Green synthesis of Superparamagnetic Iron Oxide and Silver Nanoparticles in Satureja hortensis Leave Extract: Evaluation of Antifungal Effects on Botryosphaeriaceae Species.

In recent years, green synthesis methods of metallic nanoparticles (MNPs) have been attractive because of the more facile, cheaper, and appropriate features associated with biomolecules in MNPs biosynthesis. This research represented an easy, fast, and environmentally friendly method to biosynthesis of superparamagnetic iron oxide nanoparticles (SPIONPs) and silver nanoparticles (AgNPs) by the Satureja hortensis leaf extract as stabilizer and reducer. The SPIONPs synthesized in co-precipitation method. The biosynthesized SPIONPs and AgNPs were studied their antifungal effects against three Botryosphaeriaceae plant pathogens, Botryosphaeria dothidea, Diplodia seriata, and Neofusicoccum parvum. UV-visible spectra (UV-Vis), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), field emission scanning electron microscopy (Fe-SEM), energy-dispersive X-ray spectroscopy (EDX), and vibrating-sample magnetometer (VSM) analyses were used to evaluate the physicochemical properties and verify the formation of green synthesized SPIONPs and AgNPs. UV-Vis spectra revealed absorption peaks at 243 and 448 nm for SPIONs and 436 nm for AgNPs, respectively. Microscopic and XRD analysis showed that SPIONPs and AgNPs was found spherical in shape with an average particle size of SPIONPs and AgNPs 10 and 12 nm, respectively. The antifungal test against Botryosphaeriaceae species showed that SPIONPs and AgNPs possess antifungal properties against B. dothidea, D. seriata, and N. parvum. However, AgNPs exhibits greater antifungal activity than SPIONPs. The results of the cytotoxicity tests of SPIONs and AgNPs on the MCF-7 cell line showed that AgNPs was significantly more cytotoxic towards the MCF-7 cell line, whereas no significant cytotoxic effect was recorded by SPIONs. Therefore, these biosynthesized MNPs could be substituted for toxic fungicides that are extensively applied in agriculture and contribute to environmental health and food safety.

Unraveling the influence of TiO2 nanoparticles on growth, physiological and phytochemical characteristics of Mentha piperita L. in cadmium-contaminated soil.

Among the metals contaminants, cadmium (Cd) is one of the most toxic elements in cultivated soils, causing loss of yield and productivity in plants. Recently, nanomaterials have been shown to mitigate the negative consequences of environmental stresses in different plants. However, little is known about foliar application of titanium dioxide nanoparticles (TiO2 NPs) to alleviate Cd stress in medicinal plants, and their dual interactions on essential oil production. The objective of this study was to investigate the effects of foliar-applied TiO2 NPs on growth, Cd uptake, chlorophyll fluorescence, photosynthetic pigments, malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, total phenols, anthocyanins, flavonoids, antioxidant enzymes (SOD, CAT and POD) activity and essential oil content of Mentha piperita L. (peppermint) under Cd stress. For this purpose, plants were grown in Cd-contaminated (0, 20, 40, and 60 mg L-1) soil, and different concentrations of TiO2 NPs (0, 75, and 150 mg L-1) were foliar sprayed at three times after full establishment until the beginning of flowering. Exposure to TiO2 NPs significantly (P < 0.01) increased shoot dry weight (37.8%) and the number of lateral branches (59.4%) and decreased Cd uptake in plant tissues as compared to the control. Application of TiO2 NPs increased the content of plastid pigments, and the ratio Fv/Fm (13.4%) as compared to the control. Additionally, TiO2 NPs reduced the stress markers, MDA and H2O2 contents and enhanced the activity of the phenylalanine ammonia-lyase (PAL) enzyme (60.5%), total phenols (56.1%), anthocyanins (42.6%), flavonoids (25.5%), and essential oil content (52.3%) in Cd-stressed peppermint compared to the control. The results also demonstrated that foliar spray of TiO2 NPs effectively improved the growth and chlorophyll fluorescence parameters and reduced Cd accumulation in peppermint, which was mainly attributed to the reduction of oxidative burst and enhancement of the enzymatic (SOD, CAT, and POD) antioxidant defense system due to the uptake of NPs. The findings provide insights into the regulatory mechanism of TiO2 NPs on peppermint plants growth, physiology and secondary metabolites production in Cd-contaminated soil.

Antileishmanial, cellular mechanisms, and cytotoxic effects of green synthesized zinc nanoparticles alone and in combined with glucantime against Leishmania major infection.

BACKGROUND: We decided to investigate the antileishmanial, cellular mechanisms, and cytotoxic effects of green synthesized Zinc nanoparticles (ZnNPs) alone and combined with glucantime against Leishmania major infection. METHODS: The effect of green synthesized ZnNP on L. major amastigote was studied through macrophage cells. The mRNA expression level of iNOS and IFN-γ followed by the exposure of J774-A1 macrophage cells to ZnNPs was assessed by Real-time PCR. The Caspase-3-like activity of promastigotes exposed to ZnNPs was studied. Effects of ZnNPs alone and combined with glucantime (MA) were studied on cutaneous leishmaniasis in BALB/c mice. RESULTS: ZnNPs displayed the spherical shape with sizes ranging from 30 to 80 nm. The obtained IC50 values for ZnNPs, MA, and ZnNPs + MA were 43.2, 26.3, and 12.6 µg/mL, respectively; indicating the synergistic effects of ZnNPs in combination with MA. CL lesions had completely improved in the mice received with ZnNPs in combination with MA. The mRNA expression level of iNOS, TNF-α, and IFN-γ was dose-dependently (p < 0.01) upregulated; whereas it was downregulated in IL-10. ZnNPs markedly stimulated the caspase-3 activation with no significant toxicity on normal cells. CONCLUSION: Based on these in vitro and in vivo results, green synthesized ZnNPs, mainly along with MA, showed that has the potential to be introduced as a new drug for CL therapy. Triggering of NO production, and inhibition of infectivity rate are revealed as mechanisms of action ZnNPs on L. major. But, supplementary investigations are necessary to clear the efficacy and safety of these agents.

Repurposing of sevelamer as a novel antidote against aluminum phosphide poisoning: An in vivo evaluation.

Aluminum phosphide (AlP) is widely used for protecting grains from pests. AlP releases toxic phosphine gas (PH3) while exposed to humidity. Poisoning with these tablets is dangerous and can cause death or serious injuries. Up to now, no definite antidote has been introduced for specific treatment of this poisoning. Sevelamer carbonate or sevelamer hydrochloride (Renagel) is a polymeric pharmaceutical prescribed for treating hyperphosphatemia in patients with chronic kidney disease. Sevelamer can bind with phosphate groups and act as an anion exchanger. Herein, sevelamer is repurposed as a potent antidote agent in phosphine gas poisoning. In vivo evaluation was conducted on male Sprague Dawley rats. The evaluation was conducted on three groups of animals: control, AlP-poisoned, and AlP-poisoned treated with sevelamer. Survival percentage, serum biomarkers level of organ injury, and ATP level were recorded. The results indicate a high survival rate in sevelamer-treated animals compared with the AlP-poisoned group (75% vs. 0% respectively, 48 h after poisoning). The analysis of serum markers of organ injury also showed that sevelamer could reduce toxicity and organ injury in poisoned animals. ATP level of separate organs showed that sevelamer treated groups were recovered. The results showed that sevelamer could be a potent antidote for managing aluminum phosphide poisoning. Moreover, a mechanism is suggested for the interaction of sevelamer with phosphine gas.

Hemostatic efficacy of composite polysaccharide powder (starch-chitosan) for emergency bleeding control: An animal model study.

BACKGROUND: Blood clot formation or hemostasis is vital to minimize blood loss and mitigate the risk of death from severe bleeding. This study investigates the characteristics of a novel hemostatic composite containing chemically modified chitosan and starch for emergency bleeding control. The performance of this novel hemostatic powder was compared with commercially available starch-based (Arista AH) and chitosan-based (Celox) hemostats. METHODS: Hemostatic composite was prepared according to the patent registered by the authors (Patent No. 100865, Iranian Intellectual Property Organization) in Bani Zist Baspar Healda, Inc. (Shiraz, Iran). The properties of the product were surveyed by Fourier-transform infrared spectroscopy and compared with Arista-AH and Celox as commercial counterparts. The cytocompatibility, hemolysis, platelet and red blood cells (RBCs) adhesion, biocompatibility, and biodegradability attributes were evaluated in in vivo and in vitro studies. Hemostatic efficacy was evaluated in 24 healthy 6-month-old male New Zealand white rabbits in lethal and sublethal injuries of femoral artery and veins, respectively. RESULTS: Modification and composition led to a fundamental development in physicochemical characteristics including swelling properties, water absorption, and platelet and RBC adhesion due to improved electrostatic and hydrophilic attributes. The significant superiority in clotting efficiency was confirmed after the application of the composite in 2 models of venous and arterial injury in comparison with common commercial hemostats. CONCLUSION: Simultaneous use of water-absorbing compounds and introducing positively charged functional groups to hemostatic material led to a considerable control of femoral bleeding in emergency conditions. The introduced composite was biodegradable and biocompatible and prompts RBC aggregation and platelet adhesion.

Mitral and aortic valve regurgitation following surgical and transcatheter perimembranous ventricular septal defect closure in children and adolescents: midterm outcomes.

BACKGROUND: Closure of perimembranous ventricular septal defects (pmVSD), either surgical or percutaneous, might improve or cause new-onset mitral regurgitation (MR) and aortic regurgitation (AR). We aimed to evaluate the changes in MR and AR after pmVSD closure by these two methods. MATERIAL AND METHOD: We performed a comparative retrospective data review of all pediatric patients with pmVSDs treated at our institution with surgical or antegrade percutaneous methods from 2014 to 2019 and 146 consecutive patients under 18 years were enrolled. We closely looked at the mitral and aortic valve function after repair. Included patients had no or lower than moderate aortic valve prolapse and baseline normal mitral or aortic valve function or less than moderate MR or AR. RESULTS: Out of 146 patients, 83 (57%) pmVSDs were closed percutaneously, and 63 (43%) pmVSDs were closed surgically. 80 and 62 patients were included for MR evaluation, and 81 and 62 patients for AR evaluation in percutaneous and surgical groups. The mean follow-up time was 40.48 ± 21.59 months in the surgery group and 20.44 ± 18.66 months in the transcatheter group. Mild to moderate degrees of MR and AR did not change or decreased in most patients. In detail, MR of 70% and AR of 50% of the valves were resolved or decreased in both groups. 13% of patients with no MR developed trivial to mild MR, and 10% of patients with no AR showed mild to moderate AR after pmVSD closure in both methods. There was no significant difference between the two methods regarding emerging new regurgitation or change in the severity of the previous regurgitation. CONCLUSION: pmVSD closure usually improves mild to moderate MR and AR to a nearly similar extent in both percutaneous and surgical methods among children and adolescents. It might lead to the onset of new MR or AR in cases with no regurgitation.

Oncogenic and tumor suppressor genes expression in myeloproliferative neoplasms: The hidden side of a complex pathology.

BACKGROUND: The present study aimed to explore the changes in the expressions of six tumor-related genes in myeloproliferative neoplasms (MPNs). The study population included 130 patients with MPNs (52 with chronic myeloid leukemia (CML), 49 with essential thrombocythemia (ET), 20 with polycythemia vera (PV), and 9 with primary myelofibrosis (PMF)) and 51 healthy individuals. METHODS: The expression profiling of six genes (ADAMTS18, CMTM5, CDKN2B, DCC, FHIT, and WNT5B) in the peripheral blood granulocyte cells was explored by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: The patients with MPNs showed significant downregulation of CMTM5 (EFC = 0.66) and DCC (EFC = 0.65) genes in contrast to a non-significant upregulation of ADAMTS18, CDKN2B, FHIT, and WNT5B genes. Downregulation of DCC was consistent in all subtypes of MPN (EFC range: 0.591-0.860). However, CMTM5 had a 1.22-fold upregulation in PMF in contrast to downregulation in other MPN subtypes (EFC range: 0.599-0.775). The results revealed a significant downregulation in CMTM5 and DCC at below 60-years of age. Furthermore, female patients showed a clear-cut downregulation in both CMTM5 and DCC (EFC DCC: 0.436 and CMTM5: 0.570), while male patients presented a less prominent downregulation with a borderline p-value only in DCC (EFC: 0.69; p = 0.05). CONCLUSIONS: Chronic myeloid leukemia cases showed a significant upregulation of WNT5B, as a known oncogenesis gene. Two tumor suppressor genes, namely DCC and CMTM5, were downregulated in the patients with MPNs, especially in females and patients below 60 years of age.

Critical requirement for BCR, BAFF, and BAFFR in memory B cell survival.

Memory B cells (MBCs) are long-lived cells that form a critical part of immunological memory, providing rapid antibody responses to recurring infections. However, very little is known about signals controlling MBC survival. Previous work has shown that antigen is not required for MBC survival, but a requirement for the B cell antigen receptor (BCR) has not been tested. Other studies have shown that, unlike naive B cells, MBCs do not express BAFFR and their survival is independent of BAFF, the ligand for BAFFR. Here, using inducible genetic ablation, we show that survival of MBCs is critically dependent on the BCR and on signaling through the associated CD79A protein. Unexpectedly, we found that MBCs express BAFFR and that their survival requires BAFF and BAFFR; hence, loss of BAFF or BAFFR impairs recall responses. Finally, we show that MBC survival requires IKK2, a kinase that transduces BAFFR signals. Thus, MBC survival is critically dependent on signaling from BCR and BAFFR.

Surgical repair of tetralogy of Fallot using autologous right atrial appendages: short- to mid-term results.

OBJECTIVES: The prevention of pulmonary insufficiency (PI) is a crucial part of the tetralogy of Fallot repair. Many techniques have been introduced to construct valves from different materials for the right ventricular outflow tract, including the most commonly constructed monocusp valves. We are introducing a new bicuspid valve made intraoperatively using the autologous right atrial appendage (RAA) to prevent PI in these patients. METHODS: The RAA valve was constructed and used in 21 patients with tetralogy of Fallot. The effective preservation of the native valve was impossible in all patients because of either a severe valve deformity or a small annulus. The RAA valve was created after ventricular septal defect closure and right ventricular outflow tract myectomy and was covered with a bovine transannular pericardial patch. The perioperative data were evaluated, and the echocardiography results were assessed immediately after operations and in follow-up with a median of 10.5 months. The data were retrospectively compared with 10 other patients with similar demographic data but with only transannular patches. RESULTS: The mean age of the patients was 13.3 months. No mortality or related morbidity occurred after repair using the RAA valve. The PI severity early after the operation was trivial or no PI in 18 patients, and mild PI was observed in 3 patients, which progressed to moderate PI in one of them in the mean 12-month follow-up period. Fifteen patients had mild or no pulmonary stenosis, while moderate pulmonary stenosis was observed in 6 others. Compared with the other 10 patients with only transannular patches, the RAA valve patients had prolonged operative and clamping times, but no difference in postoperative course and shorter hospital stays. The degree of PI was, of course, significantly less in the RAA valve patients, but pulmonary stenosis was the same. CONCLUSIONS: The RAA valve construction is a safe and effective technique to prevent PI after the tetralogy of Fallot repair, at least in terms of short- and mid-term results. A longer follow-up period is needed to confirm if this new valve can eliminate or significantly delay the need for pulmonary valve replacement in these patients.

Management of Persistent Pulmonary Hypertension After Correction of Congenital Heart Defect with Autologous Marrow-Derived Mononuclear Stem Cell Injection into the Pulmonary Artery: A Pilot Study.

Pulmonary arterial hypertension (PAH) related to left-to-right shunt can progress to Eisenmenger syndrome, a serious and fatal disease that is not yet curable. This pilot study considered stem cell injection as a new treatment modality in persistent pulmonary hypertension after the correction of a congenital heart defect. Three patients with persistent pulmonary hypertension after ventricular septal defect repair were included in this pilot study for a clinical trial. Mononuclear stem cells derived from patients' bone marrow specimens were injected into the right and left pulmonary arteries via cardiac catheterization. The patients were followed over a 6-month period, with six-minute walk test, echocardiography and repeated angiography performed in the sixth month after treatment. The results of the study showed improvement of 40 m, 280 m and 100 m in 6-minute walk distance in patients 1 to 3, respectively. The peak PR gradient decreased 2, 5 and 9 mmHg by echocardiography, and mean PA pressure decreased 21, 22 and 9 mmHg by catheterization in patients 1 to 3, respectively. Pulmonary artery resistance decreased 4, 4.5 and 1.3 Wood units after 6 months of stem cell therapy in the three patients. No short-term complications were detected in this pilot trial, and all patients tolerated the procedure without any complications. Intrapulmonary artery injection of stem cells may have a role in the treatment of persistent PAH secondary to congenital heart disease. This procedure is feasible, with no significant complications, and this study can be considered as a platform for larger studies.

The Nephroprotective Role of Carnosine Against Ifosfamide-Induced Renal Injury and Electrolytes Imbalance is Mediated Via the Regulation of Mitochondrial Function and Alleviation of Oxidative Stress.

BACKGROUND: Ifosfamide (IFO) is an alkylating agent administered against different types of malignancies. Several cases of renal injury and serum electrolytes disturbances have been reported in IFO-treated patients. Oxidative stress and mitochondrial dysfunction are suspected of being involved in the mechanism of IFO nephrotoxicity. Carnosine is a dipeptide which its antioxidant and mitochondria protecting properties have been mentioned in different experimental models. The current study aimed to evaluate the nephroprotective properties of carnosine against IFO-induced renal injury. METHODS: Rats were treated with IFO (50 mg/kg, i.p) alone or in combination with carnosine. Serum and urine biomarkers of renal injury in addition to kidney markers of oxidative stress were evaluated. Moreover, kidney mitochondria were isolated, and some mitochondrial indices were assessed. RESULTS: Elevated serum creatinine and BUN, hypokalemia, and hypophosphatemia, in addition, to an increase in urine glucose, protein, γ-GT, and alkaline phosphatase (ALP), were evident in IFO-treated animals. IFO also caused an increase in kidney reactive oxygen species (ROS) and lipid peroxidation (LPO). Renal GSH levels and antioxidant capacity were also depleted with IFO therapy. Mitochondrial dehydrogenase activity, GSH level, membrane potential, and ATP content were decreased while mitochondrial LPO and permeabilization were increased in IFO group. Carnosine (250 and 500 mg/kg, i.p) mitigated IFO-induced oxidative stress and mitochondrial impairment in renal tissue. CONCLUSION: Our data suggest mitochondrial dysfunction and oxidative stress as fundamental mechanisms of renal injury induced by IFO. On the other hand, carnosine supplementation protected kidneys against IFO-induced injury through regulating mitochondrial function and mitigating oxidative stress.

Hemolysis and its outcome following percutaneous closure of cardiac defects among children and adolescents: a prospective study.

BACKGROUND: Transcatheter closure of intracardiac defects might be complicated by intravascular hemolysis. We evaluated hemolysis and its outcome after transcatheter closure of these defects. METHODS AND PATIENTS: All patients who underwent transcatheter closure of patent ductus arteriosus, ventricular septal defect and atrial septal defect were included in this prospective study. Clinical data were obtained before and after the catheterization. RESULTS: One hundred and thirty-eight patients were enrolled; and four (3%) patients developed intravascular hemolysis; while two cases had residual shunt and two other cases had not residual flow. Although residual shunt occurred in ten patients, only 2 of these cases developed hemolysis. Patent ductus arteriosus closure was done for one of these cases and the other one, underwent perimembranous ventricular septal defect closure. Moreover, hemolysis occurred after device closure of patent ductus arteriosus in 2 of the other patients with no residual shunt. In this study the hemolysis was eliminated by conservative management within 2 weeks although residual shunt continued in this time. We observed a decline in lactate dehydrogenase value after catheterization in comparison with precatheterization, which was mainly among ventricular septal defect patients that might be due to mild chronic hemolysis in these patients. CONCLUSION: Incidence of hemolysis after device closure was low, and occurred with and without residual flow and was eliminated by conservative management in 2 weeks, without the need for surgery, although the residual shunt was continued.

Cholestasis-associated reproductive toxicity in male and female rats: The fundamental role of mitochondrial impairment and oxidative stress.

Cholestasis is a significant decrease in bile flow. The liver is the primary organ affected by cholestasis. Chronic cholestasis could entail to tissue fibrotic changes and liver cirrhosis. Other organs, including heart, kidneys, nervous system, skeletal muscles, as well as the reproductive system, might also be affected during cholestasis. Although the cholestasis-associated pathological and biochemical alterations in organs such as liver have been widely investigated, there is little information about complications such as cholestasis-induced reproductive toxicity. The current study aimed to evaluate the pathologic effects of cholestasis on reproductive organs in both male and female animals. Rats underwent bile duct ligation (BDL) surgery. Markers of reproductive toxicity, including serum hormonal changes, tissue histopathological alterations, biomarkers of oxidative stress, and markers of mitochondrial impairment, were evaluated. Increased serum markers of liver injury and elevated level of cytotoxic molecules such as bile acids and bilirubin were evident in BDL animals. On the other hand, the serum level of hormones such as testosterone was suppressed in BDL rats. Significant histopathological alterations were also evident in the testis and ovary of BDL animals. A significant increase in oxidative stress markers, including ROS formation, lipid peroxidation, protein carbonylation, and depleted glutathione and antioxidant reservoirs were also detected in BDL rats. Moreover, mitochondrial depolarization decreased dehydrogenases activity, and depleted ATP content was detected in sperm isolated from the BDL group. These data indicate that cholestasis-associated reproductive toxicity in male and female rats is restrictedly coupled with severe oxidative stress and mitochondrial impairment.

The potential role of mitochondrial impairment in the pathogenesis of imatinib-induced renal injury.

Imatinib is a tyrosine kinase inhibitor widely administered against chronic myeloid leukemia. On the other hand, drug-induced kidney proximal tubular injury, electrolytes disturbances, and renal failure is a clinical complication associated with imatinib therapy. There is no precise cellular mechanism(s) for imatinib-induced renal injury. The current investigation aimed to evaluate the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of imatinib nephrotoxicity. Rats received imatinib (50 and 100 mg/kg, oral, 14 consecutive days). Serum and urine biomarkers of renal injury and markers of oxidative stress in the kidney tissue were assessed. Moreover, kidney mitochondria were isolated, and mitochondrial indices, including mitochondrial depolarization, dehydrogenases activity, mitochondrial permeabilization, lipid peroxidation (LPO), mitochondrial glutathione levels, and ATP content were determined. A significant increase in serum (Creatinine; Cr and blood urea nitrogen; BUN) and urine (Glucose, protein, gamma-glutamyl transferase; γ-GT, and alkaline phosphatase; ALP) biomarkers of renal injury, as well as serum electrolytes disturbances (hypokalemia and hypophosphatemia), were evident in imatinib-treated animals. On the other hand, imatinib (100 mg/kg) caused an increase in kidney ROS and LPO. Renal tubular interstitial nephritis, tissue necrosis, and atrophy were evident as tissue histopathological changes in imatinib-treated rats. Mitochondrial parameters were also adversely affected by imatinib administration. These data represent mitochondrial impairment, renal tissue energy crisis, and oxidative stress as possible mechanisms involved in the pathogenesis of imatinib-induced renal injury and serum electrolytes disturbances.

Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study.

BACKGROUND: Cyclophosphamide (CP), as an anticancer agent, causes ovarian toxicity and subsequent infertility in women. Atorvastatin (ATV) at a low dose has antioxidant and anti-inflammatory properties. OBJECTIVE: The aim of this study was to investigate the protective effect of ATV against CP-induced ovarian injury in rat. MATERIALS AND METHODS: In this experimental study, thirty-two female Wistar rats were randomly divided into four groups as I) control, II) ATV (10 mg/kg), III) CP (150 mg/kg), and IV) CP +ATV. The ATV treated groups were received ATV for 10 days via oral gavage. In the CP+ATV group, ATV was administrated on 5 days before and 5 days after CP injection. Histological structure, apoptosis (caspase-3), oxidative stress parameters as malondialdehyde, reactive oxygen species, protein carbonyl levels and cell viability were evaluated in ovary tissue by histological scores, immunohistochemistry, histochemical and biochemical assays. The levels of estrogen and progesterone hormones were measured on the 12th day of study. RESULTS: ATV pretreatment significantly decreased the levels of oxidative stress biomarkers as malondialdehyde, reactive oxygen species and protein carbonyl levels and increased cell death in CP-treated rats as compared with the CP alone group. ATV significantly increased estrogen and progesterone levels in CP-treated rats. In addition, the histological examination showed ATV mitigated acute inflammation, degenerative cells in stroma and follicles, stromal edema, vacuolization, atresia of the follicles and congestion of blood vessels in the CP-treated animals. Furthermore, ATV significantly reduced immunoreactivity level of caspase-3 in CP-treated rats. CONCLUSION: Our results showed that the ATV with antioxidant and anti-apoptosis (caspase-3) activities protected ovarian against CP-induced toxicity.

Publisher Correction: Mechanisms and impact of altered tumour mechanics.

In the version of this Review originally published, owing to a technical error the text 'However, given the multitude' was incorrectly introduced after the sentence beginning 'The transition to a mesenchymal state is characterized...'. This has now been amended in all online versions of the Review.

Mechanisms and impact of altered tumour mechanics.

The physical characteristics of tumours are intricately linked to the tumour phenotype and difficulties during treatment. Many factors contribute to the increased stiffness of tumours; from increased matrix deposition, matrix remodelling by forces from cancer cells and stromal fibroblasts, matrix crosslinking, increased cellularity, and the build-up of both solid and interstitial pressure. Increased stiffness then feeds back to increase tumour invasiveness and reduce therapy efficacy. Increased understanding of this interplay is offering new therapeutic avenues.

Zatariamultiflora ameliorates cisplatin-induced testicular damage via suppression of oxidative stress and apoptosis in a mice model.

OBJECTIVES: Cisplatin (CP), as an anti-neoplastic drug, causes testicular damage. Zataria multiflora Boiss (ZM), a medicinal plant, has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of ZM against CP-induced testicular toxicity. MATERIALS AND METHODS: In this experimental study, thirty-two adult male mice were randomly divided into four groups. The control group received normal saline with oral gavage during 7 days; ZM group received ZM (200 mg/kg) during 7 days by gavage; CP group received CP (10 mg/kg) intraperitoneally (IP) in the 5th day of study; ZM + CP group received ZM during 7 days and CP was injected in 5th day. Sperm parameters, biochemical (MDA, GSH, and PC) levels, serum testosterone levels, and histopathological and immunohistochemical assays of testis were examined one day after the last drug treatment. RESULTS: CP treatment caused significant damage via changed sperm parameters (sperm motility, count, viability rate, and abnormalities), increased oxidative stress (increased MDA and PC levels, and decreased GSH level), histological changes (degeneration, necrosis, arrest of spermatogenesis, congestion, and decrease in thickness of the germinal epithelium, diameter of seminiferous tubules, and Johnsen's Score), decreased serum testosterone level, and increased caspase-3 immunoreactivity. ZM preserved spermatogenesis and mitigated the toxic effects of CP on the testis tissue. In addition, treatment with ZM significantly reduced caspase-3 immunoreactivity. CONCLUSION: The findings of this study suggest that ZM as a potential antioxidant compound and due to free radicals scavenging activities has a protective effect against CP-induced testicular toxicity.

Biochemical and Cellular Determinants of Renal Glomerular Elasticity.

The elastic properties of renal glomeruli and their capillaries permit them to maintain structural integrity in the presence of variable hemodynamic forces. Measured by micro-indentation, glomeruli have an elastic modulus (E, Young's modulus) of 2.1 kPa, and estimates from glomerular perfusion studies suggest that the E of glomeruli is between 2 and 4 kPa. F-actin depolymerization by latrunculin, inhibition of acto-myosin contractility by blebbistatin, reduction in ATP synthesis, and reduction of the affinity of adhesion proteins by EDTA reduced the glomerular E to 1.26, 1.7, 1.5, and 1.43 kPa, respectively. Actin filament stabilization with jasplakinolide and increasing integrin affinity with Mg2+ increased E to 2.65 and 2.87 kPa, respectively. Alterations in glomerular E are reflected in commensurate changes in F/G actin ratios. Disruption of vimentin intermediate filaments by withaferin A reduced E to 0.92 kPa. The E of decellularized glomeruli was 0.74 kPa, indicating that cellular components of glomeruli have dominant effects on their elasticity. The E of glomerular basement membranes measured by magnetic bead displacement was 2.4 kPa. Podocytes and mesangial cells grown on substrates with E values between 3 and 5 kPa had actin fibers and focal adhesions resembling those of podocytes in vivo. Renal ischemia and ischemia-reperfusion reduced the E of glomeruli to 1.58 kPa. These results show that the E of glomeruli is between 2 and 4 kPa. E of the GBM, 2.4 kPa, is consistent with this value, and is supported by the behavior of podocytes and mesangial cells grown on variable stiffness matrices. The podocyte cytoskeleton contributes the major component to the overall E of glomeruli, and a normal E requires ATP synthesis. The reduction in glomerular E following ischemia and in other diseases indicates that reduced glomerular E is a common feature of many forms of glomerular injury and indicative of an abnormal podocyte cytoskeleton.

Association of HaeIII single nucleotide polymorphisms in the SLC2A1 gene with risk of diabetic nephropathy; evidence from Kurdish patients with type 2 diabetes mellitus.

AIMS: Given the growing rate of patients with type 2 diabetes mellitus, uncovering the effects of gene polymorphism on diabetes pathogenesis has attracted a lot of attention. Because glucose transporter 1 is involved in glucose uptake, the polymorphism of this gene may be an important risk factor in type 2 diabetes mellitus or in the progression of diabetes complications such as diabetic nephropathy. As far as the authors are concerned, this study is the first one aiming at evaluating the probable effects of solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism on clinical and laboratory outcomes of Kurdish patients with type 2 diabetes mellitus. METHODS: This study was conducted involving 126 diabetic nephropathy patients and 150 diabetic patients without renal involvement. Serum levels of Cystatin C, fasting blood glucose, creatinine and urinary albumin; levels of glycated hemoglobin and estimated glomerular filtration rate were measured. Moreover, the Hae III polymorphism of SLC2A1 gene was determined by PCR-restriction fragment length polymorphism (RFLP). RESULTS: The rate of CC genotype was higher (37%) in patients with diabetic nephropathy compared with controls. There were a significant correlation between the CC genotype and risk of diabetic nephropathy. There were significant correlations between genotypes, serum Cystatin C and estimated glomerular filtration rate in patients with diabetic nephropathy. CONCLUSIONS: The results demonstrated the high frequency of C allele of SLC2A1 HaeIII in Kurdish patients with diabetic nephropathy. It was also found that this polymorphism is a significant risk factor for diabetic nephropathy. The effect of this polymorphism on clinical and laboratory characteristics of diabetic nephropathy patients was significant.