A Novel Viscoelastic Deformation Mechanism Uncovered during Vickers Hardness Study of Bone.

This study investigates the viscoelastic deformation mechanisms of bone as a response to Vickers hardness indentation. We utilized advanced high-resolution scanning electron microscopy (SEM) to investigate a distinct deformation pattern that originates from the indentation site within the bone matrix. The focus of our research was to analyze a unique deformation mechanism observed in bone tissue, which has been colloquially termed as "screw-like" due to its resemblance to a screw thread when viewed under an optical microscope. The primary goals of this research are to investigate the distinctive characteristics of the "screw-like" deformation pattern and to determine how the microstructure of bone influences the initiation and control of this mechanism. These patterns, emerging during the dwell period of indentation, underscore the viscoelastic nature of bone, indicating its propensity for energy dissipation and microstructural reconfiguration under load. This study uncovered a direct correlation between the length of the "screw-like" deformation and the duration of the indentation dwell time, providing quantifiable evidence of the bone's viscoelastic behavior. This finding is pivotal in understanding the mechanical properties of bone, including its fracture toughness, as it relates to the complex interplay of factors such as energy dissipation, microstructural reinforcement, and stress distribution. Furthermore, this study discusses the implications of viscoelastic properties on the bone's ability to resist mechanical challenges, underscoring the significance of viscoelasticity in bone research.

Factores asociados al desarrollo de estenosis ureteral después de la ureteroscopia para cálculos ureterales impactados: estudio multicéntrico del grupo de trabajo de endourología y urolitiasis de la sección de Jóvenes Urólogos Académicos de la Asociación Europea de Urología / Factors associated with ureteral strictures following ureteroscopy for impacted ureteral stones. A multicenter study by EAU-YAU endourology and urolithiasis working party

Objetivo: Determinar la relación entre la impactación de los cálculos ureterales y la formación de estenosis ureterales y los factores asociados. Material y métodos Se analizaron retrospectivamente los registros médicos de todos los pacientes sometidos a cirugía endoscópica por cálculos ureterales impactados en 3 hospitales universitarios de Turquía, Reino Unido y España entre junio de 2019 y enero de 2022. Los parámetros examinados incluyeron los datos demográficos del paciente, lateralidad, tamaño y localización del cálculo, tiempo entre el inicio de los síntomas y la cirugía, tipo de ureteroscopia (rígida/flexible), presencia de nefrostomía o catéter doble J antes de la ureteroscopia, complicaciones intraoperatorias (avulsión/perforación), estado libre de cálculos, número de procedimientos necesarios para obtener un estado libre de cálculos y los resultados de las pruebas de imagen postoperatorias. Resultados Un total de 41 pacientes, 25 varones y 16 mujeres, de 3 instituciones fueron incluidos en el estudio. La edad media de los pacientes era de 48,2±13,5 años. La mediana del diámetro mayor de los cálculos fue de 9mm (RIC: 8mm). Catorce (34,1%) pacientes desarrollaron estenosis ureteral después de la ureteroscopia. No hubo diferencias entre los pacientes que desarrollaron estenosis ureteral y los que no la desarrollaron en cuanto a la lateralidad, la localización, la hidronefrosis y la multiplicidad de los cálculos (p=0,58, p=0,14, p=0,79 y p=0,31, respectivamente). Los pacientes que desarrollaron estenosis ureteral presentaron una tasa más elevada de derivación urinaria preoperatoria, como nefrostomía o catéter doble J (p=0,000). Conclusión La interrupción del paso de la orina por el uréter mediante derivación urinaria con nefrostomía o catéter doble J antes de la cirugía de cálculos ureterales podría favorecer la formación de estenosis ureteral en el postoperatorio. (AU)

Objective: To determine the relation between ureteral stone impaction and ureteral stricture formation and associated factors. Material and methods We retrospectively analyzed the medical records of all patients who underwent endoscopic ureteral stone surgery for impacted ureteral stone at 3 academic institutions in Turkey, United Kingdom and Spain between June 2019 and January 2022. Examined parameters included patient demographics, stone side, size and localization, time between initiation of symptoms and surgery, type of ureteroscopy (rigid/flexible), presence of nephrostomy or double-J stent prior to ureteroscopy, intraoperative complications (avulsion/perforation), stone-free status, number of procedures required for stone-free status, postoperative imaging results. Results A total of 41 patients whom 25 were male and 16 were female, from 3 institutions were included the study. The mean age of the patients was 48.2±13.5 years. The median largest diameter of the stones was 9mm (IQR: 8mm). Fourteen (34.1%) patients developed ureteral strictures following ureteroscopy. There was no difference between patients who developed ureteral strictures and patients who did not developed strictures in terms of stone laterality, stone location, hydronephrosis and multiplicity (p=0.58, p=0.14, p=0.79 and p=0.31, respectively). Patients who developed ureteral strictures had a higher rate of preoperative urinary diversion such as nephrostomy or double-J stent (p=0.000). Conclusion Interruption of urine passage through ureter via urinary diversion such as nephrostomy or double-J stent prior to ureteral stone surgery might lead ureteral stricture formation in the postoperative period. (AU)

Performance of the World Health Organisation suspected COVID-19 case definition in cluster-associated and sporadic SARS-CoV-2 transmission in Malaysia.

INTRODUCTION: Cluster-associated transmission has contributed to the majority of COVID-19 cases in Malaysia. Although widely used, the performance of the World Health Organization (WHO) case definition for suspected COVID19 in environments with high numbers of such cases has not been reported. MATERIALS AND METHODS: All suspected cases of COVID-19 that self-presented to hospitals or were cluster screened from 1st April to 31st May 2020 were included. Positive SARS-CoV-2 rRT-PCR was used as the diagnostic reference for COVID-19. RESULTS: 540 individuals with suspected COVID-19 were recruited. Two-third of patients were identified through contact screening, while the rest presented sporadically. Overall COVID-19 positivity rate was 59.4% (321/540) which was higher in the cluster screened group (85.6% vs. 11.6%, p<0.001). Overall, cluster-screened COVID-19 cases were significantly younger, had fewer comorbidities and were less likely to be symptomatic than those present sporadically. Mortality was significantly lower in the cluster-screened COVID-19 cases (0.3% vs. 4.5%, p<0.05). A third of all chest radiographs in confirmed COVID-19 cases were abnormal, with consolidation, ground-glass opacities or both predominating in the peripheral lower zones. The WHO suspected case definition for COVID-19 accurately classified 35.4% of all COVID-19 patients, a rate not improved by the addition of baseline radiographic data. Misclassification rate was higher among the cluster-associated cases (80.6%) compared to sporadic cases (35.3%). CONCLUSION: COVID-19 cases in Malaysia identified by active tracing of community cluster outbreaks had lower mortality rate. The WHO suspected COVID-19 performed poorly in this setting even when chest radiographic information was available, a finding that has implications for future spikes of the disease in countries with similar transmission characteristics.

Factors associated with ureteral strictures following ureteroscopy for impacted ureteral stones? A multicenter study by EAU-YAU endourology and urolithiasis working party.

OBJECTIVE: To determine the relation between ureteral stone impaction and ureteral stricture formation and associated factors. MATERIAL AND METHODS: We retrospectively analyzed the medical records of all patients who underwent endoscopic ureteral stone surgery for impacted ureteral stone at three academic institutions in Turkey, United Kingdom and Spain between June 2019 and January 2022. Examined parameters included patient demographics, stone side, size and localization, time between initiation of symptoms and surgery, type of ureteroscopy (rigid/flexible), presence of nephrostomy or double-J stent prior to URS, intraoperative complications (avulsion/perforation, stone-free status, number of procedures required for stone-free status, postoperative imaging results. RESULTS: A total of 41 patients whom 25 were male and 16 were female, from 3 institutions were included the study. The mean age of the patients was 48.2 ±â€¯13.5 years. The median largest diameter of the stones was 9 mm (IQR: 8 mm). Total 14 (34.1%) patients developed ureteral strictures following ureteroscopy. There was no difference between patients who developed ureteral strictures and patients who did not developed strictures in terms of stone laterality, stone location, hydronephrosis and multiplicity, p = 0.58, p = 0.14, p = 0.79 and p = 0.31. Patients who developed ureteral strictures had a higher rate of preoperative urinary diversion such as nephrostomy or DJS, p = 0.000. CONCLUSION: Interruption of urine passage through ureter via urinary diversion such as nephrostomy or DJS stent prior to ureteral stone surgery might lead ureteral stricture formation in the postoperative period.

Effect of heat treatment atmospheres on microstructure evolution and corrosion resistance of 2205 duplex stainless steel weldments.

The effects of post heat treatment atmosphere on microstructure and corrosion resistance of duplex stainless steel welded joints were investigated. Post weld heat treatment (PWHT) was carried out with and without protective atmospheres. Nitrogen and argon are used as protective gases individually. Detailed microstructure examination (optical and SEM) demonstrates that nitrides precipitates are highly observed in the welded zones for nitrogen protected samples. An observed drop of ferrite volume fraction in post weld heat treated samples compared with welded samples without heat treatment leading to corrosion resistance enhancement of heat treated welded joints. An exception for using nitrogen as heat treatment atmosphere a decreased corrosion resistance of weldments is investigated due to nitride precipitates. An increase in the weld zone hardness for post weld heat treated samples compared with base alloy. The initial hardness of duplex stainless steel was 286 Hv while average hardness of weld zone was 340, 411, 343, and 391 Hv for as welded, PWHT using air, argon, and nitrogen atmospheres, respectively. Weld zone hardness increased to 33, 44, 20, and 37%. A significant decrease in the ultimate tensile strength and elongation after PWHT. The initial Ultimate tensile strength duplex stainless steel base material was 734.9 MPa while Ultimate tensile strength of the welded joints was 769.3, 628.4, 737.8, and 681.4 MPa for the following conditions: as welded, PWHT using air, argon, and nitrogen atmospheres, respectively.

Glabratephrin reverses doxorubicin resistance in triple negative breast cancer by inhibiting P-glycoprotein.

Triple-negative breast cancer is one of the most aggressive breast cancer. The first therapeutic option is chemotherapy, often based on anthracycline as doxorubicin. However, chemotherapy efficacy is limited in by the presence of P-glycoprotein (Pgp), a membrane transporter protein that effluxes doxorubicin, reducing its cellular accumulation and toxicity. Inhibiting Pgp activity with effective and non-toxic products is still an open challenge. In this work, we demonstrated that the natural product Glabratephrin (Glab), a prenylated flavonoid from Tephrosia purpurea with a unique chemical structure, increased doxorubicin accumulation and cytotoxicity in triple negative breast cancer cells with high levels of Pgp, characterized by both acquired or intrinsic resistance to doxorubicin. Glab also reduced the growth of Pgp-expressing tumors, without adding significant extra-toxicities to doxorubicin treatment. Interestingly, Glab did not change the expression of Pgp, but it reduced the affinity for Pgp and the efflux of doxorubicin, as suggested by the increased Km and the reduced Vmax. In silico molecular docking predicted that Glab binds two residues (phenylalanine 322, glutamine 721) localized in the transmembrane domains of Pgp, facing the extracellular environment. Moreover, site-directed mutagenesis identified glycine 185 as a critical residue mediating the reduced catalytic efficacy of Pgp elicited by Glab. We propose Glab as an effective and safe compound able to reverse doxorubicin resistance mediated by Pgp in triple negative breast cancers, opening the way to a new combinatorial approach that may improve chemotherapy efficacy in the most refractory and aggressive breast cancer.

Synthesis of silver nanoparticle-decorated hydroxyapatite nanocomposite with combined bioactivity and antibacterial properties.

Combination of bioactive material such as hydroxyapatite (HAp) with antibacterial agents would have great potential to be used as bone implant materials to avert possible bacterial infection that can lead to implant-associated diseases. The present study aimed to develop an antibacterial silver nanoparticle-decorated hydroxyapatite (HAp/AgNPs) nanocomposite using chemical reduction and thermal calcination approaches. In this work, natural HAp that was extracted from chicken bone wastes is used as support matrix for the deposition of silver nanoparticles (AgNPs) to produce HAp/AgNPs nanocomposite. XRD, FESEM-EDX, HRTEM, and XPS analyses confirmed that spherical AgNPs were successfully synthesized and deposited on the surface of HAp particles, and the amount of AgNPs adhered on the HAp surface increased with increasing AgNO3 concentration used. The synthesized HAp/AgNPs nanocomposites demonstrated strong antibacterial activity against Staphylococcus aureus bacteria, where the antibacterial efficiency is relied on the amount and size of deposited AgNPs. In addition, the in vitro bioactivity examination in Hank's balanced salt solution showed that more apatite were grown on the surface of HAp/AgNPs nanocomposite when AgNO3 concentration used >1 wt.%. Such nanocomposite with enhanced bioactivity and antibacterial properties emerged as a promising biomaterial to be applied for dentistry and orthopedic implantology.

Time-based investigation of urinary metabolic markers for Type 2 diabetes: Metabolomics approach for diabetes management.

Diabetes is considered one of the most important health emergencies worldwide and Egypt has 8.2 million diabetic patients according to the International Diabetes Federation report in 2017. The objective of this study was to monitor the time-course variation in the metabolic profile of diabetic rats to detect urinary metabolic biomarkers using the metabolomics approach. Type 2 diabetes was induced in male Wistar albino rats using a single intraperitoneal injection of 40 mg/kg of streptozotocin following oral administration of 10% fructose in drinking water for 3 weeks. Then, urine was collected for 24 h from rats at three time points (0, 2, and 4 weeks after confirmation of diabetes), and were analyzed by nuclear magnetic resonance (H1 -NMR), followed by multivariate data analysis. The results from H1 -NMR pointed out that d-glucose, taurine, l-carnitine, l-fucose, 1,5-anhydrosorbitol, and d-galactose levels showed consistent significant variation (p < 0.05) between the positive (diabetic) and negative (normal) controls during the whole experimental period. Also, with the disease progression, myoinositol, and l-phenylalanine levels were significantly altered (p < 0.05) after 2 weeks and this alteration was maintained till the end of the 4-week experimental period in the positive control group. From the results of the present study, it could be concluded that we cannot depend only on glucose levels for prognostic purposes since there are other metabolic disturbances in diabetes which need to be tracked for better disease prognosis.

The Synergistic Cytotoxic and Apoptotic Effect of Resveratrol and Naringenin on Y79 Retinoblastoma Cell Line.

BACKGROUND: Resveratrol is a phenolic natural product, which is found in red grapes and in Japanese knotweed root (Polygonum cuspidatum). Naringenin is one of the flavonoid compounds found in landing grape and other citrus fruits. Both agents exert antioxidant and anti-inflammatory properties. OBJECTIVE: In this study, the effect of Resveratrol and Naringenin in an in vitro model of retinoblastoma of the eye has been investigated. METHODS: XTT and trypan blue assays were used to evaluate the anti-proliferative/cytotixic effect of resveratrol and naringenin in Y79 cells. With the aid of AnnexinV/PI flow cytometry, the kind of cell death was investigated. To assess important gene expression levels at mRNA level involved in apoptosis, Real-time PCR was utilized. RESULTS: Naringenin and resveratrol significantly decreased proliferation and stimulated cell death (mostly apoptosis) in Y79 cells at 50 and 100 (µg/ml) after 24 and 48 hours. Additional cytotoxic effect was observed after 48 hours. Furthermore expression level of Bax and Bcl2 mRNAs altered significantly in all samples treated with 50 (µg/ml) of naringenin, resveratrol, or simultaneously with both. P21 mRNAs expression altered in all mentioned samples except those treated with 50 (µg/ml) of resveratrol. CONCLUSION: Based on the results, it can be concluded that resveratrol and naringenin can decrease cell viability in retinoblastoma cells in an in vitro dose/time-dependent manner. Albeit more studies are needed to shed the light on the mechanism of action, our data reveal a potential synergistic cytotoxic effect of naringenin and resveratrol on Y79 cells in 48 hours.

Metabolomic profiling to reveal the therapeutic potency of Posidonia oceanica nanoparticles in diabetic rats.

Posidonia oceanica is a sea grass belonging to the family Posidoniaceae, which stands out as a substantial reservoir of bioactive compounds. In this study, the secondary metabolites of the P. oceanica rhizome were annotated using UPLC-HRESI-MS/MS, revealing 86 compounds including simple phenolic acids, flavonoids, and their sulphated conjugates. Moreover, the P. oceanica butanol extract exhibited substantial antioxidant and antidiabetic effects in vitro. Thus, a reliable, robust drug delivery system was developed through the encapsulation of P. oceanica extract in gelatin nanoparticles to protect active constituents, control their release and enhance their therapeutic activity. To confirm these achievements, untargeted GC-MS metabolomics analysis together with biochemical evaluation was employed to investigate the in vivo anti-diabetic potential of the P. oceanica nano-extract. The results of this study demonstrated that the P. oceanica gelatin nanoparticle formulation reduced the serum fasting blood glucose level significantly (p < 0.05) in addition to improving the insulin level, together with the elevation of glucose transporter 4 levels. Besides, multivariate/univariate analyses of the GC-MS metabolomic dataset revealed several dysregulated metabolites in diabetic rats, which were restored to normalized levels after treatment with the P. oceanica gelatin nanoparticle formulation. These metabolites mainly originate from the metabolism of amino acids, fatty acids and carbohydrates, indicating that this type of delivery was more effective than the plain extract in regulating these altered metabolic processes. Overall, this study provides novel insight for the potential of P. oceanica butanol extract encapsulated in gelatin nanoparticles as a promising and effective antidiabetic therapy.

Atorvastatin Prevents the Neuron Loss in the Hippocampal Dentate Gyrus Region through its Anti-Oxidant and Anti-Apoptotic Activities.

BACKGROUND: Atorvastatin is a member of statins, which has shown positive vascular effects, anti-oxidant, anti-platelet, and anti-apoptotic properties. OBJECTIVE: In this study, we hypothesized that atorvastatin could prevent the neurons lost in the hippocampal dentate gyrus region after transient global Ischemia/Reperfusion (I/R) through its anti- oxidant and anti-apoptotic activities. METHOD: Twenty-four male Wistar rats, 12-13 weeks old and weighing 250-300 g, were divided randomly into four groups: control, I/R, vehicle (I/R treated with NaCl) and experiment (I/R treated with atorvastatin, 10 mg/kg); rats were sacrificed 96 hours after I/R. Quantitative expression of genes (caspase 8, p53, bax, bcl2, cytochrome c) was studied. The MDA level, SOD, CAT, and GPx activities were measured with biochemical tests. To detect apoptotic cells, TUNEL and Nissl staining were performed. Mitochondria were prepared from the hippocampus rats and used for the quantification of mitochondrial ROS, ATP level, GSH content, membrane potential, cytochrome c release, and determination of mitochondrial swelling. RESULTS: Atorvastatin attenuated the overexpression of bax, cytochrome C, p53, and caspase8 mRNAs and induced expression of bcl-2 mRNA (P<0.001). Atorvastatin treatment increased anti-oxidant enzyme levels (P<0.01). Treatment with atorvastatin reduced the number of TUNEL-positive cells. It could decrease the cytochrome c release (P<0.01), inhibit the decrease of MMP (P<0.001) and increase the ATP level (P<0.001) in hippocampal mitochondria compared with the I/R group. CONCLUSION: Atorvastatin treatment in I/R rats decreases oxidative stress, production of ROS, apoptosis rate in neuronal cells, and improves the mitochondrial function. Hence, atorvastatin has a proper neuronal protective effect against the I/R injury in the brain.

Hardness, an Important Indicator of Bone Quality, and the Role of Collagen in Bone Hardness.

Bone is a nanocomposite material where the hard inorganic (hydroxyapatite crystallites) and organic (collagen fibrils) components are hierarchically arranged in the nanometer scale. Bone quality is dependent on the spatial distributions in the shape, size and composition of bone constituents (mineral, collagen and water). Bone hardness is an important property of bone, which includes both elastic and plastic deformation. In this study, a microhardness test was performed on a deer bone samples. The deer tibia shaft (diaphysis) was divided into several cross-sections of equal thickness; samples were prepared in untreated, boiled water treatment (100 °C for 30 min) and sodium hypochlorite (NaOCl) treatment conditions. Microhardness tests were performed on various regions of the tibial diaphysis to study the heterogeneous characteristics of bone microhardness and highlight the role of the organic matrix in bone hardness. The results indicated that boiled water treatment has a strong negative correlation with bone hardness. The untreated bone was significantly (+20%) harder than the boiled-water-treated bone. In general, the hardness values near the periosteal surface was significantly (23 to 45%) higher than the ones near the endosteal surface. Samples treated with NaOCl showed a significant reduction in hardness.

Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy.

Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI3K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in hepatocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy.

Lymphoma with superimposed tuberculosis and fungal infection mimicking parapharyngeal abscess complicated with recurrent neurocardiogenic syncope: a case report.

INTRODUCTION: Lymphoma of parapharyngeal space (PPS) is a rare condition. The clinical presentations may vary and often masquerades as infection or an inflammatory condition. A misdiagnosis will lead to a delay in treatment of the disease. Due to the complex anatomy of PPS, any attributed pressure from masses can lead to a life-threatening event such as cardiac syncope. CASE REPORT: We report a rare case of PPS B-cell non-Hodgkin lymphoma with superimposed Tuberculosis (TB) and fungal infection that presents with several episodes of syncope and hemodynamic depression. DISCUSSION: The clinical entities in PPS lesions syncope and its associated syndromes, pathophysiology, and differential diagnosis together with possible managements are further discussed.

Hyssopus officinalis exerts hypoglycemic effects on streptozotocin-induced diabetic rats via modulating GSK-3ß, C-fos, NF-κB, ABCA1 and ABGA1 gene expression.

OBJECTIVES: Type 2 diabetes mellitus (DMT2) is contributed to dual interactions between environmental factors and certain genetic factors. This impressed a great need for novel treatment strategy. Nevertheless, Hyssopus officinalis (H. officinalis) as a terrestrial herb is considered to be an important source of natural antioxidants, it could be assessed as an anti-hyperglycemic agent. METHODS: In the current study, HPLC identified the active constitutes of H. officinalis, including total polyphenols, and flavonoids. Type 2 diabetes mellitus was induced in male Wistar albino rats via a single ip dose of streptozotocin (STZ) (35 mg/kg BW). One week post diabetes induction, rats were administrated H. officinalis (500 mg/ kg BW) orally for one month. Molecular analysis was assessed to investigate the efficiency of H. officinalis on modulating ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) genes, in addition to apoptotic biomarkers, glycogen synthase kinase-3ß (GSK-3ß) and cellular oncogene-fos (C-fos) genes. Furthermore, inflammatory biomarkers, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) gene expression were also assessed. RESULTS: H. officinalis alcoholic extract declared the presence of polyphenols as gallic acid and flavonoids as quercetin in addition to many active constituents. Apigenin-7-glucoside and Chlorgenic acid were the most common constituents in the extract. RT-PCR results declared a significant up-regulation in mRNA gene expression of ABCA1 and ABCG1 upon H. officinalis treatment. Meanwhile, C-fos gene expression recorded a slight down-regulation. Gene expression of apoptotic biomarker GSK-3ß demonstrated a significant down regulation as well as inflammatory biomarkers NF-κB and TNF-α. CONCLUSION: From the data recorded, it could be concluded that H. officinalis exerts a great hypoglycemic potential via modulating C-fos, GSK-3ß, NF-κB, TNF-α, ABCA1 and ABCG1 gene expression and signaling pathways and could be considered as an effective candidate for DMT2 treatment.

Osteoblasts migration, attachment and human bone marrow-mesenchymal stem cells osteogenic differentiation towards surface engineered and growth factors conjugated poly(lactic acid) microspheres.

Recently, surface engineered biomaterials through surface modification are extensively investigated due to its potential to enhance cellular homing and migration which contributes to a successful drug delivery process. This study is focused on osteoblasts response towards surface engineered using a simple sodium hydroxide (NaOH) hydrolysis and growth factors conjugated poly(lactic acid) (PLA) microspheres. In this study, evaluation of the relationship of NaOH concentration with the molecular weight changes and surface morphology of PLA microspheres specifically wall thickness and porosity prior to in vitro studies was investigated. NaOH hydrolysis of 0.1 M, 0.3 M and 0.5 M were done to introduce hydrophilicity on the PLA prior to conjugation with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Morphology changes showed that higher concentration of NaOH could accelerate the hydrolysis process as the highest wall thickness was observed at 0.5 M NaOH with ~3.52 µm. All surface modified and growth factors conjugated PLA microspheres wells enhanced the migration of the cells during wound healing process as wound closure was 100% after 3 days of treatment. Increase in hydrophilicity of the surface engineered and growth factors conjugated PLA microspheres provides favorable surface for cellular attachment of osteoblast, which was reflected by positive DAPI staining of the cells' nucleus. Surface modified and growth factors conjugated PLA microspheres were also able to enhance the capability of the PLA in facilitating the differentiation process of mesenchymal stem cells (MSCs) into osteogenic lineage since only positive stain was observed on surface engineered and growth factors conjugated PLA microspheres. These results indicated that the surface engineered and growth factors conjugated PLA microspheres were non-toxic for biological environments and the improved hydrophilicity made them a potential candidate as a drug delivery vehicle as the cells can adhere, attach and proliferate inside it.

Cyanidin 3-O-Glucoside Induces the Apoptosis in the Osteosarcoma Cells through Upregulation of the PPARγ and P21: An In Vitro Study.

BACKGROUND: Osteosarcoma (OS) is known as the malignant tumors in the bone. Cyanidin 3-OGlucoside (C3G) has a potential to induce the apoptotic cell death in different cancer cells; however, the mechanisms of action for C3G have not been clarified yet. OBJECTIVE: In this study, the apoptotic effects of C3G on three different osteosarcoma cell lines including Saso-2, MG-63, and G-292 (clone A141B1) were investigated. METHODOLOGY: The 24-hr IC50 of C3G for Saso-2, G-292, and MG-63 cells was evaluated by the MTT assay. Apoptosis induction in these cell lines after treatment with the C3G was approved by the Annexin V/PI flow cytometry. Changes at the mRNA expression level of PPARγ, P21, Bax, and Bcl-xl genes were investigated by real-time Polymerase Chain Reaction (PCR) technique, and P21 expression was further confirmed by the western blotting. RESULTS: The MTT assay results demonstrated that the 24-hr IC50 of C3G was equal to 110µg/ml for Saso-2 and G-292 cells while it was about 140µg/ml for the MG-63 cells. The results of real-time PCR clearly showed that treatment of the cells with 24hrs IC50 of C3G caused the upregulation of PPARγ, P21, and Bax genes. Moreover, western blot analysis confirmed that P21 protein overexpressed endogenously after treatment of the cells with the C3G, and it was more upregulated in the MG-63 cells compared to the other cell lines. CONCLUSION: According to the findings of the study, the C3G is a novel anti-osteosarcoma agent with the ability to induce the apoptosis in different osteosarcoma cells through upregulation of the PPARγ and P21 genes.

Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche.

Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.

Assessment of titanium dioxide nanoparticles toxicity via oral exposure in mice: effect of dose and particle size.

Objective: The aim of the present work is to evaluate the toxicity of titanium dioxide nanoparticles (TiO2NPs) according to their doses and particle sizes. Materials and methods: The effect of five days oral administration of TiO2NPs (21 and 80 nm) with different doses (50, 250 and 500 mg/kg body weight) was assessed in mice via measurement of oxidative stress markers; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO), liver function indices; aspartate and alanine aminotransferases (AST and ALT), chromosomal aberrations and liver histopathological pattern. Results: The results revealed drastic alterations in all the measured parameters and showed positive correlation with the gradual dose increment. In addition, the smaller particle size of TiO2NPS (21 nm) had more adverse effect in all the selected biochemical parameters, genetic aberrations and histological investigations. Conclusions: Toxicity of TiO2NPs increases in a dose-dependent manner and vice versa with particles size. The evaluated biomarkers are good indicators for TiO2NPs toxicity. More detailed studies are required before the recommendation of TiO2NPS as food additives.