Synthesis, DFT, molecular dynamics, and Monte Carlo simulation of a novel thiourea derivative with extraordinary inhibitive properties for mild steel in 0.5 M sulphuric acid.

A novel thiourea derivative has been successfully synthesized via green routes and fully characterized by FT-IR, 1H, 13C-NMR, and elemental analysis. The synthetic inhibitor 2-amino-N-(phenylcarbamothioyl) benzamide (APCB) was assessed as a corrosion inhibitor for mild steel (MS) in 0.5 M H2SO4. Various electrochemical techniques, such as electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP), have been used to evaluate inhibition efficiency. As a result, EIS and PDP agreed with each other, indicating that APCB exhibits an inhibition performance that exceeds 96% at a concentration of 2 × 10-4 M and increases with an increase in temperature up to 98% at 333 K. However, PDP measurements showed that APCB is a mixed type of inhibitor. In addition, SEM, EDX, AFM, and contact angle measurements were used as a topological surface characterization technique that confirmed the formation of a protective layer over the MS surface. Additionally, the complex formation was thoroughly confirmed by UV-Vis measurements. The adsorption of APCB proved the highest compliance with the Langmuir adsorption isotherm. Furthermore, density functional theory (DFT) calculations were conducted to establish the correlation between the electronic structure and excellent inhibition efficiency. Moreover, molecular dynamics (MD) simulations were used to find interaction energy in different media. Finally, the adsorption affinity of the MS surface for different concentrations of APCB was verified via Monte Carlo (MC) simulations. Owing to the outcomes of this study, it is remarkable that APCB, with its low cost and simple synthesis, might be an exceptionally prominent option for mild steel protection.

Standardized statement for the ethical use of human cadaveric tissues in anatomy research papers: Recommendations from Anatomical Journal Editors-in-Chief.

Human cadaveric donors are essential for research in the anatomical sciences. However, many research papers in the anatomical sciences often omit a statement regarding the ethical use of the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To rectify this issue, 22 editors-in-chief of anatomical journals, representing 17 different countries, developed standardized and simplified language that can be used by authors of studies that use human cadaveric tissues. The goal of these editor recommendations is to standardize the writing approach by which the ethical use of cadaveric donors is acknowledged in anatomical studies that use donor human cadavers. Such sections in anatomical papers will help elevate our discipline and promote standardized language use in others non anatomy journals and also other media outlets that use cadaveric tissues.

Curcumin and ustekinumab cotherapy alleviates induced psoriasis in rats through their antioxidant, anti-inflammatory, and antiproliferative effects.

INTRODUCTION: Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects. OBJECTIVE: The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model. MATERIALS AND METHODS: Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis. RESULTS: Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (p < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant (p < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3. CONCLUSIONS: Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Comparative study of the in vivo toxicity and pathophysiology of envenomation by three medically important Egyptian snake venoms.

Snakebite envenomation is a serious medical problem in many developing tropical and subtropical countries. Envenomation is registered by the World Health Organization as a neglected tropical disease due to critical shortages in the production of antivenom. Envenomation causes more than 100,000 deaths annually. Snakebites result in several effects to include edema, blistering, hemorrhage, necrosis and respiratory paralysis. Antivenom is the preferred treatment for the systemic effects of snakebite envenomation, though these are often ineffective in neutralizing venom toxin-induced local tissue damage. To effectively treat snakebites, it is important to determine the lethal potency and pathophysiological effects induced by specific snake venoms. In the current study, we compared the lethality, and the hemorrhagic and dermonecrotic activities of venoms from three snakes in Egypt that are the primary causes of local tissue necrosis. Our data show that the intraperitoneal median lethal doses (LD50) for Cerastes cerastes, Echis carinatus and Naja nigricollis venoms are 0.946, 1.744 and 0.341 mg/kg mouse body weight, respectively. These results indicated that N. nigricollis venom is the most toxic and significantly accelerated the time of death compared to the other two venoms. However, no hematoma or associated edema appeared upon sub-plantar injection of N. nigricollis venom into the mice hind paw. Two hours following intradermal injection of C. cerastes and E. carinatus venoms, macroscopic analysis of the inner surface of mouse skin showed severe hemorrhagic lesions, whereas only insignificant hemorrhagic lesion appeared in mice injected with the highest dose of N. nigricollis venom. Furthermore, the minimum necrotic doses (MND) for the same venoms were 43.15, and 70.87 µg/mouse, or not observed in the case of N. nigricollis venom, respectively. These LD50 values and pathophysiological results can be used to guide development of antivenom against bites by these dangerous Egyptian snakes.

Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas.

Autophagy plays a critical role in tumorigenesis, but how autophagy contributes to cancer cells' responses to chemotherapeutics remains controversial. To investigate the roles of autophagy in malignant gliomas, we used CRISPR/CAS9 to knock out the ATG5 gene, which is essential for autophagosome formation, in tumor cells derived from patients with glioblastoma. While ATG5 disruption inhibited autophagy, it did not change the phenotypes of glioma cells and did not alter their sensitivity to temozolomide, an agent used for glioblastoma patient therapy. Screening of an anticancer drug library identified compounds that showed greater efficacy to ATG5-knockout glioma cells compared to control. While several selected compounds, including nigericin and salinomycin, remarkably induced autophagy, potent autophagy inducers by mTOR inhibition did not exhibit the ATG5-dependent cytoprotective effects. Nigericin in combination with ATG5 deficiency synergistically suppressed spheroid formation by glioma cells in a manner mitigated by Ca2+ chelation or CaMKK inhibition, indicating that, in combination with autophagy inhibition, calcium-mobilizing compounds contribute to efficient anticancer therapeutics. ATG5-knockout cells treated with nigericin showed increased mitochondria-derived reactive oxygen species and apoptosis compared to controls, indicating that autophagy protects glioma cells from mitochondrial reactive oxygen species-mediated damage. Finally, using a patient-derived xenograft model, we demonstrated that chloroquine, a pharmacological autophagy inhibitor, dramatically enhanced the efficacy of compounds selected in this study. Our findings propose a novel therapeutic strategy in which calcium-mobilizing compounds are combined with autophagy inhibitors to treat patients with glioblastoma.

Treatment of Gigantomastia Using a Medial-Lateral Bipedicle Reduction Mammoplasty: The Role of Doppler-Assisted Preoperative Perforator Identification.

The purpose of this study is to introduce a breast reduction technique designed to reduce the incidence of postoperative nipple-areola complex ischemia and necrosis following reduction mammoplasty, while at the same time allowing all the other goals of breast reduction to be realized. This is achieved through preoperative detection of perforating vessels supplying the nipple-areola complex using a hand-held Doppler. The horizontally based parenchymal pedicle is designed to include these perforators whether originating from the internal mammary artery, lateral thoracic artery or both. This technique provides freedom in pedicle shaping and fixation to the pectoral fascia to achieve the best breast contour. The study included 50 patients equally divided into two groups: the study group (using preoperative Doppler for detection of perforators) and control group (without preoperative Doppler). The average body mass index of our patients was 32.4 and 29.8 for study and control groups, respectively. The average suprasternal notch to nipple distance was 40.8 cm in the study group and 38.9 cm in the control group. In all cases of the study group, both medial and lateral pedicles were used each of them containing one perforator. The average resection weight per side was 1433.6 g for the study group and 1173.2 g for the control group. None of the study group cases experienced NAC necrosis, while four cases of the control group experienced NAC necrosis (3 partial and 1 total). The horizontally based parenchymal pedicle constructed with the aid of preoperative perforator identification with a Doppler is an effective technique for breast reduction that results in a very low rate of postoperative ischemia and necrosis of the nipple-areola complex. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Therapeutic Strategy for Targeting Aggressive Malignant Gliomas by Disrupting Their Energy Balance.

Although abnormal metabolic regulation is a critical determinant of cancer cell behavior, it is still unclear how an altered balance between ATP production and consumption contributes to malignancy. Here we show that disruption of this energy balance efficiently suppresses aggressive malignant gliomas driven by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation. In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production. Inhibition of mitochondrial ATP synthetase was more effective in repressing sphere formation by Tsc1-deficient glioma cells than that by Tsc1-competent glioma cells, indicating a crucial function for mitochondrial bioenergetic capacity in GIC expansion. To translate this observation into the development of novel therapeutics targeting malignant gliomas, we screened drug libraries for small molecule compounds showing greater efficacy in inhibiting the proliferation/survival of Tsc1-deficient cells compared with controls. We identified several compounds able to preferentially inhibit mitochondrial activity, dramatically reducing ATP levels and blocking glioma sphere formation. In human patient-derived glioma cells, nigericin, which reportedly suppresses cancer stem cell properties, induced AMPK phosphorylation that was associated with mTORC1 inactivation and induction of autophagy and led to a marked decrease in sphere formation with loss of GIC marker expression. Furthermore, malignant characteristics of human glioma cells were markedly suppressed by nigericin treatment in vivo Thus, targeting mTORC1-driven processes, particularly those involved in maintaining a cancer cell's energy balance, may be an effective therapeutic strategy for glioma patients.

A Simplified Method for Management of Platysmal Bands: Platysmotomy as an Office Procedure.

Restoration of the esthetic neck contour is an integral component of facial rejuvenation. Characters of the aging neck include lipodystrophy, platysmal bands and jowls that extend into the neck, reducing the esthetic characters of the lower face. The authors present a new, simplified and economic method to manage platysmal bands as an office procedure under local anesthesia using a standard 18-gauge syringe needle as a cutting tool. The new technique was used on a selected group of female patients classified as non-surgical cases according to Rorich classification. Twenty-five female patients shared in this study, with a follow-up period standardized to 1 year; one patient showed up after 1.5 years with preserved esthetic outcome. One patient showed residual band managed by recutting immediately after bruising and edema resolved. The technique was proven safe regarding important neurovascular structures of the neck. Patients gave no negative comments regarding results of surgery. Kappa statistical analysis showed perfect interobserver agreement between patients and an independent assessor. The authors concluded that the studied new technique is safe, effective, and valuable for management of platysmal bands in a selected group of patients. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of the immuno-stimulatory effect of aqueous neem (Azadirachta indica) leaf extract against highly pathogenic avian influenza (H5N8) in experimental chickens.

The recently detected clade 2.3.4.4 of the highly pathogenic avian influenza (HPAI) H5N8 virus in poultry encouraged us to study the efficacy of the 6 most extensively used saleable H5 poultry vaccinations (bivalent [AI + ND], Re-5 H5N1, H5N1, H5N3, monovalent AI, monovalent ND) with or without aqueous 8% neem (Azadirachta indica) leaf extract as an immunostimulant. One hundred thirty birds were randomly divided into 7 groups. Groups 1, 2, 3, 4, 5, and 6 were divided into 2 subgroups (G1a, G2a, G3a, G4a, G5a, G6a) and (G1b, G2b, G3b, G4b, G5b, G6b) with 10 birds each. Subgroups (G1a, G2a, G3a, G4a, G5a, G6a) received the (bivalent [AI + ND], Re-H5N1, H5N1, H5N3, monovalent AI, monovalent ND) vaccines, while subgroups (G1b, G2b, G3b, G4b, G5b, G6b) received the same previous vaccination but treated with neem leaf extract administrated 2 d before and after vaccination, and G7 with 10 birds was kept unvaccinated as positive control group. Clinical signs of the challenged group showed conjunctivitis, closed eyes, cyanosis in comb and wattle, ocular discharge, and greenish diarrhea, while postmortem lesions showed congested trachea and lung, hemorrhage on the shank, proventriculus, and pancreas; gelatinous fluid submandibular, congestion of all organs (septicemia), mottled spleen. The clinical signs and lesions were mild in neem leaf extract treated with bivalent vaccine and Re-H5N1 while moderate in monovalent vaccine and H5N3 with or without neem leaf extract treated and reached severe in the group immunized with H5N1 with or without neem leaf extract treatment. The protection levels in the bivalent vaccine (AI + ND), Re-5 H5N1, and H5N3 treated with neem leaf extract, were 80%, 80%, and 60%, respectively, while bivalent vaccine (AI + ND), Re-5 H5N1 and H5N3 without treatment were 60%, 60%, and 40%, respectively. The virus shedding was prevented in groups vaccinated with bivalent vaccine and Re-H5N1 vaccine treated with neem leaf extract, while decreased in the group vaccinated with H5N3 with neem leaf extract and Re-H5N1 without neem leaf extract compared with H5N3, H5N1, and monovalent vaccine. The immunological response after vaccination was stronger in the bivalent vaccine group than in the other commercial vaccine groups treated with neem leaf extract, with geometric mean titer (GMTs) of 315.2 and 207.9 at the third and fourth weeks, respectively. The use of immunostimulant antiviral medicinal plants, such as neem, completely protected chicken flocks against HPAI (H5N8) and prevented AI virus shedding, leading us to the conclusion that the use of bivalent vaccines induces a higher immune response than other different commercial vaccines.

Prevalence of dementia in Al Kharga District, New Valley Governorate, Egypt.

BACKGROUND: With aging, there is a parallel increase in the prevalence of dementia worldwide. The aim of this work is to determine the prevalence of dementia among the population of Al Kharga District, New Valley, Egypt. METHODS: Screening of all subjects aged ≥50 years (n = 8,173 out of 62,583 inhabitants) was done through a door-to-door survey by 3 neurologists, using a short standardized Arabic screening test and a modified Mini-Mental State Examination. Suspected cases were subjected to full clinical examination, psychometric assessment using the Cognitive Abilities Screening Instrument, Instrumental Activities of Daily Living Scale, Geriatric Depression Scale, Hachinski Ischemic Score, DSM-IV-TR diagnostic criteria, neuroimaging, and laboratory investigations, when indicated. RESULTS: The prevalence rate of dementia was 2.26% for the population aged ≥50 years. It increased steeply with age to a maximum of 18.48% for those aged ≥80 years. Alzheimer's disease (51.2%) was the most common subtype, followed by vascular dementia (28.7%), dementia due to general medical conditions (12.8%), and lastly dementia due to multiple etiologies (7.3%). Mild dementia was the commonest (53.7%). CONCLUSION: Dementia is prevalent in Egypt as elsewhere. Detection through a door-to-door survey is the best method in developing countries for early detection of mild cases.

Anatomical variations of the human sural nerve and its role in clinical and surgical procedures.

The sural nerve is the most commonly nerve used in nerve transplantation, and so the aim of this study was to determine the variations of the sural nerve in the back of the leg, its relations to the calcaneal tendon and lateral malleolus, and determine the patterns of its distribution on the dorsum of the foot. Twenty-four Egyptian legs and feet were dissected. The results showed that the sural communicating nerve connected with the sural nerve in 87.5%. The predominant site of union between these two nerves was in the lower one-third of the leg and ankle region (62%). There was only one right leg that the sural nerve passed through the gastrocnemius. The small saphenous vein passed along the medial side of the sural nerve in 100%. The sural nerve crossed the lateral border of the calcaneal tendon in 50%. The distance between the sural nerve and insertion of calcaneal tendon was 16 + 7 mm in 91.7%. There were four types of pattern of innervation of the toes by the sural nerve. The predominant pattern was type I (45.8%), where the lateral side of the little toe was supplied by the sural nerve alone. The second pattern was type IV (29.2%), where the lateral 2 ½ toes were supplied by the sural nerve alone. These findings are important for sural nerve biopsy and grafts, surgical repair of the calcaneal tendon, and regional anesthesia of the foot.

The potency of newly development H5N8 and H9N2 avian influenza vaccines against the isolated strains in laying hens from Egypt during 2019.

Avian influenza (AI) is a respiratory disease complex syndrome recently recorded in vaccinated flocks causing high economic losses. This study aimed to prepare inactivated vaccine from recently isolated field strains [highly pathogenic avian influenza (HPAI) (H5N8) and low pathogenic avian influenza (LPAI) (H9N2)] and compare the efficiency of the two experimental avian influenza vaccines and some commercial avian influenza H5 and H9N2 vaccines in laying hens. The obtained results indicated that the identified experimental vaccines (H5N8 and H9N2) were protected the flocks from AI as compared to commercial H5N1, H5N3, and H9N2 vaccines, which showed a protection level of 80, 70, and 90%, respectively, indicating a high efficacy for the developed vaccines. In addition, it significantly improved the virus shedding, especially when used in booster dose. The experimental vaccines were given high antibody titer higher than commercial vaccine which was reached to 9.3 log2, 9.7log2 for experimental H5N8 vaccine which was significantly higher than and groups 3 and 4 especially at 2nd WPV, while at the 3rd WPV, the significant difference was with group 4 only. The HI titer was 9.3 log2 at 2nd WPV for the experimental H9N2 vaccine that was significantly higher than group 9. In conclusion, the booster dose of the experimental vaccines could elicit strong immunity than single-dose and commercial vaccines.

Depletion of CIP2A inhibits the proliferation, migration, invasion and epithelial-mesenchymal transition of glioma cells.

CIP2A is an oncoprotein that is overexpressed in multiple solid tumours and some malignant haematologic disorders. However, its function in glioma is poorly understood. In this study, our results demonstrated that the expression of CIP2A was higher in glioma tissues than in normal tissues. Using tissue microarrays for immunohistochemistry, we found that the intensity of CIP2A expression was higher in high-grade gliomas (grade III-IV) than in low-grade gliomas (grade I-II). In addition, we found that depletion of CIP2A inhibited glioma cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Taken together, our findings revealed that CIP2A was involved in glioma progression, indicating that CIP2A could be used as a potential therapeutic target in the future.

Could Mesna and Celery Seed Cotherapy Modulate Oxidative Stress and Inflammation of the Urinary Bladder Induced by Ifosfamide in Rabbits?

BACKGROUND: Ifosfamide (IFS) has potential complications such as nephropathy and hemorrhagic cystitis (HC). Although mesna can prevent IFS-induced cystitis by direct binding and neutralization of acrolein, HC symptoms have still been observed clinically in most of these cases. Celery is a powerful healing vegetable that has antioxidant, anti-inflammatory, and anticancer effects. The current study evaluated the synergistic effects of mesna and celery seed on IFS-induced HC in rabbits. METHODS: Twenty male rabbits (four groups) were administered distilled water, IFS, mesna, and mesna+celery seed cotherapy (MCC) for three weeks. The serum and urinary bladder of experimental rabbits underwent biochemical (TNF-α, MDA, iNOS, SOD, GPx, and CAT), histopathological and ultrastructural investigations to evaluate the structural changes of the urinary bladder (UB). RESULTS: IFS injection resulted in severe cystitis with a remarkable increase in the scale of hematuria, elevations of TNF-α, MDA, and iNOS activity, and reduced activity of SOD, GPx, and CAT antioxidants. Additionally, the structure of UB exhibited evident mucosal edema and ulceration. In contrast, the MCC regimen group revealed partial synergistic improvement of all mentioned parameters. CONCLUSION: IFS induced cystitis by releasing acrolein, which exerted a significant role in the pathogenesis of HC. In contrast, the MCC intake partially ameliorated the UB damage through its antioxidant and anti-inflammatory effects.

Door-to-door survey of major neurological disorders in Al Kharga District, New Valley, Egypt: methodological aspects.

Epidemiology of neurological disorders is still lacking in Egypt. The door-to-door method is the most suitable one to screen neurological disorders in our country. Over a 4-year period (June 1, 2005 to May 31, 2009), screening and examination had been carried out to ascertain the incidence and prevalence rate of epilepsy, stroke, cerebral palsy and Bell's palsy, as well as the prevalence of dementia, extrapyramidal syndromes, muscle and neuromuscular disorders, cerebellar ataxia and primary nocturnal enuresis among the urban and rural population of Al Kharga District, New Valley, Egypt. A total of 62,583 people were screened by 3 neurologists in a door-to-door manner, including every door, using a standardized Arabic questionnaire to detect any patient with a neurological disorder. This was a project study of neurological disorders including 3 stages: first stage (June 1, 2005 to May 31, 2006) for data collection, designing a standardized questionnaire and screening; second stage (June 1, 2006 to May 31, 2008) for case ascertainment, classification of neurological disorders and investigations, and third stage (June 1, 2007 to May 31, 2009) for data entry and statistical analysis. The results of this study revealed that the total prevalence rate of neurological disorders in Al Kharga District, New Valley was 2.4/100 with no significant difference among both sexes. The highest prevalence rate was recorded among elderly people (60+ years; 9.25%) and among children (≤18 years; 2.9%).

Epidemiology of major neurological disorders project in Al Kharga district, New Valley, Egypt.

BACKGROUND/METHODS: A door-to-door ('every door') study was carried out to assess the incidence and prevalence rates of epilepsy, stroke, Bell's palsy and cerebral palsy, as well as the prevalence of dementia, extrapyramidal syndromes, muscle and neuromuscular disorders, cerebellar ataxia and primary nocturnal enuresis among the urban and rural populations of Al Kharga district, New Valley, Egypt. The study was carried out in 3 stages from June 1, 2005 to May 31, 2009. A door-to-door screening including every door was carried out using a standardized questionnaire, which was administered by 3 neurologists to all inhabitants (62,583) of Al Kharga district. The study was designed to assess the prevalence, incidence and risk factors of major neurological disorders in Al Kharga district and aimed to reduce the burden of these neurological disorders in the entire region. RESULTS/CONCLUSIONS: This study clarified that dementia, primary nocturnal enuresis, epilepsy, stroke and cerebral palsy are the most common neurological disorders. On the other hand, Bell's palsy, extrapyramidal syndromes, cerebellar ataxia, muscle dystrophies and myasthenia gravis are less common neurological disorders in Al Kharga district.

Identification of two mitochondrial-targeting cyclometalated iridium(III) complexes as potent anti-glioma stem cells agents.

Glioma stem cells (GSCs) are thought to be responsible for the recurrence and invasion of glioblastoma multiform (GBM), which have been evaluated and exploited as the therapeutic target for GBM. Cyclometalated iridium(III) complexes have been demonstrated as the potential anticancer agents, however, their antitumor efficacies against GSCs are still unknown. Herein, we investigated the antitumor activity of two cyclometalated iridium(III) complexes [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2) (ppy = 2-phenylpyridine, thpy = 2-(2-thienyl)pyridine and L = 4,4'-Bis(hydroxymethyl)-2,2'-bipyridine) against GSCs. The results clearly indicate that Ir1 and Ir2 kill GSCs selectively with IC50 values ranging from 5.26-9.05 µM. Further mechanism research display that Ir1 and Ir2 can suppress the proliferation of GSCs, penetrate into GSCs efficiently, localize to mitochondria, and induce mitochondria-mediated apoptosis, including the loss of mitochondrial membrane (MMP), elevation of intracellular reactive oxygen species (ROS) and caspases activation. Moreover, Ir1 and Ir2 can destroy the GSCs self-renewal and unlimited proliferation capacity by affecting the GSCs colony formation. According our knowledge, this is the first study to investigate the anti-GSCs properties of cyclometalated iridium(III) complexes.

Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression.

Hematopoietic stem cells (HSCs) in a steady state can be efficiently purified by selecting for a combination of several cell surface markers; however, such markers do not consistently reflect HSC activity. In this study, we successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. We found that the phenotypically defined long-term (LT)-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo. Within the LT-HSC population, NS-GFPhigh cells exhibited significantly higher repopulating capacity than NS-GFPlow cells. Gene expression analysis revealed that nine genes, including Vwf and Cdkn1c (p57), are highly expressed in NS-GFPhigh cells and may represent a signature of HSCs, i.e., a stemness signature. When LT-HSCs suffered from remarkable stress, such as transplantation or irradiation, NS-GFP intensity was downregulated. Finally, we found that high levels of NS-GFP identified HSC-like cells even among CD34+ cells, which have been considered progenitor cells without long-term reconstitution ability. Thus, high NS-GFP expression represents stem cell characteristics in hematopoietic cells, making this system useful for identifying previously uncharacterized HSCs.

6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections.

Loss of Tsc1 accelerates malignant gliomagenesis when combined with oncogenic signals.

Glioblastomas frequently harbour genetic lesions that stimulate the activity of mammalian target of rapamycin complex 1 (mTORC1). Loss of heterozygosity of tuberous sclerosis complex 1 (TSC1) or TSC2, which together form a critical negative regulator of mTORC1, is also seen in glioblastoma; however, it is not known how loss of the TSC complex affects the development of malignant gliomas. Here we investigated the role of Tsc1 in gliomagenesis in mice. Tsc1 deficiency up-regulated mTORC1 activity and suppressed the proliferation of neural stem/progenitor cells (NSPCs) in a serial neurosphere-forming assay, suggesting that Tsc1-deficient NSPCs have defective self-renewal activity. The neurosphere-forming capacity of Tsc1-deficient NSPCs was restored by p16(Ink4a)p19(Arf) deficiency. Combined Tsc1 and p16(Ink4a)p19(Arf) deficiency in NSPCs did not cause gliomagenesis in vivo. However, in a glioma model driven by an active mutant of epidermal growth factor receptor (EGFR), EGFRvIII, loss of Tsc1 resulted in an earlier onset of glioma development. The mTORC1 hyperactivation by Tsc1 deletion accelerated malignant phenotypes, including increased tumour mass and enhanced microvascular formation, leading to intracranial haemorrhage. These data demonstrate that, although mTORC1 hyperactivation itself may not be sufficient for gliomagenesis, it is a potent modifier of glioma development when combined with oncogenic signals.