Clinical and genetic characteristics of disorders of sex development in Sudanese patients

Given the scarce data on DSD in Sudan, we aimed to characterize DSD's clinical and genetic profile in Sudanese patients. We studied 60 patients with DSD using clinical data, cytogenetics, and PCR for the SRY gene. The results showed that 65% grew up as females and 35% as males. There was a high percentage of consanguineous parents (85%). Female genital mutilation (FGM) was performed in 75% of females. Patients who presented after pubertal age were 63%, with ambiguous genitalia in 61.7%, followed by primary amenorrhea (PA) in 30%. The SRY gene was positive in 3.3% of patients with 46,XX karyotype and negative in 6.7% of patients with 46,XY karyotype. 5αR2D-DSD was seen in 43.3%, gonadal dysgenesis in 21.7%, Ovotesticular syndrome in 6.7%, Swyer and Turner syndrome in 5% each, and Androgen Insensitivity Syndrome (AIS) in 3.3%. In conclusion, DSD in Sudan has a distinct profile with late presentation, dominated by 5αR2D-DSD due to the increased consanguineous marriage, and FGM represents a significant risk for DSD patients.

Compte tenu du peu de données sur le DSD au Soudan, nous avons cherché à caractériser le profil clinique et génétique du DSD chez les patients soudanais. Nous avons étudié 60 patients atteints de DSD en utilisant des données cliniques, cytogénétiques et PCR pour le gène SRY. Les résultats ont montré que 65 % ont grandi en tant que femmes et 35 % en tant qu'hommes. Il y avait un pourcentage élevé de parents consanguins (85 %). Des mutilations génitales féminines (MGF) ont été pratiquées chez 75 % des femmes. Les patientes qui se sont présentées après l'âge pubertaire étaient 63 %, avec des organes génitaux ambigus dans 61,7 %, suivis d'une aménorrhée primaire (AP) dans 30 %. Le gène SRY était positif chez 3,3 % des patients de caryotype 46,XX et négatif chez 6,7 % des patients de caryotype 46,XY. Le 5αR2D-DSD a été observé dans 43,3 %, la dysgénésie gonadique dans 21,7 %, le syndrome ovotesticulaire dans 6,7 %, le syndrome de Swyer et Turner dans 5 % chacun et le syndrome d'insensibilité aux androgènes (AIS) dans 3,3 %. En conclusion, le DSD au Soudan présente un profil distinct avec une présentation tardive, dominé par le 5αR2D-DSD en raison de l'augmentation des mariages consanguins, et les MGF représentent un risque important pour les patients DSD.

Neonatal Birthweight Spectrum: Maternal Risk Factors and Pregnancy Outcomes in Saudi Arabia.

Background and Objectives: Low-birth-weight (LBW) neonates are at increased risk of morbidity and mortality which are inversely proportional to birth weight, while macrosomic babies are at risk of birth injuries and other related complications. Many maternal risk factors were associated with the extremes of birthweight. The objectives of this study are to investigate maternal risk factors for low and high birthweight and to report on the neonatal complications associated with abnormal birth weights. Materials and Methods: We conducted a retrospective analysis of medical records of deliveries ≥ 23 weeks. We classified the included participants according to birth weight into normal birth weight (NBW), LBW, very LBW (VLBW), and macrosomia. The following maternal risk factors were included, mother's age, parity, maternal body mass index (BMI), maternal diabetes, and hypertension. The neonatal outcomes were APGAR scores < 7, admission to neonatal intensive care unit (NICU), respiratory distress (RD), and hyperbilirubinemia. Data were analyzed using SAS Studio, multivariable logistic regression analyses were used to investigate the independent effect of maternal risk factors on birthweight categories and results were reported as an adjusted odds ratio (aOR) and 95% Confidence Interval (CI). Results: A total of 1855 were included in the study. There were 1638 neonates (88.3%) with NBW, 153 (8.2%) with LBW, 27 (1.5%) with VLBW, and 37 (2.0%) with macrosomia. LBW was associated with maternal hypertension (aOR = 3.5, 95% CI = 1.62-7.63), while increasing gestational age was less likely associated with LBW (aOR = 0.51, 95% CI = 0.46-0.57). Macrosomia was associated with maternal diabetes (aOR = 3.75, 95% CI = 1.67-8.41), in addition to maternal obesity (aOR = 3.18, 95% CI = 1.24-8.14). The odds of VLBW were reduced significantly with increasing gestational age (aOR = 0.41, 95% CI = 0.32-0.53). In total, 81.5% of VLBW neonates were admitted to the NICU, compared to 47.7% of LBW and 21.6% of those with macrosomia. RD was diagnosed in 59.3% of VLBW neonates, in 23% of LBW, in 2.7% of macrosomic and in 3% of normal-weight neonates. Hyperbilirubinemia was reported in 37.04%, 34.21%, 22.26%, and 18.92% of VLBW, LBW, NBW, and macrosomic newborns, respectively. Conclusions: Most neonates in this study had normal birthweights. Maternal hypertension and lower gestational age were associated with increased risk of LBW. Additionally, maternal obesity and diabetes increased the risk of macrosomia. Neonatal complications were predominantly concentrated in the LBW and VLBW, with a rising gradient as birthweight decreased. The main complications included respiratory distress and NICU admissions.

Pulicaria crispa mitigates nephrotoxicity induced by carbon tetrachloride in rats via regulation oxidative, inflammatory, tubular and glomerular indices.

CONTEXT: Carbon tetrachloride (CCl4) induces oxidative stress in various tissues by altering antioxidants defense system. Recently, there has been a substantial use of phytotherapy to treat different diseases. OBJECTIVE: This study was designed to evaluate the curative effect of Pulicaria crispa (Forssk.) Benth et Hook (Family Asteraceae) aerial parts ethanol extract against CCl4 induced toxicity in rats kidneys. MATERIALS AND METHODS: Nephrotoxicity was induced by intraperitoneal injection with CCl4 in a dose of 0.5 mL/kg b.wt./twice a week for six consecutive weeks. Serum kidney function tests, oxidative stress markers, inflammatory cytokines, nephrotoxicity biomarkers and histopathological observation were evaluated. RESULTS: CCl4 increased serum kidney function parameters, malondialdehyde level, inflammatory cytokines, and nephrotoxicity markers, while decreased certain oxidative stress indices as superoxide dismutase and glutathione refereeing to the control group (p < 0.0001). Administration of P. crispa ethanol extract to CCl4 injured rats attenuated these changes with variable degrees. The results were confirmed through the observed amelioration of the renal histological architectures. CONCLUSION: P. crispa ethanol extract possesses potent curative effect against CCl4-induced nephropathy through improvement of kidney function, oxidative stress, inflammatory and nephrotoxicity index and the renal histopathological features. To establish the therapeutic and pharmacological applications of the plant, additional researches are required.

Urinary transferrin and proinflammatory markers predict the earliest diabetic nephropathy onset.

AIM: This study aimed to determine the earliest markers of diabetic nephropathy (DN) onset with discriminative potentials from controlled diabetes (CD). METHODS: Sixty male Wistar rats were allocated into three groups (20/group), the two diabetic groups CD and DN received 45 and 65 mg/kg STZ in 0.1 mole/L citrate buffer, respectively, while the control group received only the vehicle. Serum/urinary levels of glomerular, tubular, oxidative and proinflammatory markers were weekly monitored. RESULTS: Each diabetic group showed a different pattern of inflammatory, oxidative and signs of nephropathy along the study period, but none had a discriminative power until the fourth week. At this time point, levels of urinary transferrin, serum/urinary IL-6 and TNF-α as well as urinary IL-18 were significantly higher in DN group compared to CD (p = 0.0217, <0.0001, 0.0005, 0.0004, 0.0006, 0.0019, respectively). Predictive thresholds of these markers were calculated by receiver operating characteristic (ROC) curve that showed area under curve (AUC) of 0.9375 for transferrin with cut-off value of 35.2 mg/dL and 1.000 for serum/urinary IL-6 and TNF-α and urinary IL-18 with cut-of values 224.1, 82.11, 6.596, 125.9 and 21.86 pg/mL, respectively. CONCLUSION: Urinary transferrin and the inflammatory endpoints proposed in this study might represent promising biomarkers for the early DN onset.

Evaluation of causes of female infertility using ultrasonography in Najran, Saudi Arabia.

Descriptive cross-sectional, hospital-based study carried out at the Maternal and Childbirth Hospital, Najran, Saudi Arabia, from May 2020 to May 2021 Using Ultrasonography. This study assessed the causes of female infertility by evaluating 100 women with infertility who attended the hospital. The mean age of the women with infertility was 34.8 ± years, with most between 35 -44 years 49%, 31% between 25-34 years old, 11% between 15 - 24 years old and 19% were ≥45were. Of the sample, 65% had primary infertility, while 35% had secondary infertility. A statistical significant association was found between age and the type of infertility (p < 0.05) with polycystic ovary disease being the most common cause of infertility 56%, followed by fibroids 22%, Endometrial polyps 9%, Adenomyosis 5%, Hydrosalpinx 4%, Congenital abnormality 2% and other causes was 1%. Our findings demonstrate the usefulness of ultrasound in diagnosing and evaluating female infertility. The cause of female infertility are polycystic ovary disease, fibroids, Endometrial polyps, Adenomyosis, Hydrosalpinx and congenital anomalies.

Impact of betanin against paracetamol and diclofenac induced hepato-renal damage in rats.

Context: Paracetamol (PAR) and diclofenac (DF) are the most popular consumed analgesics and anti-inflammatory medications.Objective: This study aimed to explore the protective effect of betanin (Bet) against PAR or DF induced hepato-renal damage in rats.Methods: Rats were randomly divided into five groups: Normal control (NC) group rats were given saline only. PAR group rats received PAR (400 mg/kg). PAR/Bet treated group rats administered PAR (400 mg/kg) plus Bet (25 mg/kg). DF group rats received DF (10 mg/kg). DF/Bet treated group rats administered DF (10 mg/kg) plus Bet (25 mg/kg). All drugs were given by gavage for 28 consecutive days.Results: PAR and DF administration in high dose and long-time induced liver and kidney injury, disrupted serum lipid profile, enhanced serum levels of inflammatory and oxidative stress markers, triggered DNA fragmentation and caused drastic changes in the histopathological pictures of the two organs. Bet supplementation succeeded to ameliorate most of the biochemical changes and protected DNA from damage as obtained from comet assay. Histological features in H&E taken to different groups also mirrors this findings.Conclusion: Bet exerted a potential anti-inflammatory and antioxidant effect against hepato-renal damage induced by PAR or DF overconsumption.

Protective effects of betanin against paracetamol and diclofenac induced neurotoxicity and endocrine disruption in rats.

Context: Overconsumption of paracetamol (PAR) and diclofenac (DF) have been reported to induce neurotoxicity and endocrine disruption. Objective: The current study was designed to explore the protective potential of betanin against PAR and DF inducing neurotoxicity and endocrine disruption in a rat model. Material and Methods: Forty rats were equally divided into five groups: group I served as control, group II received PAR (400 mg/kg), group III received PAR plus betanin (25 mg/kg), group IV received DF (10 mg/kg) and group V received DF plus betanin orally for 28 consecutive days. Thyroid axis hormones, sex hormone, neurotransmitters, paraoxonase-1, hemeoxygenase-1 and nuclear factor-2 were measured by ELISA. While, the oxidative stress markers were colorimetrically estimated. Moreover, DNA damage and histopathological picture of the brains were investigated. Results: A marked reduction in thyroid axis hormones, brain neurotransmitters and serum testosterone as well as enhanced oxidative stress and brain DNA damage accompanied by drastic changes in the brain histopathological picture were recorded in the challenged PAR and DF groups. Betanin supplementation ameliorated most of the biochemical and histopathological changes induced by PAR or DF. Conclusion: The study suggests betanin of potential protective effects against neurotoxicity and endocrine disruption induced by PAR and DF overconsumption.

Camel whey protein protects lymphocytes from apoptosis via the PI3K-AKT, NF-κB, ATF-3, and HSP-70 signaling pathways in heat-stressed male mice.

Heat stress (HS) is an environmental factor that depresses the immune systems that mediate dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. This study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were distributed among 3 groups: control group; HS group; and HS mice that were orally administered CWP (HS + CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, tumor necrosis factor-α) as well as a significant reduction in the IL-2 and IL-4 levels. Exposure to HS resulted in impaired phosphorylation of AKT and IκB-α (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha); increased expression of activating transcription factor 3 (ATF-3) and 70 kDa heat shock proteins (HSP70); and aberrant distribution of CD3+ T cells and CD20+ B cells in the thymus and spleen. Interestingly, HS mice treated with CWP presented significantly restored levels of reactive oxygen species and pro-inflammatory cytokines near the levels observed in the control mice. Furthermore, supplementation of HS mice with CWP enhanced the phosphorylation of AKT and IκB-α; attenuated the expression of ATF-3, HSP70, and HSP90; and improved T and B cell distributions in the thymus and spleen. Our findings reveal a potential immunomodulatory effect of CWP in attenuating immune dysfunction induced by exposure to thermal stress.

Protective effects of camel whey protein against scrotal heat-mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR-gamma signaling pathways.

Elevation of scrotal temperature is one of the most important causes of impaired spermatogenesis and male infertility, but the exact mechanism remains controversial. The present study investigated the impact of camel whey protein (CWP) on the mechanisms of heat stress (HS)-mediated testicular damage in male mice. Exposure to HS was associated with significant increase in the testicular tissues' oxidative stress. Mechanistically, exposure to HS resulted in upregulation of P53 and Nrf2 expressions; downregulation of Bcl2 and PPAR-γ expressions; and induction of testicular Leydig cell hyperplasia. Because Leydig cells produce testosterone up on stimulation with Luteinizing hormone (LH), HS mice also exhibited significant reduction in the serum testosterone levels followed by significant reduction in the percentages of progressively motile sperm and higher percentages of immotile sperm, when compared with those of control mice. Interestingly, treatment of HS mice with CWP significantly restored the levels of ROS and the activities of antioxidant enzymes in the testicular tissues nearly to those observed in control mice. Furthermore, CWP supplemented HS mice exhibited complete restoration of Bcl2, P53, Nrf2, and PPAR-γ expressions; testicular Leydig cell distribution; significant higher levels of testosterone levels; and hence higher percentages of progressively motile sperm and lower percentages of immotile sperm as compared to HS mice. Our findings reveal the protective effects of CWP against testis injury and infertility induced by exposure to HS by rescuing functional Leydig cells. Additionally, the present study has shed light on the molecular mechanisms underlying improved testicular damage following CWP treatment.

Correlation of trans fatty acids with the severity of coronary artery disease lesions.

BACKGROUND: Nutritional choices, which include the source of dietary fatty acids (FA), have an important significant impact on coronary artery disease (CAD). We aimed to determine on patients with CAD the relationships between Trans fatty acids (Trans FA) and different CAD associated parameters such as inflammatory and oxidative stress parameters in addition to Gensini score as a vascular severity index. METHODS: Fatty acid profiles were established by gas chromatography from 111 CAD patients compared to 120 age-matched control group. Lipid peroxidation biomarkers, oxidative stress, inflammatory parameters and Gensini score were studied. RESULTS: Our study showed a significant decrease of the antioxidant parameters levels such as erythrocyte glutathione peroxydase (GPx) and superoxide dismutase (SOD) activities, plasma antioxidant status (FRAP) and thiol (SH) groups in CAD patients. On the other hand, catalase activity, conjugated dienes and malondialdehyde were increased. Plasmatic and erythrocyte Trans FA were also increased in CAD patients compared to controls. Furthermore, divergent associations of these Trans FA accumulations were observed with low-density lipoprotein-cholesterol/ high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio, Apolipoprotein B (ApoB), lipid peroxidation parameters, high-sensitivity C Reactive Protein (hs-CRP), Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and Gensini score. Especially, elaidic acid (C18:1 trans 9), trans C18:2 isomers and trans 11 eicosanoic acid are correlated with these parameters. Trans FA are also associated with oxidative stress, confirmed by a positive correlation between C20:1 trans 11 and GPx in erythrocytes. CONCLUSIONS: High level of Trans FA was highly associated with the induction of inflammation, oxidative stress and lipoperoxidation which appear to be based on the vascular severity and might be of interest to assess the stage and progression of atherosclerosis. The measurement of these Trans FA would be of great value for the screening of lipid metabolism disorders in CAD patients.

Quality of care provided to children with cerebral palsy, Alexandria, Egypt.

BACKGROUND: Assessing the quality of care has become increasingly important to health care providers, regulators and purchasers of care. AIMS: This study assessed the quality of care provided to children with cerebral palsy attending Alexandria University Children's Hospital, Egypt. METHODS: Paediatric neurology residents (n = 15) who provided care to children with cerebral palsy at the hospital completed a structured checklist assessing their compliance with generic care standards. The medical records of 84 children with cerebral palsy who received care at the hospital were reviewed using the same checklist. Another checklist was completed by the head of the paediatric neurology unit, medical director of the hospital, head of physical medicine and head nurse to assess adherence to process and service improvement standards. Face-to-face interviews were conducted with the caregivers/parents of the children using a client satisfaction questionnaire. RESULTS: Based on what was reported by health care providers, most did not adhere to the recommended practices in the care of children with cerebral palsy. Review of the medical records also showed a lack of compliance with standards. The mean total satisfaction percentage score of parents/caregivers was 55.43% (SD 18.16). Satisfaction was particularly low for waiting time, waiting area and availability of required facilities for their child's care. CONCLUSIONS: There is a wide gap between the actual care provided to children with cerebral palsy and the recommended standards. Moreover, the documentation system in the hospital is poor. A quality improvement plan is needed for the provision of care to children with cerebral palsy.

Identification of long and very long chain fatty acids, plasmalogen-C16:0 and phytanic acid as new lipid biomarkers in Tunisian coronary artery disease patients.

Long and very long chain fatty acids (LCFAs and VLCFAs) may play an active role in coronary artery diseases (CAD) etiology. Our aim was to evaluate the associations between LCPUFAs (C20:4n-6; C20:5n-3 and C22:6n-3) and VLCSFAs (C22:0, C24:0; and C26:0), as well as markers of peroxisomal integrity evaluated by phytanic acid and plasmalogen-C16:0 (PL-C16:0) in addition to the markers of lipid peroxidation (malondialdehyde [MDA] and conjugated dienes [CD]) and inflammation (high sensitivity C-reactive protein [hs-CRP]) with vascular severity evaluated by Gensini score in order to determine their possible effects on CAD in Tunisian population. Lipidomic strategy based on GC/MS-SIM was used to quantify LCPUFAs, VLCSFAs, and PL-C16:0 in red blood cells of CAD patients, non-CAD patients, and controls. We observed a significant increase in phytanic acid, PL-C16:0 and VLCFAs, particularly C26:0, in CAD group compared to controls. Further our findings showed positive correlations of C26:0 with MDA and with vascular severity score (Gensini score). In addition, a significant negative correlation was shown between hs-CRP and C22:6 n-3 (r=-0.297; p=0.002) and a significant positive association was observed between hs-CRP and C20:4 n-6 levels (r=0.196; p=0.039). Our results show changes in LCPUFAs and VLCSFAs concentrations in RBC among study groups, and suggest alterations in fatty acids metabolism regulated by elongase and desaturase enzymes. The positive correlations of C20:4n-6 and the negative correlations of C22:6n-3, simultaneously with Gensini score and hs-CRP, suggest a link of both inflammation and vascular severity complication of CAD with LCPUFAs and VLCSFAs. Induction of lipid oxidation, can be one of the outcomes of LCFAs and VLCFAs accumulation in vascular tissues and, thus, playing an important role in the pathogenesis of atherosclerosis. Quantification of LCPUFAs and VLCSFAs, phytanic acid and PL-C16:0 simultaneously, would be of great value for the screening of peroxisomal disorders in vascular tissue of CAD patients.

Role of disturbed fatty acids metabolism in the pathophysiology of diabetic erectile dysfunction.

BACKGROUND: Vasculogenic erectile dysfunction (VED) is considered as a common complication among people with type 2 diabetes (T2D). We tested whether changes in fatty acid (FAs) classes measured in erythrocytes are associated with increased risk of diabetic VED along with related risk factors. METHODS: We assessed erythrocyte FAs composition, lipid peroxidation parameters and inflammatory cytokines among 72 T2D men with VED, 78 T2D men without VED and 88 healthy volunteers with similar age. Biochemical, hepatic, lipid and hormonal profiles were measured. RESULTS: T2D people with VED had significant decrease in the indexes of Δ6-desaturase and elongase activities compared to the other studied groups. The same group of participants displayed lower erythrocytes levels of dihomo-γ-linolenic acid (C20:3n-6) (P < .001), precursor of the messenger molecule PGE1 mainly involved in promoting erection. Moreover, absolute SFAs concentration and HOMA IR levels were higher in T2D people with VED when compared to controls and associated with impaired NO concentration (1.43 vs 3.30 ng/L, P < .001). Our results showed that IL-6 and TNF-α were significantly increased and positively correlated with MDA levels only in T2D people with VED (r = 0.884, P = .016 and r = 0.753, P = .035; respectively) suggesting a decrease in the relative availability of vasodilator mediators and an activation of vasoconstrictors release. CONCLUSION: Our findings show that the deranged FAs metabolism represents a potential marker of VED in progress, or at least an indicator of increased risk within men with T2D.

Association of plasma fatty acid alteration with the severity of coronary artery disease lesions in Tunisian patients.

BACKGROUND: Some factors related to diet are known to be involved in the progression of atherosclerosis in humans. METHODS: The relationship between plasma fatty acid (FA) levels and the severity of coronary artery disease (CAD), evaluated by Gensini score (GS), was investigated in CAD Tunisian patients compared to controls. Lipid profiles were analyzed, GS was calculated in CAD and non-CAD patients and compared to controls. RESULTS: CAD patients showed an alteration of conventional lipid parameters. In fact, a significant increase of plasmatic triglycerides (TG) level, atherogenic lipid ratios (TC/HDL-C,TG/HDL-C, LDL-C/HDL-C); and ApoB/ApoA1 was observed in the CAD group comparatively to controls (p < 0.001). Gensini score was showed to be a good indicator to evaluate cholesterol metabolism disorders associated with HDL-C since a negative association was found between HDL-C levels and GS for the two groups of patients. In addition, in the relation with FA and classes of FA, a negative association was found as expected, between Gensini score and total MUFA, PUFA n-3, total PUFA, GLA, DGLA and DHA. Furthermore, a positive association with stearic and erucic acid was found. Suggests that, GS is also a good indicator to evaluate FA metabolic disorders. Higher elongation index and modifications of desaturation index (D5D, D6D and D9D) were observed in patients compared to controls, supporting FA metabolism modifications. CONCLUSIONS: In conclusion, although that Tunisian population appears to follow the Mediterranean diet, variations of plasmatic FA levels and desaturase activities in CAD patients highlights an alteration of FA metabolism and suggests an important implication of certain FA in the development of atherosclerosis.

Evidence of biological activity of Mentha species extracts on apoptotic and autophagic targets on murine RAW264.7 and human U937 monocytic cells.

CONTEXT: Mints (Lamiaceae) are used as traditional remedies for the treatment of several diseases. Their extracts are recognized as anti-inflammatory compounds. OBJECTIVE: This study characterized the cytotoxic effects of Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L). Huds (MR) on macrophage cells (RAW264.7; U937) and determined their impact on apoptosis and autophagy, which can play a role in controlling inflammation. MATERIALS AND METHODS: The extracts were prepared in culture medium and tested from 25 to 400 µg/mL after 24-48 h of treatment. To show the effect of the aqueous ethanol (50%) extracts on apoptosis and authophagy, the presence of cleaved caspase-3, and the conversion of LC3-I to LC3-II was evaluated by Western blotting. RESULTS: Compared with the MTT assay, crystal violet showed a pronounced decrease in the number of cells with all extracts at 48 h. Calculated IC50 values were 257.31, 207.82 and 368.02 µg/mL for MS, MP and MR, respectively. A significant increase in PI positive cells was observed with all extracts at 200-400 µg/mL. Mitochondrial dysfunctions and nuclear morphological changes were detected with MS and MR extracts at 400 µg/mL. At this concentration, no cleaved caspase-3 was found whereas stabilized caspase-3 in its dimeric form was identified. MS and MR extracts also favour LC3-I to LC3-II conversion which is a criterion of autophagy. CONCLUSIONS: The cytotoxic profiles depend on the extracts considered; MS extract showed the strong activity. However, all the mint extracts studied interact with the apoptotic and autophagic pathways at elevated concentrations.

Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate.

The treatment of microglial BV-2 cells with sodium arsenate (As(V): 0.1-400µmol/L - 48hr) induces a dose-dependent response. The neurotoxic effects of high concentrations of As(V) (100, 200 and 400µmol/L) are characterized by increased levels of mitochondrial complexes I, II, and IV followed by increased superoxide anion generation. Moreover, As(V) triggers an apoptotic mode of cell death, demonstrated by an apoptotic SubG1 peak, associated with an alteration of plasma membrane integrity. There is also a decrease in transmembrane mitochondrial potential and mitochondrial adenosine triphosphate ATP. It is therefore tempting to speculate that As(V) triggers mitochondrial dysfunction, which may lead to defective oxidative phosphorylation subsequently causing mitochondrial oxidative damage, which in turn induces an apoptotic mode of cell death.

Clinical utility of certain biomarkers as predictors of breast cancer with or without metastasis among Egyptian females.

The objective of this study is to explore and correlate the value of certain biomarkers in breast cancer (BC) females with and without metastasis after undergoing the surgical treatment protocol in the National Cancer Institute in Egypt. Thirty females (33-69 years), diagnosed as early breast cancer patients with or without metastasis, and 20 healthy individuals were selected for this study. The biomarkers under investigation were vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-8 (IL-8). The correlation between these markers and the tumor grade was also evaluated. The results revealed a significant increase (p < 0.0001) in VEGF, CRP, IL-6, and IL-8 in breast cancer patients with or without metastasis as compared to the healthy group. Surgical treatment of metastatic BC females showed a significant reduction of those parameters by variable degrees, whereas BC females without metastasis recorded the most inhibition levels. Also, there was positive correlation (p < 0.0001) between those biomarkers and the tumor grades. We also noticed an association between VEGF and IL-8 as well as CRP and IL-6. In conclusion, the selected biomarkers may be beneficial for the prognosis of breast cancer and seem to be a diagnostic tool to differentiate between BC with or without metastasis. The descried surgical treatment protocol succeeded to attenuate the elevated biomarker levels and improve patient survival which deserves more extensive studies.

Evaluation of lupine seeds (Lupinus albus L.) neutral extract as a texture improver in low-fat yogurt production.

Aqueous lupine seeds (Lupinus albus L.) extracts were evaluated as a natural fat substitute in low-fat yogurt production. Thus, the chemical composition, particle size, molecular weight, total phenolic (TPC), and total flavonoids (TFC) of the selected extract were estimated. Also, the antimicrobial activity and antioxidant capacity of selected extract were investigated. Yogurt with neutral lupine extract (NeLP) had the highest all sensorial attributes compared to other extracts. Also, the incorporation of NeLP during low-fat yogurt processing increased the solid content, and viscosity, as well as improved the textural profile and sensorial attributes without any negative effect on the yogurt's color. SEM micrographs of NeLP-yogurt microstructure showed a matrix characterized by large fused casein micelles clusters with comparatively lower porosity compared to control yogurt (without NeLP). The chemical composition of NeLP indicated that the major sugar constituents are glucose and galactose with different molar fractions. The molecular weight of NeLP is 460.5 kDa with a particle size of 1519.9 nm. Also, IC50 of NeLP is 0.589 mg/ml, while TPC and TFC are 7.17, and 0.0137 g/100 g sample, respectively. Hence, lupine neutral extract (0.25%) could be used as a fat replacer or texture improver ingredient in such low-fat yogurt which led to improved its characteristics without any negative defect during 7 days at 5 °C.

Multistage in silico approach to identify novel quinoline derivatives as potential c-kit kinase inhibitors.

The type II-C-KIT signaling network has been extensively studied for its potential as a target for cancer treatment, leading to the investigation of quinoline derivatives as compounds with inhibitory effects on c-Kit kinase. In this study, a multistage approach was employed, including the creation of pharmacophore models, 3D QSAR analysis, virtual screening, docking investigations, and molecular dynamics stimulation. The pharmacophore evaluation included a data set of 29 ligands, which resulted in the generation of the ADDHR_1pharmacophore model as the most promising, with a survival score of 5.6812. The main objective was to utilize the atom-based 3D-QSAR approach for generating robust 3D-QSAR models aimed at identifying new TypeII-C-kit kinase inhibitors. The evaluations of these models have convincingly demonstrated their high predictive power (Q2 = 0.6547, R2 = 0.9947). Using atom-based 3D-QSAR data, a total of 7564 novel compounds were generated from R-group enumeration. Molecular docking and MM-GBSA study revealed that compound A1 exhibited the highest binding score of -9.30 kcal/mol and a Δ GBind value of -90.56 kcal/mol. The ZINC compounds were then screened using the pharmacophore model, followed by virtual screening, which identified ZINC65798256, ZINC09317958, ZINC73187176, and ZINC76176670 as potential candidates with promising docking scores. Among these, ZINC65798256 demonstrated the best binding interactions with amino acid residues, ASP810, LYS623, CYS673, and THR670 (PDB ID: 1T46). To further analyze the structural features and molecular interactions, molecular dynamics simulation was conducted for a time scale of 100 ns.Communicated by Ramaswamy H. Sarma.

Thymoquinone Nanoparticles (TQ-NPs) in Kidney Toxicity Induced by Ehrlich Ascites Carcinoma (EAC): An In Vivo Study.

Background: Cisplatin (Cis) is potent chemotherapy used to treating already many different types of cancer; however, it is found to correlate with nephrotoxicity and other adverse health consequences. Thymoquinone (TQ) is an antioxidant and anti-inflammatory molecule that may defend against the consequences of different chemotherapies. Thymoquinone uses, although, are negatively impacted by its weak solubility and inadequate biological availability. Objectives: This investigation examined the efficacy of a new nanoparticle (NP) absorbing TQ in an Ehrlich Ascites Carcinoma (EAC) mice model to address its low solubility, enhance its bioavailability, and protect against Cis-induced nephrotoxicity. Methods: Following 4 treatment groups were included in this research: (1) control, (2) EAC, (3) EAC + Cis + Thymoquinone nanoparticle (TQ-NP) treated, and (4) EAC + Cis-treated. Results: The study revealed that TQ-NP was efficacious in avoiding Cis-induced kidney problems in EAC mice, as well as restoring kidney function and pathology. Thymoquinone nanoparticle considerably reduced Cis-induced oxidative damage in renal tissue by augmenting antioxidant levels. According to tumor weight and histological investigation results, TQ-NP did not impair Cis's anticancer efficacy. Conclusion: Thymoquinone nanoparticle might be used as a potential drug along with Cis anticancer therapy to reduce nephrotoxicity and other side effects while maintaining Cis anticancer properties.

Contexte: Le cisplatine (CIS) est un puissant agent chimiothérapeutique utilisé pour le traitement de nombreux types de cancers. Le cisplatine est cependant corrélé à de la néphrotoxicité et à d'autres conséquences néfastes pour la santé. La thymoquinone (TQ) est une molécule antioxydante et anti-inflammatoire qui peut protéger contre les effets néfastes de différents agents chimiothérapeutiques. Les faibles solubilité et biodisponibilité de la TQ limitent toutefois son utilisation. Objectifs: Un modèle de souris atteintes d'un carcinome ascitique d'Ehrlich (souris EAC) a servi à vérifier l'efficacité d'une nouvelle nanoparticule (NP) absorbant la TQ pour remédier aux faibles solubilité et biodisponibilité de la TQ et protéger contre la néphrotoxicité induite par le CIS. Méthodologie: Les quatre groupes suivants ont été examinés: i) témoin; ii) souris EAC; iii) souris EAC traitées par CIS + TQ-NP (thymoquinone-nanoparticule); iv) souris EAC traitées par CIS. Résultats: L'étude a révélé que la TQ-NP était efficace pour éviter les problèmes rénaux induits par le CIS chez les souris EAC, de même que pour restaurer la fonction rénale et soigner la pathologie. En augmentant les niveaux d'antioxydants, la TQ-NP a considérablement réduit les dommages oxydatifs induits par le CIS dans le tissu rénal. Selon le poids des tumeurs et les résultats de l'étude histologique, la TQ-NP n'a pas altéré l'efficacité anticancéreuse du CIS. Conclusion: La TQ-NP pourrait potentiellement être utilisée avec le traitement anticancéreux par CIS afin de réduire la néphrotoxicité et les autres effets secondaires, sans altérer les propriétés anticancer du CIS.