Leaves of Cordia boissieri A. DC. as a potential source of bioactive secondary metabolites for protection against metabolic syndrome-induced in rats.

Cordia boissieri A. DC. (Boraginaceae) is traditionally used as an herbal remedy for diabetes by Hispanic women in Southwestern USA. A recent investigation showed the significant protective effect of ethyl acetate extract against metabolic syndrome (MS). However, the corresponding active principles responsible for this effect and relations between their structure and biological actions remain unclear. Thus, ethyl acetate extract was subjected to column chromatography, which yielded seven compounds identified on the basis of spectroscopic data as rutin, hesperidin, kaempferol-3-O-ß-d-glucopyranoside, rosmarinic acid, ß-sitosterol-3-O-ß-d-glucopyranoside, quercetin, and kaempferol. The isolated compounds (5 mg/kg/day) were tested in a fructose enriched-diet rat model using metformin as a standard drug. Blood samples were withdrawn for estimation of MS-associated biomarkers and liver samples were subjected to histopathological and immunohistochemical examination. The isolated compounds impaired most of the changes associated with MS as evidenced by improved insulin sensitivity, glucose tolerance, kidney function, lipid profiles and reduced oxidative stress and inflammation by different degrees. It is worth noting that quercetin and kaempferol showed the most potent effect. Structure-activity relationship study revealed that the presence of 2,3-double bond in ring C and ortho-hydroxylation in ring B increases the flavonoids activity while glycosylation or methylation decreased this activity.

Anticancer effect of propranolol on diethylnitrosamine-induced hepatocellular carcinoma rat model.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non-selective ß-blocker propranolol demonstrated antiproliferative activity in many cancer types. OBJECTIVE: This investigation aimed to evaluate the anticancer effect of propranolol against DEN-induced HCC in rats. METHODS: Thirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b.wt.) once a week for 10 weeks, to induce HCC, and Group III (HCC/Prop); received DEN for 10 weeks for HCC induction, then received 20 mg/kg b.wt. propranolol, intraperitoneally for four successive weeks. RESULTS: HCC was developed in rats' livers and confirmed via significant liver architecture changes, significantly elevated activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-fetoprotein (AFP), total- and direct-bilirubin (Bil), and a decline in albumin (ALB) level in serum. HCC group demonstrated elevated levels of malondialdehyde (MDA), nitric oxide (NO), HIF-1α, IL-8, NF-κB, PGE2, TGF-ß1, VEGF, and CD8, but significant decline of GSH, and IL-10 level, with suppression of the antioxidant enzymes' activities. In addition, the gene expression of the hepatic inducible nitric oxide synthase (iNOS), and LAG-3 were up-regulated. Moreover, the protein expression of p-PKC was up-regulated, while that of PD-1 and PD-L1 were down-regulated in the liver tissues of the HCC group. However, propranolol ameliorated the investigated parameters in the HCC/Prop group. CONCLUSION: Propranolol exhibited an anticancer effect and thus can be considered as a promising treatment for HCC. Blocking of PD-1/PD-L1 and LAG-3 signals participated in the anti-tumor effect of propranolol on HCC.

Ubiquinol attenuates γ-radiation induced coronary and aortic changes via PDGF/p38 MAPK/ICAM-1 related pathway.

Endothelial vascular injury is one of the most pivotal disorders emerging during radiotherapy. It is crucial to rely on strong antioxidants to defend against vascular damage. The current study was carried out to investigate the ameliorative effect of ubiquinol (Ubq) against gamma (γ)-radiation induced aortic and coronary changes, with highlighting its role in suppression of p38 mitogen activated protein kinase (MAPK). Exposure to γ-radiation was adopted as a potent detrimental model that induces vascular tissue damage. Concisely, male albino rats were irradiated at a dose level of 7 Gy and treated daily with Ubq (10 mg/kg/day, p.o.) for 7 days pre-and post-irradiation. At the end of the experiment, lipid profile, 8-hydroxydeoxyguanosine (8-OHdG), gene expression of intercellular adhesion molecule (ICAM-1), platelet derived growth factor (PDGF), p38 MAPK and matrix metalloproteinase-9 (MMP-9) were estimated. Exposure to radiation significantly deteriorates aortic and coronary tissues. Conversely, administration of Ubq significantly reduced serum t-cholesterol, LDL and triglycerides (p = 0.001). In addition, Ubq prevented oxidative DNA damage (8-OHdG) (p = 0.1) and reduced serum MMP-9 (p = 0.001) which contributed to the endothelial cells damage. The positive impact of Ubq was more apparent in suppression of both PDGF (p = 0.001) and p38 MAPK (p = 0.1) protein concentrations, leading subsequently in reduction of ICAM-1 (p = 0.001) gene expression. As a conclusion, vascular endothelial damage brought on by γ-radiation is one of the leading causes of coronary and aortic deteriorations which could be successfully mitigated by Ubq.

Immediate implant placement with platelet rich fibrin as space filling material versus deproteinized bovine bone in maxillary premolars: A randomized clinical trial.

BACKGROUND: Several biomaterials have been suggested to augment the jumping gap during immediate implant placement. PURPOSE: The aim of this study was to compare the effect of xenograft or platelet derived growth factor (PRF) to graft the jumping gap in immediate implant placement in the maxillary premolar region. MATERIALS AND METHODS: Twenty patients underwent atraumatic extraction followed by immediate placement. The patients were equally divided into two groups. The first group received xenograft as a jumping gap filling material. The second group received PRF to graft the jumping gap. All patients received preoperative, immediate postoperative, and 6 months postoperative cone beam CT scan (CBCT). Implant stability quotient ISQ values were taken for the installed implants immediate postoperative and at 6 months. RESULTS: Implants receiving PRF as a jumping gap graft material demonstrated a significantly greater amount of crestal bone loss 1.85 ± 0.89 mm as compared to xenograft group 0.77 ± 0.32 mm (t = 3.52, p = 0.005). PRF group showed significantly greater reduction in buccopalatal direction 1.63 mm as compared to xenograft group 0.59 mm (t = 4014, p <0.001). ISQ values were similar immediately postoperative (t = 0.070, p = 0.945) while the ISQ values were significantly lower in PRF group as compared to xenograft graft at the six-month interval (t = 0.248, p = 0.023). CONCLUSION: The use of xenograft material as a jumping gap filling material resulted in superior results compared to PRF with regards to crestal bone loss, buccolingual socket reduction, and ISQ values.

Nanoparticles Loaded Thermoresponsive In Situ Gel for Ocular Antibiotic Delivery against Bacterial Keratitis.

Antibiotics delivered through conventional dosage against ophthalmic infections show lower therapeutic efficacy due to their low residence time. Therefore, there is a great need to design and develop novel dosage forms that would increase the ocular residence time of antibiotics at the site of infection. This study describes the development of nanoparticles laden in situ gelling solution, intended to sustain antibiotic release for improved therapeutic efficiency. Oxytetracycline-loaded gelatin-polyacrylic acid nanoparticles were prepared and incorporated in poloxamer-N407 solution. The rheological properties of the system were studied concerning time and temperature. Moreover, in vivo biocompatibility of the system was ascertained using the Draize test and histological studies. Finally, the optimized formulation was evaluated for in vitro antibacterial activity against one of the most common keratitis causing bacteria, Pseudomonas aeruginosa. Additionally, the in vivo efficacy was evaluated on the rabbit's eye conjunctivitis model. The formulation showed a sustained effect against keratitis; furthermore, the antibacterial activity was comparable with the commercial product.

miR-150-PTPMT1-cardiolipin signaling in pulmonary arterial hypertension.

Circulating levels of endothelial miR-150 are reduced in pulmonary arterial hypertension (PAH) and act as an independent predictor of patient survival, but links between endothelial miR-150 and vascular dysfunction are not well understood. We studied the effects of endothelial miR-150 supplementation and inhibition in PAH mice and cells from patients with idiopathic PAH. The role of selected mediators of miR-150 identified by RNA sequencing was evaluated in vitro and in vivo. Endothelium-targeted miR-150 delivery prevented the disease in Sugen/hypoxia mice, while endothelial knockdown of miR-150 had adverse effects. miR-150 target genes revealed significant associations with PAH pathways, including proliferation, inflammation, and phospholipid signaling, with PTEN-like mitochondrial phosphatase (PTPMT1) most markedly altered. PTPMT1 reduced inflammation and apoptosis and improved mitochondrial function in human pulmonary endothelial cells and blood-derived endothelial colony-forming cells from idiopathic PAH. Beneficial effects of miR-150 in vitro and in vivo were linked with PTPMT1-dependent biosynthesis of mitochondrial phospholipid cardiolipin and reduced expression of pro-apoptotic, pro-inflammatory, and pro-fibrotic genes, including c-MYB, NOTCH3, transforming growth factor ß (TGF-ß), and Col1a1. In conclusion, we are the first to show that miR-150 supplementation attenuates pulmonary endothelial damage induced by vascular stresses and may be considered as a potential therapeutic strategy in PAH.

Autogenous interpositional block graft vs onlay graft for horizontal ridge augmentation in the mandible.

BACKGROUND: Interpositional block graft revealed promising results in vertical ridge augmentation in the mandible, while scarce evidence is available regarding the use of interpositional block graft for horizontal ridge augmentation in the mandible. PURPOSE: To compare the efficacy of autogenous block interpositional graft vs onlay graft in terms of horizontal ridge augmentation in the mandible. MATERIALS AND METHODS: Twenty patients were randomly divided in two groups interpositional and onlay groups, using autogenous blocks harvested from the mandibular symphysis as the donor site. For the interpositional group, the mandibular ridge was split and the harvested block was inserted in the created space and fixated using titanium screws. For the onlay group, the defect site was decorticated and the harvested block was firmly fixated buccally using titanium screws. Immediate and 4 months postoperative cone beam computed tomography scans were taken for assessment. RESULTS: In the interpositional group, the mean preoperative bone width was 3.85 ± 0.6 mm, after 4 months, the mean bone width was 8.84 ± 0.54 mm. While in the onlay group, the mean preoperative bone width was 3.74 ± 0.83 mm while after 4 months the mean bone width was 7.37 ± 1.98 mm. this was statistically significant. CONCLUSION: Within the limits of this study, interpositional block graft appears to be a viable treatment option for horizontal ridge augmentation in the mandible.

Gold Nanorod-Assisted Photothermal Therapy Decreases Bleeding during Breast Cancer Surgery in Dogs and Cats.

For localized tumors, gold nanorod (AuNR)-assisted plasmonic photothermal therapy (PPTT) is a potentially effective alternative to traditional surgery, in which AuNRs absorb near-infrared light and convert it to heat in order to kill cancer cells. However, for large tumors (volume ≥ 20 cm3), an uneven distribution of AuNRs might cause inhomogeneity of the heat distribution inside the tumor. Surgery is frequently recommended for removing large tumors, but it is associated with a high risk of cancer recurrence and metastasis. Here, we applied PPTT before surgery, which showed improved treatment for large tumors. We divided the animals (eight cats/dogs) into two groups: Group I (control), where three cases were solely treated with surgery, laser, or AuNRs alone, resulting in recurrence and metastasis; and Group II, where animals were treated with PPTT before surgery. In Group II, four out of the five cases had tumor regression without any recurrence or metastasis. Interestingly, we observed that applying PPTT before surgery displayed reduced bleeding during tumor removal, supported by histopathology that showed altered blood vessels. In conclusion, our study showed that applying AuNR-assisted PPTT (AuNRs-PPTT) before surgery could significantly affect blood vessels inside the tumor, leading to a decreased amount of bleeding during surgery, which can potentially decrease the risk of metastasis and blood loss during surgery.

Computer-guided chin harvest: A novel approach for autogenous block harvest from the mandibular symphesis.

BACKGROUND: The introduction of CAD/CAM technology allowed clinicians to carry out complex procedures with a high level of precision and reproducibility and minimize the risk of injury during the procedure. PURPOSE: The aim of the present study is to evaluate the efficacy of the CAD/CAM surgical guide during chin harvesting procedures in reducing the risk of neurosensory damage and patient morbidity compared with the standard technique. MATERIALS AND METHODS: About 20 cases of autogenous block chin harvest were randomly into two groups. The first group received computer-guided chin block harvest while the second group received autogenous block chin harvest using the standard approach. RESULTS: In the guided group, out of the 10 subjects, 2 subjects presented with wound dehiscence which resolved within 1 month. No teeth showed any negative pulp sensitivity results. The pointed-Blunt test and 2 point discrimination tests showed a single case of neurodeficits at 1 week follow-up appointment which resolved within 1 month. In the nonguided group, out of the 10 subjects, 1 case presented with wound dehiscence that resolved completely within 1 month. Pulp vitality test showed negative results in 29.4% of the involved teeth at 1 week which decreased to 9.8% and 3.9% at 1 and 6 months follow-up, respectively. The pointed blunt test revealed 3 subjects with neurodeficits at 1 week, out of which 2 subjects showed persisting symptoms at 6 months follow-up. The 2 point discrimination test showed 3 subjects with neurodeficits, out of which two subjects showed persistent symptoms with no resolution at the 6 months follow-up. CONCLUSION: Within the limits of this study, computer-guided chin harvest shows promising results in the reduction of neurosensory complications following harvesting procedures and presents as a safe alternative to the standard technique.

Computer guided sinus floor elevation through lateral window approach with simultaneous implant placement.

BACKGROUND: The introduction of CAD/CAM technology in implant dentistry has marked a new era, allowing various procedures to be carried out with a level of great precision and accuracy. PURPOSE: The aim of the present study is to compare the efficacy of a CAD/CAM generated surgical cutting guide in the reduction of incidence of membrane perforation during maxillary sinus floor elevation in relation to the standard lateral window approach technique. MATERIALS AND METHODS: Twenty cases of maxillary sinus elevation were randomly divided into 2 groups. The first group received computer guided sinus floor elevation through lateral window approach and simultaneous implant placement while the second group received standard sinus elevation procedure through lateral window approach with simultaneous implant placement. RESULTS: In the computer guided group, 3 out of 10 cases presented with sinus septa, only 1 case suffered from membrane perforation during the elevation process. In the non-guided group, 3 cases suffered from membrane perforation, 2 of which were complicated by sinus septa. CONCLUSION: Within the limits of this study, computer guided sinus floor elevation showed promising results in accurately modifying the lateral window osteotomy and presents as a safe alternative to the standard technique.

Magnesium sulfate versus esomeprazole impact on the neonates of preeclamptic rats.

OBJECTIVE: Preeclampsia represents a major complication of pregnancy, associated with greater maternal and fetal complications. We compared the effects of esomeprazole (a proton pump inhibitor) and magnesium sulfate (MgSO4) on the deleterious effects observed on the mother and neonates in experimentally induced preeclampsia in rats. STUDY DESIGN: Preeclampsia was induced in pregnant rats with NG-nitro-l-arginine methyl ester (L-NAME) starting from day 10-till end of pregnancy. Pregnant rats were divided into four groups: control pregnant; untreated preeclampsia; preeclamptic rats treated with MgSO4 and preeclamptic treated with esomeprazole. Treatment was started on day 14 and continued until end of pregnancy. Systolic blood pressure, gestation duration, the total number of pups/fetal resorption, pups birth weight, and histopathology examination of the pup's organs were recorded. RESULTS: In comparison with the L-NAME group, the MgSO4 and esomeprazole treatment reduced the values of systolic blood pressure; MgSO4 normalized gestational duration while esomeprazole prolonged it (post-term pregnancy); both restored number of delivered pups; with no statistical differences between the numbers of died pups between the four groups studied while with esomeprazole, out of 10 pregnant females, 2 of them had complete intrauterine fetal resorption; esomeprazole normalized birth weight and histological structure of fetal liver, kidney, and brain. On the other side, MgSO4 treatment gave rise to lower than normal birth weight and minimal tissue damage. CONCLUSION: Esomeprazole and MgSO4 improved systolic blood pressure, prevented preterm labor and restored numbers of pups delivered and fetal weight. Esomeprazole prolonged gestational period post-term with subsequent improving reproductive outcome.

Study of the protective effect of ischemic and pharmacological preconditioning on hepatic ischemic reperfusion injury induced in rats.

BACKGROUND AND AIM: Hepatic ischemia reperfusion injury is the main cause of liver failure following liver surgery, so an effective method is needed to prevent or reduce this hepatic injury. The aim of the present study is to investigate the potential effect of ischemic preconditioning versus pharmacological preconditioning with lisinopril or verapamil for protection against hepatic ischemia reperfusion injury induced in rats. METHODS: Rats were divided into six groups. Group I served as control untreated. Rats of group II were subjected to laparotomy without induction of ischemia reperfusion. Ischemia reperfusion by ligation of the portal trait for 30 min, followed by reperfusion for 2 h, was performed in rats of groups III-VI. Ischemic preconditioning was performed for rats of group IV before induction of ischemia reperfusion. Lisinopril and verapamil was given daily for 3 days before induction of ischemia reperfusion in groups V and VI, respectively. Serum level of liver transaminases and liver malondialdehyde content were measured, and hepatic histopathological examination was assessed. RESULTS: Induction of ischemia reperfusion resulted in significant elevation of liver transaminases and liver malondialdehyde content associated with significant hepatic histopathological injury that were significantly improved by ischemic preconditioning, lisinopril, or verapamil treatment. Verapamil showed the most significant improvement compared with ischemic preconditioning or lisinopril treatment. CONCLUSION: Ischemic preconditioning and pharmacological preconditioning by lisinopril or verapamil can protect against hepatic ischemia reperfusion probably through inhibition of oxidative stress and neutrophil infiltration. The most potent protection is demonstrated by verapamil treatment.

Response of Triple Negative Breast Cancer to Neoadjuvant Chemotherapy: Correlation between Ki-67 Expression and Pathological Response.

Triple-negative breast cancers constitute about 15% of all cases, but despite their higher response to neoadjuvant chemotherapy, the tumors are very aggressive and associated with a poor prognosis as well as a higher risk of early recurrence. This study was retrospectively performed on 101 patients with stage II and III invasive breast cancer who received 6-8 cycles of neo-adjuvant chemotherapy. Out of the total, 23 were in the triple negative breast cancer subgroup. Nuclear Ki-67 expression in both the large cohort group (n=101) and triple negative breast cancer subgroup (n=23) and its relation to the pathological response were evaluated. The purpose of the study was to identify the predictive value of nuclear protein Ki-67 expression among patients with invasive breast cancers, involving the triple negative breast cancer subgroup, treated with neoadjuvant chemotherapy in correlation to the rate of pathological complete response. The proliferation marker Ki-67 expression was highest in the triple negative breast cancer subgroup. No appreciable difference in the rate of Ki-67 expression in triple negative breast cancer subgroup using either a cutoff of 14% or 35%. Triple negative breast cancer subgroup showed lower rates of pathological complete response. Achievement of pathological complete response was significantly correlated with smaller tumor size and higher Ki-67 expression. The majority of triple negative breast cancer cases achieved pathological partial response. The study concluded that Ki-67 is a useful tool to predict chemosensitivity in the setting of neoadjuvant chemotherapy for invasive breast cancer but not for the triple negative breast cancer subgroup.

Infectious bacterial pathogens, parasites and pathological correlations of sewage pollution as an important threat to farmed fishes in Egypt.

This paper is a part of a multi-disciplinary research "Application of Decentralized On-Site Water Treatment System in Egypt for Use in Agriculture and Producing Safe Fish and Animal Proteins". The project aimed to investigate the environmental impact of implementing sewage water before and after treatment using the effluent of the on-site decentralized Japanese' Johkasou system, in agriculture and producing fish protein. The aim is to establish such system in Egypt to strengthen the sanitary conditions of water resources. In the present study, the impact of the sewage pollution in some fish farms at El-Fayyum, Port Said and El-Dakahlia governorates in Egypt was carried out. Water and fish (Oreochromis niloticus and Mugil cephalus) samples were collected from private fish farms of such localities. Bacteriological and chemical examination of water samples revealed the existence of coliforms and many other bacterial species of significant human health hazards. The chemical parameters of water showed a marked deviation from normal levels while examination of fish flesh specimens indicated contamination with Streptococcus Sp., Staphylococcus Sp., and Salmonella in all examined localities. Other bacterial isolates of human health importance (Morganella morganii, Pseudomonas cepacia and Enterococcos durans) were identified. The parasitological examination revealed the presence of encysted metacercariae (EMC); Diplostomatidae, Prohemistomatidae and Heterphyidae. Moreover, two protozoan parasites (Mxyoboulus tilapiae and Ichthyophthirius multifilis) were also recorded. The histopathological examination revealed mild tissue reaction in case of bacterial infection and severe pathological lesions in different organs in case of EMC infection. Lamellar hyperplasia and mononuclear cell infiltration in branchial tissue was common findings. In skeletal muscles, atrophy of muscle fibres, myolysis and myophagia were detected.