oxidative stress markers were examined. RT-PCR and western blot analyses were conducted for the expression of inducible cyclooxygenase enzyme (COX-2), nuclear factor kappa beta (NF-κB), p65, IL-1, TNF-α, and inducible nitric oxide synthase (iNOS). Flow cytometry analysis of CD4 + TNF-α, CD4 + COX-2, and CD4 + STAT-3 cells in whole blood was performed. Structural and dynamic behavior of DMFM upon binding with receptor molecule molecular docking and dynamic simulations were performed using bioinformatics tools and software. Treatment with DMFM reversed cisplatin-induced malondialdehyde (MDA) and nitric oxide (NO) induction, whereas the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD) in the kidney, heart, liver, and brain tissues were increased. DMFM administration normalized plasma levels of biochemical enzymes. We observed a marked decline in CD4 + STAT3, TNF-α, and COX2 cell populations in whole blood after treatment with DMFM. DMFM downregulated the expression factors related to inflammation at the mRNA and protein levels, i.e., IL-1, TNF-α, iNOS, NF-κB, STAT-3, and COX-2. Dynamic simulations and in silico docking data supports the experimental findings. Our experimental and in silico results illustrated that DMFM may affect protective action against cisplatin-induced brain, heart, liver, and kidney damage via reduction of inflammation and ROS.

IL-10 rs1800896 Polymorphism: A Risk Factor for Adult Acute Lymphoblastic Leukemia.

Purpose: Single-nucleotide polymorphism (SNP) in the promoter region of the IL-10 gene can increase susceptibility to tumor development. The current study aimed to explore the genotypic frequency of interleukin-10 (IL-10) rs1800896 polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and validate whether this SNP is a risk factor for adult ALL. Patients and Methods: This case-control study was based on a subset of newly diagnosed 154 adult patients with ALL recruited from the Radiation and Isotope Center in Khartoum (RICK) and 154 healthy controls from the same geographical area. Genomic DNA was used for the genotyping of rs1800896 polymorphism through allele-specific polymerase chain reaction (PCR) assays. Results: The genotypic frequencies of rs1800896 showed a statistically significant association of AG and AA genotypes with adult ALL (p<0.001). Combined genotypes AG+GG vs AA also showed a positive association of rs1800896 with adult ALL (OR=4.89). The allelic frequencies of G and A did not show any significant difference in adult patients with ALL compared with the control group. AG rs1800896 genotype showed an increased risk of B and T ALL (OR=2.51 and 4.70, respectively). Age at diagnosis, gender, and immunophenotype (B vs T ALL) did not exhibit any association of rs1800896 with ALL in this patient group. Conclusion: rs1800896 polymorphism is associated with an increased risk of ALL in adult patients irrespective of the age at diagnosis, gender, and immunophenotype of ALL.

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism.

Purpose: Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL. Patients and Methods: This case-control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using ß-globin gene as an internal positive control. Results: The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42-29.74, P < 0.001). Conclusion: Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.

Therapeutic potential of camel milk exosomes against HepaRG cells with potent apoptotic, anti-inflammatory, and anti-angiogenesis effects for colostrum exosomes.

This study aimed to evaluate and compare the therapeutic effect of camel milk exosomes derived from colostrum, early, mid, and late lactation periods on liver cancer HepaRG cells. These exosomes showed cytotoxicity on HepaRG while being safer on normal human liver THLE-2 cells. Among the four different isolated exosome groups, exosomes isolated from colostrum exhibited the highest apoptotic potential on HepaRG as indicated by highest DNA damage and upregulated expression of Bax and caspase3 expression, but with lowest Bcl2 expression. HepaRG-treated with colostrum-derived exosomes also exhibited the lowest expression of inflammation-related genes (TNFα, NFkB, TGFß1, and Cox2) and the angiogenesis-related gene VEGF. Colostrum-derived exosomes had significantly higher expression of lactoferrin and kappa casein than other milk-derived exosomes. These results indicate that colostrum-derived exosomes have a more potent anti-cancer effect on HepaRG cells than exosomes derived from the early, mid, and lat lactation periods. This effect could be mediated through induction of apoptosis and inhibition of inflammation and angiogenesis. Therefore, these exosomes could be used as safe adjuvants/carriers to deliver chemotherapeutics and to potentiate their anticancer effect on liver cancer cells.

Age- and Gender-Independent Association of XRCC1 Arg399Gln Polymorphism with Chronic Myeloid Leukemia.

PURPOSE: DNA damage to hematopoietic progenitor cells is an essential factor for leukemia development as a failure of the host DNA repair system to fix errors in DNA. This study aimed to assess the association of XRCC1 gene polymorphisms including Arg194Trp, Arg399Gln, and Arg280His with the risk of development of CML in Sudanese population. PATIENTS AND METHODS: The present study was conducted on 186 newly diagnosed patients with CML, aged 19-70 years (118 males and 68 females; mean age of 46.15±13.91 years) and 186 normal healthy controls (123 males and 63 females; mean age of 44.94±8.97 years). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the XRCC1 (Arg194Trp, Arg399Gln, and Arg280His) gene polymorphisms. RESULTS: The genotypic frequencies of Arg399Gln polymorphism in cases were 131 (70.4%) homozygous Arg/Arg, 46 (24.7%) homozygous Gln/Gln, and 9 (4.8%) heterozygous Arg/Gln as compared to the controls ie, 153 (82.3%), 73 (14.5%), and 6 (3.2%), respectively. The Arg399Gln variant genotypic frequencies significantly differed between the cases and controls (χ 2 = 7.249, P = 0.027). By comparison, no statistically significant difference was observed in the variant genotype frequencies between the cases and controls in terms of Arg194Trp and Arg280His polymorphisms. CONCLUSION: XRCC1 Arg399Gln gene polymorphism might have an important role in increasing the risk of chronic myeloid leukemia among Sudanese patients. Furthermore, all tested three polymorphisms showed no association of risk of the development of CML with age and gender.

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.

PURPOSE: Glutathione S-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML. PATIENTS AND METHODS: This case-control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers. RESULTS: GSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys. CONCLUSION: In conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.