Dr.Muhammad Samman | King Saud University (original) (raw)

Papers by Dr.Muhammad Samman

Research paper thumbnail of Comparative Evaluation of Microleakage and Shear Bond Strength of Bioactive Dentin Substitute and Nanohybrid Composite Resin

Egyptian Dental Journal, 2018

Background: In clinical practice, the restoration of non-carious cervical lesions is a challenge,... more Background: In clinical practice, the restoration of non-carious cervical lesions is a challenge, because most of the time the cervical margin is located in cementum or dentin. This characteristic makes the cervical margin more susceptible to microleakage, causing marginal stains, postoperative sensitivity and recurrent caries. Aim: To compare the microleakage and bond strength for teeth restored with Activa Bioactive restorative and nanohybrid composite resin Materials and methods: Twenty permanent premolars were selected with class V cavities for microleakage, and 20 permanent premolars were selected for shear bond strength. Microleakage was checked using dye penetration method under digital microscope Universal testing device was used to assess the shear bond strength. Leakage scores, mean and standard deviation values for shear bond strength were calculated from the recorded values. For numerical data student t-test was performed to detect the significance between both groups. For categorical data analysis Chi square test was done. Results; There was non-significant difference between ACTIVA bioactive restorative group and nanohybrid composite resin group in both parameters; leakage and bond strength Conclusion: Based on the results of the present study, the type of restorative material did not appear to have a significant influence on microleakage or bond strength

Research paper thumbnail of The Effect of Antioxidants on the Bond Strength of Resin Composite to Bleached Enamel

Egyptian Dental Journal, 2017

Aim : This study aimed to assess the effect of treating bleached enamel with antioxidants on the ... more Aim : This study aimed to assess the effect of treating bleached enamel with antioxidants on the value of shear bond strength of resin composite to enamel. Also, a comparison was set between the natural antioxidant used (5% pomegranate solution) and the chemical one (10 % sodium ascorbate gel). Materials and Methods: Fifty six human freshly extracted sound upper anterior teeth were used. The specimens were randomly divided into four main groups as follow : Group I : control(no bleaching) ; Group II : bleached then treated with the chemical antioxidant ; Group III : bleached then treated with the natural antioxidant; Group IV : bleached with no antioxidant treatment. Each group was further subdivided into two subgroups according to whether the restoration was performed immediately or delayed (after one month incubation in artificial saliva) (n=7). The variables were as follow: No bleaching immediate restoration (control) ; no bleaching delayed restoration after incubation for one month in artificial saliva ; bleached followed by application of a chemical antioxidant (10% sodium ascorbate gel) for 10 min then immediate restoration;bleached followed by application of a chemical antioxidant (10% sodium ascorbate gel) for 10 min then delayed restoration; bleached followed by application of a natural antioxidant (5% pome granate solution) for 10 min then immediate restoration ; bleached followed by application of a natural antioxidant (5% pome granate solution) for 10 min then delayed restoration ; bleached with no application of an antioxidant then immediate restoration ; bleached with no application of an antioxidant then delayed restoration. The data were statistically analyzed using two way ANOVA test, one way ANOVA test, Tuckey's post-hoc tests and pair wise student T-test. Results : Regarding the mean shear bond strength values (immediate restoration) ; the control subgroup (immediately restored) demonstrated the highest values followed by the bleached subgroups treated with the natural antioxidant (5% pomegranate solution), then the bleached subgroups treated with the chemical antioxidant (10% sodium ascorbate gel). The bleached subgroups that were not treated with the antioxidants showed the least values. Regarding the subgroups that undergone a delayed investigation ; the subgroups treated with the natural antioxidant demonstrated the highest shear bond strength values followed by the subgroups treated with chemical antioxidants then the control group while the bleached subgroups that were not treated with the antioxidants showed the least values of mean shear bond strength

Research paper thumbnail of The Effect of Egg Shell Versus Fluoride Varnish on Remineralization of Early Enamel Demineralized Lesions

Egyptian Dental Journal, 2017

Twenty freshly extracted non-carious human molars were used. The mineral content of all teeth was... more Twenty freshly extracted non-carious human molars were used. The mineral content of all teeth was initially assessed using EDX. Teeth were then divided randomly into two groups each containing ten samples. All teeth were placed in demineralizing agent after which one group (I) was remineralized using egg shell solution while the other group (II) was remineralized using fluoride varnish (Proshield, President dental Germany). This process was held in a pH cycling mode.Regarding mineral content specimens of both groups were initially assessed (base line measurements), then reassessed directly after demineralization, three days from remineralization and at the end of seven days remineralization period. Results were as follow : Regarding Ca wt % and comparing the two groups there was no statistical significance at base line measurements, after demineralization and after three days from remineralization. Meanwhile after seven days remineralization group (I) demonstrated statistically significant lower mean Ca atomic wt % than group (II). Regarding phosphorus atomic wt % for measurements of base line, after demineralization and after remineralization there was no statistical significance between the two groups. Regarding the effect of time for Ca wt % and after seven days group (I) showed non statistically significant decrease in Ca wt % compared to that at base line, while group (II) showed non statistically significant difference from the value measured at base line. For the P wt % and after seven days both groups demonstrated non statistically significant lower mean values compared to base line data.

Research paper thumbnail of Bond Strength of Bulk-Fill Composite Resins to Dentin with Different Adhesion Approaches

Egyptian Dental Journal, 2017

Background and aim; Bulk fill resin composites have been proven in several studies to enable rest... more Background and aim; Bulk fill resin composites have been proven in several studies to enable restoration in thick layers, up to 4mm, maintaining the mechanical properties and the degree of conversion within the whole increment. This study was designed to evaluate micro tensile bond strength (µTBS) of bulk-fill composite resins to superficial and deep dentin with different adhesion approaches. Materials and methods; Extracted human premolar teeth (n=24) were used to prepare 120 resin-dentin sticks. Specimens were divided into two main groups according to the type of bulk-fill composite used (Xtra fill & Tetric-N-Ceram). Each main group was subdivided according to the adhesive approach used into (total & self-etch). According to dentin depths each subgroup was further categorized into (superficial and deep). µTBS was evaluated using universal testing machine at a crosshead speed of 0.5 mm/min. Dentin / resin interfaces were assessed by scanning electron microscopy. Results; The results showed significant (p<0.05) effect of composite and dentin level on µTBS, while the effect of adhesive approach was non-significant (p>0.05). Conclusion; Xtra-Fill has higher µTBS than Tetric Bulk-fill. Total-etch adhesive system has higher µTBS than self-etch with the superficial dentin. Self-etch adhesive system has higher µTBS than total etch with the deep dentin.

Research paper thumbnail of Bonding Ability of Different Liners to Bulk-Fill Resin Composite Using Silane-Containing Adhesive

Egyptian Dental Journal, 2017

Aims: To compare and evaluate the bonding ability of bulk-fill resin composite (RC) to four diffe... more Aims: To compare and evaluate the bonding ability of bulk-fill resin composite (RC) to four different liners: Biodentine (BD), TheraCal (TLC)-a novel resin-modified calcium silicate cement, resin-modified glass ionomer cement (RMGIC) and conventional glass ionomer cement (GIC) using a universal silane-containing adhesive and characterizing their failure modes. Materials and Methods: Forty extracted intact human premolars with occlusal cavity (4-mm diameter and 2-mm height) were mounted in acrylic blocks and divided into four groups of (n=10 samples) each based on the liner used as group I; (BD), group II; (TLC), group III; (RMGIC) and Group IV; (GIC). Bulk-fill composite buildup of 3 mm diameter and 5 mm height was then bonded to each sample using universal adhesive. Shear bond strength (SBS) analysis was performed using materials testing machine at a cross-head speed of 0.5 mm/min. Statistical Analysis: Statistical analysis was performed with one-way analysis of variance (ANOVA) and Tukey's post hoc test for numerical data while chi square test for categorical one. Results: One-way analysis with ANOVA revealed significant difference in bond strength values between the different groups (p<0.001). The observed modes of failure were predominantly cohesive in Biodentine, TheraCal and GIC groups while RMGIC showed majority of mixed and minority adhesive failures. Conclusions: Biodentine demonstrated lower bond strength values when immediately bonded to bulk-fill resin composite compared with RMGIC, TheraCal and GIC groups (2906)

Research paper thumbnail of Evaluation of two-body wear rate and roughness of polyetheretherketone and zirconia opposing enamel structure: an in-vitro study

Journal of The Arab Society for Medical Research, 2019

Background/aim Investigation of polyetheretherketone (PEEK), a new synthetic thermoplastic polyme... more Background/aim Investigation of polyetheretherketone (PEEK), a new synthetic thermoplastic polymer, as an alternative for zirconia for veneering frameworks, to be used with weakened abutment teeth, as in cases of patients with parafunctional habits. This study aimed to investigate the two-body wear rate and roughness of PEEK and zirconia by itself and against human enamel. Materials and methods A total of six disc-shaped zirconia (n=6) and six disc-shaped PEEK specimens (n=6) (10 mm in diameter with a thickness of 2 mm) were prepared. Human enamel antagonists were produced by sectioning of 12 premolars. The two-body wear testing was performed using chewing simulator. Weight loss was assessed by electronic analytical balance. The optical profilometry was used for roughness evaluation. Results The findings of this study revealed that PEEK showed a comparable effect upon comparison with zirconia, although there was a statistically nonsignificant difference between weight changes recorded for wear in both PEEK and zirconia groups, tested alone or with enamel antagonists, as indicated by the unpaired t test. Moreover, the optical profilometer revealed that, the difference between surface roughness changes recorded for both groups, tested alone or with enamel antagonists, was statistically nonsignificant as indicated by the unpaired t test. Conclusion PEEK showed a promising effect in terms of antagonistic tooth wear and roughness upon comparison with zirconia. However, the results were not significant between both materials.

Research paper thumbnail of Epigenetics of human diseases and scope in future therapeutics

Journal of Taibah University Medical Sciences, 2017

Research paper thumbnail of CXCR3 Ligands induce Expression of CXCL1 (KC/murine IL8 homolog) in Mouse Hepatic Stellate Cells

Journal of Cell Science & Therapy, 2012

Background and aim: Liver injury leads to infiltration of immune cells and a subsequent activatio... more Background and aim: Liver injury leads to infiltration of immune cells and a subsequent activation of hepatic stellate cells. Chemokines are ubiquitous chemotactic proteins which are involved in inflammatory pathways. It has been recently suggested that chemokines can also induce the expression of other chemokines and thereby indirectly regulate immune cell recruitment. We therefore investigated the ability of the chemokine CXCL9 to induce CXCL1, an important neutrophil chemoattractant. Methods: The ability of CXCR3 ligands CXCL9 and CXCL10 to induce CXCL1 expresssion was analyzed in immortalized (GRX) and primary hepatic stellate cells isolated from wild-type and CXCR3-/mice. Cells were treated with different concentrations of chemokines in the absence and presence of pertussis toxin. Furthermore, mice were treated systemically with CXCL9 and hepatic CXCL1 levels as well as neutrophil infiltration were assessed. Results: Treatment of GRX cells with CXCL9 leads to a dose dependent induction of CXCL1 protein expression. This stimulatory effect was validated in primary hepatic stellate cells (P<0.01). In contrast, stimulation of stellate cells with CCL2 did not result in CXCL1 induction. Increased CXCL1 expression in response to CXCL9 was completely abolished by co-incubation with pertussis toxin and in stellate cells derived from CXCR3-/mice, the canonical receptor for CXCL9 and CXCL10. Notably, systemic treatment of mice with CXCL9 led to elevated hepatic CXCL1 levels and was associated with enhanced neutrophil infiltration into the liver. Conclusions: The study describes a chemokine-chemokine pathway in hepatic stellate cells which leads to augmented infiltration of neutrophils into the liver during acute liver injury.

Research paper thumbnail of Proteomic Profiling of Secreted Proteins for the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells

Cell Transplantation, 2013

Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly imp... more Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the most comprehensive proteomic profiling of the HUVEC secretome and identified 827 different secreted proteins. Two hundred and thirty-one proteins were found in all conditions, whereas 369 proteins were identified only under proinflammatory conditions following IL-1β, IL-3, and IL-6 stimulation. Thirteen proteins including complement factor b (CFb) were identified only under IL-1β and IL-3 conditions and may potentially represent HSPC proliferation factors. The combination of bioinformatics and gene ontology annotations indicates the role of the complement system and its activation. Furthermore, CFb was found to be transcriptionally strongly upregulated. Addition of complement component 5b-9 (C5b-9) monoclonal antibody to the stem cell ...

Research paper thumbnail of Homozygous sequence variants in the FKBP10 gene underlie osteogenesis imperfecta in consanguineous families

Journal of Human Genetics, 2015

Osteogenesis imperfecta (OI, MIM 610968) is a genetically and clinically heterogeneous disorder c... more Osteogenesis imperfecta (OI, MIM 610968) is a genetically and clinically heterogeneous disorder characterized by bone fragility. It is one of the rare forms of skeletal deformity caused by sequence variants in at least 14 different genes, including FKBP10 (MIM 607063) encoding protein FKBP65. Here we present three consanguineous families of Pakistani origin segregating OI in an autosomal-recessive pattern. Genotyping using either single-nucleotide polymorphism markers by Affymetrix GeneChip Human Mapping 250K Nsp array or polymorphic microsatellite markers revealed a homozygous region, containing a candidate gene FKBP10, among affected members on chromosome 17q21.2. Sequencing the FKBP10 gene revealed a homozygous novel nonsense variant (c.1490G4A, p.Trp497*) in the family A and two previously reported variants, including a missense (c.344G4A, p.Arg115Gln), in the family B and duplication of a nucleotide C (c.831dupC, p.Gly278ArgfsX295) in the family C. Our findings further extend the body of evidence that supports the importance of FKBP10 gene in the development of skeletal system.

Research paper thumbnail of Chemokine Cxcl9 attenuates liver fibrosis-associated angiogenesis in mice

Hepatology (Baltimore, Md.), 2012

Recent data suggest that the chemokine receptor CXCR3 is functionally involved in fibroproliferat... more Recent data suggest that the chemokine receptor CXCR3 is functionally involved in fibroproliferative disorders, including liver fibrosis. Neoangiogenesis is an important pathophysiological feature of liver scarring, but a functional role of angiostatic CXCR3 chemokines in this process is unclear. We therefore investigated neoangiogenesis in carbon tetrachloride (CCl(4))-induced liver fibrosis in Cxcr3(-/-) and wildtype mice by histological, molecular, and functional imaging methods. Furthermore, we assessed the direct role of vascular endothelial growth factor (VEGF) overexpression on liver angiogenesis and the fibroproliferative response using a Tet-inducible bitransgenic mouse model. The feasibility of attenuation of angiogenesis and associated liver fibrosis by therapeutic treatment with the angiostatic chemokine Cxcl9 was systematically analyzed in vitro and in vivo. The results demonstrate that fibrosis progression in Cxcr3(-/-) mice was strongly linked to enhanced neoangiogene...

Research paper thumbnail of Comparative Evaluation of Microleakage and Shear Bond Strength of Bioactive Dentin Substitute and Nanohybrid Composite Resin

Egyptian Dental Journal, 2018

Background: In clinical practice, the restoration of non-carious cervical lesions is a challenge,... more Background: In clinical practice, the restoration of non-carious cervical lesions is a challenge, because most of the time the cervical margin is located in cementum or dentin. This characteristic makes the cervical margin more susceptible to microleakage, causing marginal stains, postoperative sensitivity and recurrent caries. Aim: To compare the microleakage and bond strength for teeth restored with Activa Bioactive restorative and nanohybrid composite resin Materials and methods: Twenty permanent premolars were selected with class V cavities for microleakage, and 20 permanent premolars were selected for shear bond strength. Microleakage was checked using dye penetration method under digital microscope Universal testing device was used to assess the shear bond strength. Leakage scores, mean and standard deviation values for shear bond strength were calculated from the recorded values. For numerical data student t-test was performed to detect the significance between both groups. For categorical data analysis Chi square test was done. Results; There was non-significant difference between ACTIVA bioactive restorative group and nanohybrid composite resin group in both parameters; leakage and bond strength Conclusion: Based on the results of the present study, the type of restorative material did not appear to have a significant influence on microleakage or bond strength

Research paper thumbnail of The Effect of Antioxidants on the Bond Strength of Resin Composite to Bleached Enamel

Egyptian Dental Journal, 2017

Aim : This study aimed to assess the effect of treating bleached enamel with antioxidants on the ... more Aim : This study aimed to assess the effect of treating bleached enamel with antioxidants on the value of shear bond strength of resin composite to enamel. Also, a comparison was set between the natural antioxidant used (5% pomegranate solution) and the chemical one (10 % sodium ascorbate gel). Materials and Methods: Fifty six human freshly extracted sound upper anterior teeth were used. The specimens were randomly divided into four main groups as follow : Group I : control(no bleaching) ; Group II : bleached then treated with the chemical antioxidant ; Group III : bleached then treated with the natural antioxidant; Group IV : bleached with no antioxidant treatment. Each group was further subdivided into two subgroups according to whether the restoration was performed immediately or delayed (after one month incubation in artificial saliva) (n=7). The variables were as follow: No bleaching immediate restoration (control) ; no bleaching delayed restoration after incubation for one month in artificial saliva ; bleached followed by application of a chemical antioxidant (10% sodium ascorbate gel) for 10 min then immediate restoration;bleached followed by application of a chemical antioxidant (10% sodium ascorbate gel) for 10 min then delayed restoration; bleached followed by application of a natural antioxidant (5% pome granate solution) for 10 min then immediate restoration ; bleached followed by application of a natural antioxidant (5% pome granate solution) for 10 min then delayed restoration ; bleached with no application of an antioxidant then immediate restoration ; bleached with no application of an antioxidant then delayed restoration. The data were statistically analyzed using two way ANOVA test, one way ANOVA test, Tuckey's post-hoc tests and pair wise student T-test. Results : Regarding the mean shear bond strength values (immediate restoration) ; the control subgroup (immediately restored) demonstrated the highest values followed by the bleached subgroups treated with the natural antioxidant (5% pomegranate solution), then the bleached subgroups treated with the chemical antioxidant (10% sodium ascorbate gel). The bleached subgroups that were not treated with the antioxidants showed the least values. Regarding the subgroups that undergone a delayed investigation ; the subgroups treated with the natural antioxidant demonstrated the highest shear bond strength values followed by the subgroups treated with chemical antioxidants then the control group while the bleached subgroups that were not treated with the antioxidants showed the least values of mean shear bond strength

Research paper thumbnail of The Effect of Egg Shell Versus Fluoride Varnish on Remineralization of Early Enamel Demineralized Lesions

Egyptian Dental Journal, 2017

Twenty freshly extracted non-carious human molars were used. The mineral content of all teeth was... more Twenty freshly extracted non-carious human molars were used. The mineral content of all teeth was initially assessed using EDX. Teeth were then divided randomly into two groups each containing ten samples. All teeth were placed in demineralizing agent after which one group (I) was remineralized using egg shell solution while the other group (II) was remineralized using fluoride varnish (Proshield, President dental Germany). This process was held in a pH cycling mode.Regarding mineral content specimens of both groups were initially assessed (base line measurements), then reassessed directly after demineralization, three days from remineralization and at the end of seven days remineralization period. Results were as follow : Regarding Ca wt % and comparing the two groups there was no statistical significance at base line measurements, after demineralization and after three days from remineralization. Meanwhile after seven days remineralization group (I) demonstrated statistically significant lower mean Ca atomic wt % than group (II). Regarding phosphorus atomic wt % for measurements of base line, after demineralization and after remineralization there was no statistical significance between the two groups. Regarding the effect of time for Ca wt % and after seven days group (I) showed non statistically significant decrease in Ca wt % compared to that at base line, while group (II) showed non statistically significant difference from the value measured at base line. For the P wt % and after seven days both groups demonstrated non statistically significant lower mean values compared to base line data.

Research paper thumbnail of Bond Strength of Bulk-Fill Composite Resins to Dentin with Different Adhesion Approaches

Egyptian Dental Journal, 2017

Background and aim; Bulk fill resin composites have been proven in several studies to enable rest... more Background and aim; Bulk fill resin composites have been proven in several studies to enable restoration in thick layers, up to 4mm, maintaining the mechanical properties and the degree of conversion within the whole increment. This study was designed to evaluate micro tensile bond strength (µTBS) of bulk-fill composite resins to superficial and deep dentin with different adhesion approaches. Materials and methods; Extracted human premolar teeth (n=24) were used to prepare 120 resin-dentin sticks. Specimens were divided into two main groups according to the type of bulk-fill composite used (Xtra fill & Tetric-N-Ceram). Each main group was subdivided according to the adhesive approach used into (total & self-etch). According to dentin depths each subgroup was further categorized into (superficial and deep). µTBS was evaluated using universal testing machine at a crosshead speed of 0.5 mm/min. Dentin / resin interfaces were assessed by scanning electron microscopy. Results; The results showed significant (p<0.05) effect of composite and dentin level on µTBS, while the effect of adhesive approach was non-significant (p>0.05). Conclusion; Xtra-Fill has higher µTBS than Tetric Bulk-fill. Total-etch adhesive system has higher µTBS than self-etch with the superficial dentin. Self-etch adhesive system has higher µTBS than total etch with the deep dentin.

Research paper thumbnail of Bonding Ability of Different Liners to Bulk-Fill Resin Composite Using Silane-Containing Adhesive

Egyptian Dental Journal, 2017

Aims: To compare and evaluate the bonding ability of bulk-fill resin composite (RC) to four diffe... more Aims: To compare and evaluate the bonding ability of bulk-fill resin composite (RC) to four different liners: Biodentine (BD), TheraCal (TLC)-a novel resin-modified calcium silicate cement, resin-modified glass ionomer cement (RMGIC) and conventional glass ionomer cement (GIC) using a universal silane-containing adhesive and characterizing their failure modes. Materials and Methods: Forty extracted intact human premolars with occlusal cavity (4-mm diameter and 2-mm height) were mounted in acrylic blocks and divided into four groups of (n=10 samples) each based on the liner used as group I; (BD), group II; (TLC), group III; (RMGIC) and Group IV; (GIC). Bulk-fill composite buildup of 3 mm diameter and 5 mm height was then bonded to each sample using universal adhesive. Shear bond strength (SBS) analysis was performed using materials testing machine at a cross-head speed of 0.5 mm/min. Statistical Analysis: Statistical analysis was performed with one-way analysis of variance (ANOVA) and Tukey's post hoc test for numerical data while chi square test for categorical one. Results: One-way analysis with ANOVA revealed significant difference in bond strength values between the different groups (p<0.001). The observed modes of failure were predominantly cohesive in Biodentine, TheraCal and GIC groups while RMGIC showed majority of mixed and minority adhesive failures. Conclusions: Biodentine demonstrated lower bond strength values when immediately bonded to bulk-fill resin composite compared with RMGIC, TheraCal and GIC groups (2906)

Research paper thumbnail of Evaluation of two-body wear rate and roughness of polyetheretherketone and zirconia opposing enamel structure: an in-vitro study

Journal of The Arab Society for Medical Research, 2019

Background/aim Investigation of polyetheretherketone (PEEK), a new synthetic thermoplastic polyme... more Background/aim Investigation of polyetheretherketone (PEEK), a new synthetic thermoplastic polymer, as an alternative for zirconia for veneering frameworks, to be used with weakened abutment teeth, as in cases of patients with parafunctional habits. This study aimed to investigate the two-body wear rate and roughness of PEEK and zirconia by itself and against human enamel. Materials and methods A total of six disc-shaped zirconia (n=6) and six disc-shaped PEEK specimens (n=6) (10 mm in diameter with a thickness of 2 mm) were prepared. Human enamel antagonists were produced by sectioning of 12 premolars. The two-body wear testing was performed using chewing simulator. Weight loss was assessed by electronic analytical balance. The optical profilometry was used for roughness evaluation. Results The findings of this study revealed that PEEK showed a comparable effect upon comparison with zirconia, although there was a statistically nonsignificant difference between weight changes recorded for wear in both PEEK and zirconia groups, tested alone or with enamel antagonists, as indicated by the unpaired t test. Moreover, the optical profilometer revealed that, the difference between surface roughness changes recorded for both groups, tested alone or with enamel antagonists, was statistically nonsignificant as indicated by the unpaired t test. Conclusion PEEK showed a promising effect in terms of antagonistic tooth wear and roughness upon comparison with zirconia. However, the results were not significant between both materials.

Research paper thumbnail of Epigenetics of human diseases and scope in future therapeutics

Journal of Taibah University Medical Sciences, 2017

Research paper thumbnail of CXCR3 Ligands induce Expression of CXCL1 (KC/murine IL8 homolog) in Mouse Hepatic Stellate Cells

Journal of Cell Science & Therapy, 2012

Background and aim: Liver injury leads to infiltration of immune cells and a subsequent activatio... more Background and aim: Liver injury leads to infiltration of immune cells and a subsequent activation of hepatic stellate cells. Chemokines are ubiquitous chemotactic proteins which are involved in inflammatory pathways. It has been recently suggested that chemokines can also induce the expression of other chemokines and thereby indirectly regulate immune cell recruitment. We therefore investigated the ability of the chemokine CXCL9 to induce CXCL1, an important neutrophil chemoattractant. Methods: The ability of CXCR3 ligands CXCL9 and CXCL10 to induce CXCL1 expresssion was analyzed in immortalized (GRX) and primary hepatic stellate cells isolated from wild-type and CXCR3-/mice. Cells were treated with different concentrations of chemokines in the absence and presence of pertussis toxin. Furthermore, mice were treated systemically with CXCL9 and hepatic CXCL1 levels as well as neutrophil infiltration were assessed. Results: Treatment of GRX cells with CXCL9 leads to a dose dependent induction of CXCL1 protein expression. This stimulatory effect was validated in primary hepatic stellate cells (P<0.01). In contrast, stimulation of stellate cells with CCL2 did not result in CXCL1 induction. Increased CXCL1 expression in response to CXCL9 was completely abolished by co-incubation with pertussis toxin and in stellate cells derived from CXCR3-/mice, the canonical receptor for CXCL9 and CXCL10. Notably, systemic treatment of mice with CXCL9 led to elevated hepatic CXCL1 levels and was associated with enhanced neutrophil infiltration into the liver. Conclusions: The study describes a chemokine-chemokine pathway in hepatic stellate cells which leads to augmented infiltration of neutrophils into the liver during acute liver injury.

Research paper thumbnail of Proteomic Profiling of Secreted Proteins for the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells

Cell Transplantation, 2013

Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly imp... more Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the most comprehensive proteomic profiling of the HUVEC secretome and identified 827 different secreted proteins. Two hundred and thirty-one proteins were found in all conditions, whereas 369 proteins were identified only under proinflammatory conditions following IL-1β, IL-3, and IL-6 stimulation. Thirteen proteins including complement factor b (CFb) were identified only under IL-1β and IL-3 conditions and may potentially represent HSPC proliferation factors. The combination of bioinformatics and gene ontology annotations indicates the role of the complement system and its activation. Furthermore, CFb was found to be transcriptionally strongly upregulated. Addition of complement component 5b-9 (C5b-9) monoclonal antibody to the stem cell ...

Research paper thumbnail of Homozygous sequence variants in the FKBP10 gene underlie osteogenesis imperfecta in consanguineous families

Journal of Human Genetics, 2015

Osteogenesis imperfecta (OI, MIM 610968) is a genetically and clinically heterogeneous disorder c... more Osteogenesis imperfecta (OI, MIM 610968) is a genetically and clinically heterogeneous disorder characterized by bone fragility. It is one of the rare forms of skeletal deformity caused by sequence variants in at least 14 different genes, including FKBP10 (MIM 607063) encoding protein FKBP65. Here we present three consanguineous families of Pakistani origin segregating OI in an autosomal-recessive pattern. Genotyping using either single-nucleotide polymorphism markers by Affymetrix GeneChip Human Mapping 250K Nsp array or polymorphic microsatellite markers revealed a homozygous region, containing a candidate gene FKBP10, among affected members on chromosome 17q21.2. Sequencing the FKBP10 gene revealed a homozygous novel nonsense variant (c.1490G4A, p.Trp497*) in the family A and two previously reported variants, including a missense (c.344G4A, p.Arg115Gln), in the family B and duplication of a nucleotide C (c.831dupC, p.Gly278ArgfsX295) in the family C. Our findings further extend the body of evidence that supports the importance of FKBP10 gene in the development of skeletal system.

Research paper thumbnail of Chemokine Cxcl9 attenuates liver fibrosis-associated angiogenesis in mice

Hepatology (Baltimore, Md.), 2012

Recent data suggest that the chemokine receptor CXCR3 is functionally involved in fibroproliferat... more Recent data suggest that the chemokine receptor CXCR3 is functionally involved in fibroproliferative disorders, including liver fibrosis. Neoangiogenesis is an important pathophysiological feature of liver scarring, but a functional role of angiostatic CXCR3 chemokines in this process is unclear. We therefore investigated neoangiogenesis in carbon tetrachloride (CCl(4))-induced liver fibrosis in Cxcr3(-/-) and wildtype mice by histological, molecular, and functional imaging methods. Furthermore, we assessed the direct role of vascular endothelial growth factor (VEGF) overexpression on liver angiogenesis and the fibroproliferative response using a Tet-inducible bitransgenic mouse model. The feasibility of attenuation of angiogenesis and associated liver fibrosis by therapeutic treatment with the angiostatic chemokine Cxcl9 was systematically analyzed in vitro and in vivo. The results demonstrate that fibrosis progression in Cxcr3(-/-) mice was strongly linked to enhanced neoangiogene...