Potential Impact of SOD2 (rs4880; p.Val16Ala) Variant with the Susceptibility for Childhood Bronchial Asthma.

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

The effects of genetic polymorphism on toxicity and pharmacokinetics of methotrexate in Egyptian adult patients with leukaemia or lymphoma.

Polymorphisms in genes coding folate-metabolising enzymes might alter the pharmacokinetics and sensitivity for methotrexate "MTX".The aim of the study aimed to investigate the influence of MTHFR C677T, DHFR19 Ins/del, GGH -401 C > T, and MTR A2756G polymorphisms on MTX toxicity and pharmacokinetics in Egyptian patients with Acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL).Fifty adult Egyptian patients with ALL and NHL, treated with high dose MTX, were prospectively enrolled in the study. Clinical and biochemical data was collected objectively from medical records after each cycle of MTX. Plasma concentrations of MTX were measured after 72 h of initiation of infusion. Genotyping was done with a PCR-ARMS and PCR-RFLP assays.The MTHFR C677T T variants significantly increased the risk of leukopoenia, whereas the genotype MTHFR 677 C > T TT significantly associated with lymphocytopenia, thrombocytopenia, and anaemia. The genotype GGH-401 TT was significantly correlated with anaemia. Plasma MTX level was significantly higher in patients with MTR A2756G G variants.MTHFR polymorphism played the main role in MTX toxicities. The pharmacokinetics of MTX was affected by MTR polymorphism. GGH mutation was mainly concerned with anaemia. Pharmacogenetic testing are recommended to optimise MTX therapy.

Association of ACE*(Insertion/Deletion) Variant with the Elevated Risk of Preeclampsia Among Gestational Women.

The renin-angiotensin-aldosterone system has an indispensable function in the uteroplacental circulation, placental growth, and blood pressure optimization. The angiotensin I converting enzyme (ACE) gene is a critical integrator for electrolyte balance, and water retention, along with inhibiting preeclampsia. The main goal of this pertaining study is to assess the contribution of ACE*(Ins/Del) variant with the susceptibility for preeclampsia with focus on the severity of the disease among gestational hypertensive women. This retrospective study included 225 participants [125 PE gestational women, and 100 normotensive healthy controls] matching with age, and geographical region. PE women classified into 82 early-onset PE women, accompanied with 43 late-onset PE women. Additionally, PE women categorized into 59 mild PE women, together with 66 severe PE women. The genotyping and characterization of ACE*(Ins/Del) variant were applied using the PCR technique. Our findings indicated higher frequency of the ACE*(Del/Del) genotype and ACE*(D allele) with elevated risk of preeclampsia compared to normotensive controls under recessive (OR = 2.09, and p-value = 0.007), and allelic (OR = 1.75, and p-value = 0.012) models. In addition, testing logistic regression revealed that the levels of endothelin-1 and malondialdehyde exposed significant difference for the ACE*(Del/Del) genotype among early-onset and late-onset PE women (p-value = 0.024, and 0.23, respectively). Furthermore, carriers of the ACE*(Del/Del) genotype observed statistically significant with lower sodium concentrations among severe PE women (p-value = 0.034). The ACE*(Del/Del) genotype and ACE*(D allele) were associated with increased risk preeclampsia among gestational women. Furthermore, early-onset PE and late-onset PE were correlated with endothelin-1 and malondialdehyde concentrations among Egyptian women.

Lactoferrin ameliorates carfilzomib-induced renal and pulmonary deficits: Insights to the inflammasome NLRP3/NF-κB and PI3K/Akt/GSK-3ß/MAPK axes.

AIMS: Carfilzomib, an irreversible proteasome inhibitor, has been increasingly used to treat multiple myeloma worldwide. However, case studies showed its treatment has been associated with cardiac, renal, and pulmonary deleterious effects. Lactoferrin is an iron-binding glycoprotein present in milk. It is a multifunctional protein with antimicrobial activity, antitumor, antioxidant, and anti-inflammatory effects. Thus, this study aimed to assess the protective effects of lactoferrin against carfilzomib-induced nephrotoxicity and pulmonary toxicity, in addition to identifying the possible underlying molecular mechanisms. MAIN METHODS: Mice were treated with lactoferrin (300 mg/kg/day) concomitantly with carfilzomib (4 mg/kg, i.p.) twice weekly for three weeks. Kidney and lung indices, serum creatinine, blood urea nitrogen (BUN), uric acid, kidney injury molecule-1 (KIM-1), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and histological examination were assessed. In addition, biochemical analyses of the inflammasome NLRP3/NF-κB and PI3K/Akt/GSK-3ß/MAPK axes were conducted. KEY FINDINGS: Treatment with lactoferrin decreased serum levels of creatinine, BUN, uric acid, KIM-1, ALP, AST, and LDH and reversed carfilzomib-induced histological changes in both kidney and lung. The inflammatory markers NLRP3, p65 NF-kB, caspases1, interleukin-1ß, and interleukin-18, as well as the MAPK signaling pathway, were significantly reduced in renal and pulmonary tissues of mice following lactoferrin administration. Moreover, lactoferrin significantly counteracted carfilzomib-induced reduced expression of pAkt and pGSK-3ß in both renal and pulmonary tissues. SIGNIFICANCE: The current study suggests lactoferrin might be a promising candidate for ameliorating carfilzomib-induced nephrotoxicity and pulmonary toxicity.

Actinidia deliciosa Extract as a Promising Supplemental Agent for Hepatic and Renal Complication-Associated Type 2 Diabetes (In Vivo and In Silico-Based Studies).

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However, the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway. Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic acid, and melezitose as components of kiwi extract that docked well with potential as effective natural products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the treatment of diabetic hepatorenal complications.

Association of HOTAIR gene rs920778 (C > T) and rs4759314 (A > G) polymorphism with breast cancer in Egyptian women.

BACKGROUND: Hox transcript antisense RNA (HOTAIR) is considered an oncogene associated with the initiation and progression of many malignancies. Previous studies have examined the connection between HOTAIR SNPs rs4759314 and rs920778 for breast cancer (BC), getting variable results in multiple ethnicities. Therefore, this study was designed to evaluate the connection between these two SNPs and disease vulnerability, clinic-laboratory, and hormonal parameters, featuring status associations with the BC risk in an Egyptian woman sample. METHODS AND RESULTS: In this case-control study, DNA was taken from the blood of 100 BC patients and 100 unrelated healthy Egyptian females. The characterization of rs4759314 was genotyped using the T-ARMS-PCR method and rs920778 using the SNP-RFLP technique for all participants. The frequency of the rs4759314 A > G variation revealed a statistically significant increase in BC risk with dominant (p = 0.013, OR = 1.592, 95% Cl = 1.105-2.293), co-dominant (p = 0.006, OR = 2.314, 95%Cl = 1.278-4.191) and overdominant (p = 0.002, OR = 2.571, 95% Cl = 1.430-4.624) genetic models. On the other hand, the rs920778 C > T polymorphism was not significantly associated with BC. ER/PR positivity with HER2 negativity was significantly associated with the AA genotype compared to the AG genotype. Otherwise, no significant associations between the two SNPs and clinical stage or hormonal features could be found. In conclusion, the rs4759314 A > G SNP in the HOTAIR gene is strongly associated with BC, which might warrant its determination among affected families for prevention and early treatment.

The Prevalence of MYD88 L265P and TNFAIP3 Mutations and Their Correlations with Clinico-Hematological Profile in Egyptian Patients with Diffuse Large B Cell Lymphoma.

BACKGROUND: Activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic active B-cell receptor signaling and a constitutive activation of the NF-KB pathway. MYD88 L265P mutation occurs as a driving force of NF-KB overactivity in ABC-DLBCL. Nonetheless, in cases of DLBCL, the MYD88 L265P mutation has not yet been investigated in association with the tumour necrosis factor alpha induced protein3 (TNFAIP3) mutation. OBJECTIVE: To investigate the frequency of MYD88 and TNFAIP3 mutations in DLBCL and their association to the clinico-hematological profile. MATERIAL AND METHODS: We used real-time polymerase chain reaction in order to search for MYD88 L265P and TNFAIP3 mutations in 100 DLBCL patients. RESULTS: MYD88 L265P In 20% of cases, the CT heterozygous genotype was discovered.  CT heterozygous genotype was more common in ABC type, stage IV, greater IPI groups, extra-nodal infiltration, and BM infiltration. It was also linked to a shorter OS. TNFAIP3 mutation GA heterozygous genotype was detected in 18% of the patients, with ABC-DLBCL subtype accounting for 77.8%. The GA heterozygous genotype was usually related with stage IV, extranodal infiltration, and a reduced life expectancy. CONCLUSION: MYD88 L265P and to lesser extent TNFAIP3 mutations are major mutations in ABC- DLBCL and may be predictive factors for poor OS in ABC- DLBCL patients.

Possible Protective Potency of Argun Nut (Medemia argun - An Ancient Egyptian Palm) against Hepatocellular Carcinoma in Rats.

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Medemia argun (MA) fruits have been found to possess proanthocyanidins (PACs), having antioxidant activity. Methods: Intraperitoneal (IP) diethyl nitrosamine (DENA; 200 mg/kg, once) and carbon tetra chloride (CCl4, 3 ml/kg/week, subcutaneously, for 6 weeks) induced HCC in rats. Animals groups: Group I; received vehicle (control). Group II; received MA seed extract, 100 mg/kg (twice/week) for 12 weeks, IP. Group III; received carcinogenic agents only. Group IV; received MA for two weeks before administration of DENA/CCl4 till the end of the experiment. The total period of the experiment was three months. Results: DENA and CCl4 induced HCC, elevated serum alpha-fetoprotein (AFP), liver size, weight, tissue lymphocytic infiltration, nuclear/cytoplasmic ratio, collagen fiber and polysaccharide deposition, cellular proliferation, excessive pro-apoptotic caspase-3 accumulation, disrupted apoptosis. MA prior to DENA/CCl4, significantly protected liver against cancer progression, indicated by serum enzymes, antioxidant markers(glutathione, nitric oxide, and depressed malondialdehyde contents) in the MA-pretreated group, compared to the HCC one, without apparent useful action on superoxide dismutase activity, enhanced apoptosis in liver, through increased casapase-3 expression. The HCC group showed decreased antioxidant defense and BAX/Bcl-2 ratio. Conclusions: This study assumes that MA has a chemo-preventive effect against hepatocarcinogenesis.

Urtica dioica extracts abolish scopolamine-induced neuropathies in rats.

Alzheimer's disease (AD) is characterized by alterations in monoamines, oxidative stress, and metabolic dysfunctions. We aim to assess the therapeutic impacts of roots or leaf extract from Urtica dioica (UD; stinging nettle) against scopolamine (SCOP)-induced memory dysfunction, amnesia, and oxidative stress in rats. Spatial memory was assessed by Y maze test. Tissue analyses of norepinephrine (NE), dopamine (DA), serotonin (5-HT), malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH, GSSG), AMP, ADP, and ATP were assessed by HPLC. mRNA levels of Tau and Hsp70 were estimated by PCR. UD extracts particularly nettle root (NR) significantly normalized the SCOP-induced memory deficits even more potent than sermion (SR) and donepezil (DON). Similarly, NR had potent therapeutic impacts on the levels of cortical and hippocampal monoamines e.g. DA, NE, and 5-HT. SCOP induced a dramatic oxidative stress as measured by MDA, NO, and GSSG levels; however, UD extracts showed significant anti-oxidative stress impacts. Additionally, UD extracts restored ATP levels and reduced the levels of AMP and ADP compared to SCOP-treated rats. Furthermore, cortical Tau and hippocampal Hsp70 were modulated by UD extracts particularly NR compared to the SCOP group. In conclusion, UD extracts particularly roots have potential therapeutic impacts against SCOP-induced neuroinflammatory and/or Alzheimer-like phenotype in rats.

Role of extracellular LncRNA-SNHG14/miRNA-3940-5p/NAP12 mRNA in colorectal cancer.

BACKGROUND: We aim to identify and analyze the expression of dyregulated RNAs in colorectal cancer (CRC). METHODS: We selected a panel of RNAs specific to CRC composed of Nucleosome Assembly Protein 1 Like 2 (NAP1L2) mRNA, LNCRNA SNHG14 small nucleolar RNA host gene 14 (LNCRNA SNHG14) and homo sapiens microRNA-3940-5p(hsa-miRNA-3940-5p) from genetic and epigenetic databases. Validation of the chosen RNAs was achieved by real time quantitative PCR in sera of patients with CRC, versus controls groups (benign lesions and healthy individual). RESULTS: We found that LLNCRNA SNHG14, hsa-miRNA-3940-5p and NAP1L2 mRNA had an excellent performance characteristics and more superior than CEA, and CA19.9 for differentiating CRC from controls. Combined expression of lncRNA SNHG14- hsa-miR-3940-5p and NAP1L2 mRNA had reached 100% sensitivity with accuracy 93%. Interestingly, serum hsa-miRNA-3940-5p could be an independent prognostic factor in CRC. CONCLUSION: The extracellular lncRNA SNHG14- hsa-miR-3940-5p - NAP1L2 mRNA may aid in CRC management.KEY MESSAGESThe extracellular RNAs provide a potential class of noninvasive biomarkers with high specificity, accuracy and stability for detection of CRC.We used insilico data analysis followed by qPCR for detection of differential NAP1L2 gene expression with the selected epigenetic regulators.Our data presented interesting biomarker panel (NAP1L2 gene, lncRNA-SNHG14 and hsa-miR-3940-5p) that may be potential for CRC diagnosis and prognosis.

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study.

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

Novel Targeted Nano-Parthenolide Molecule against NF-kB in Acute Myeloid Leukemia.

The targeted nano-encapsulation of anticancer drugs can improve drug delivery and the selective targeting of cancer cells. Nuclear factor kappa B (NF-kB) is a regulator for different biological responses, including cell proliferation and differentiation. In acute myeloid leukemia (AML), constitutive NF-κB has been detected in more than 50% of cases, enabling leukemic cells to resist apoptosis and stimulate uncontrolled proliferation. We evaluated NF-kB expression in bone marrow samples from 103 patients with AML using quantitative real time polymerase chain reaction (RT-PCR) and found that expression was increased in 80.5% (83 out 103) of these patients with AML in comparison to the control group. Furthermore, overexpressed transmembrane glycoprotein (CD44) on leukemic cells in comparison to normal cells is known to play an important role in leukemic cell engraftment and survival. We designed poly lactide co-glycolide (PLGA) nanoparticles conjugated with antiCD44 and encapsulating parthenolide (PTL), a nuclear factor kappa B (NF-kB) inhibitor, in order to improve the selectivity and targeting of leukemic cells and to spare normal cells. In vitro, in leukemic cell lines Kasumi-1, KG-1a, and THP-1, proliferation was decreased by 40% (** p < 0.01) with 5 µM PLGA-antiCD44-PTL nanoparticles in comparison to the same concentration of free PTL (~10%). The higher uptake of the nanoparticles by leukemic cells was confirmed with confocal microscopy. In conclusion, PLGA-antiCD44-PTL nanoparticles improved the bioavailability and selective targeting of leukemic cells, thus holding promise as a drug delivery system to improve the cure rate of AML.

Prognostic value of some inflammatory markers in patients with lymphoma.

Background: Lymphoma is a group of blood cell tumors which develop from lymphocytes. The main forms of lymphoma are Hodgkin lymphoma (HL) and non-HL (NHL). Cytokines may contribute to lymphoma and they are related to risk NHL and HL. Aim: Assessment of the serum level of certain inflammatory markers as complementary indicators to confirm diagnosis of lymphoma patients that may be subjected to more invasive biopsy methods. Method: The serum levels of interleukin (IL)-1ß (IL-1ß), IL-6, IL-10, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), and eotaxin were assessed by Bio-Plex Pro assays in 81 lymphoma patients and 44 NHL and 37 HL patients before and after chemotherapy treatment as well as 20 healthy persons as a control group. Results: Lymphoma patients showed significantly raised marker levels before treatment and significantly reduced levels related to pre-treatment and controls of post-treatment for most of the markers. MCP-1 reported the highest diagnostic accuracy. G-CSF significantly raised pre-treatment and TNF-α. MCP-1 significantly increased in post treated HL compared with NHL. In order to distinguish HL from NHL, G-CSF reported the highest diagnostic accuracy. NHL patients reported complete remission (CR) and those who reported stable disease (SD) and progressive disease (PD) represented 25% and 38% respectively compared with 16% and 27% of HL patients, while partial remission (PR) of HL patients were 56% compared with 36% of NHL patients. Conclusion: Most of the markers were significantly increased in pre-treatment but significantly decreased post-treatment. However, it was not considerably enough to get better prognosis of the disease. Elevated serum levels of inflammatory markers correlate with disease severity and low benefit from treatment.

Clinical significance of serum DRAM1 mRNA, ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 axis expression in malignant pleural mesothelioma.

AIM AND BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal cancer mainly caused by chronic exposure of asbestos. In this pilot study, we aimed to assess the expression of serum RNA-based biomarker panel exploring their clinical utility as diagnostic and prognostic biomarkers for MPM. METHODS: We have selected an MPM-specific RNA-based biomarker panel through bioinformatics analysis based on the integration of DNA damage regulated autophagy modulator 1 (DRAM1) and arylsulfatase A ( ARSA) gene expression with their epigenetic regulators microRNA ( miR-2053) and long noncoding RNA ( lncRNA-RP1-86D1.3). Then, quantitative real-time polymerase chain reaction (qPCR) validation in sera of 60 MPM patients, 20 chronic asbestos exposure patients, and 20 healthy volunteers was done. Lastly, the prognostic power of the selected panel was assessed. RESULTS: The expression of serum DRAM1 messenger RNA (mRNA), ARSA mRNA, hsa-miR-2053 and lncRNA-RP1-86D1.3 were positive in 78.3%, 90%, 85%, and 83.3% of MPM patients, respectively. The RNA-based biomarker panel was able to discriminate between MPM patients and controls with high accuracy and their combined sensitivity reached 100% for the diagnosis of MPM. Kaplan-Meier analysis showed that hsa-miR-2053 is an independent prognostic factor of MPM. CONCLUSION: Our preliminary data revealed that the chosen RNAs play an important role in driving MPM development and progression.

Urinary biomarkers for early detection of platinum based drugs induced nephrotoxicity.

BACKGROUND: Nephrotoxicity is a major hazard complicating the use of platinum based drugs (PBD), which can hinder using higher doses protocols to maximize the therapeutic gain. Shortage of serum creatinine level as an accurate biomarker for acute kidney injuries (AKI) necessitates searching for novel biomarkers with better sensitivity and specificity in patients on PBD. METHODS: In a prospective cohort design, 132 patients receiving PBD were selected for the study. AKI was diagnosed by continuous follow up of serum creatinine level according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 2012. Serum creatinine and urinary biomarkers (KIM-1, NGAL and cystatin C) was measured in the day of treatment and for 3 days after PBD cycle. RESULTS: AKI occurred in 35 patients (26.52% of patients). KIM-1, Cystatin C, and NGAL showed significant increase in samples collected in the day of AKI in comparison to their corresponding basal levels (P <  0.0001). In addition, significant increase in urinary levels of the biomarkers in samples collected 1 day before AKI in comparison to their basal levels (P <  0.0001, P <  0.0001, and P = 0.013 for KIM-1, NGAL and Cystatin C respectively). Furthermore KIM-1 data showed a significant increase 2 days before serum creatinine rise in comparison to the corresponding KIM-1 levels in patients who developed AKI (P = 0.001). CONCLUSIONS: Urinary KIM-1, Cystatin C and NGAL can predict PBD induced AKI in earlier stages than serum createnine. KIM-1 is the most sensitive biomarker for early detection of AKI in patients receiving PBD.

The Effect of Bone Marrow Mononuclear Cells on Lung Regeneration and Apoptosis in a Simple Model of Pulmonary Emphysema.

BACKGROUND: In severe chronic stages of emphysema the only treatment is lung transplantation. SO, an urgent need exists for the development of effective treatments. Stem cells therapy arises as a new therapeutic approach. AIM OF THE WORK: To investigate whether bone marrow mononuclar cells (BMMNCs) can promote lung regeneration and decrease apoptosis in lipopolysaccharide (LPS) induced pulmonary emphysema in C57Bl/6 mice. MATERIAL AND METHODS: 14 weeks old female mice (C57Bl/6), weighing around 25 g were used in this study. The mice were divided into 4 groups (10 in each group): group A: mice received no treatment, group B: mice received intranasal instillation of LPS with no further treatment, group C: mice received intranasal instillation of LPS then given a dose of BMMNCs and evaluated 21 days later and group D: the mice that received intranasal instillation of LPS then given a dose of Dulbecco's Modified Eagle's Medium (DMEM) and evaluated 21 days later. Imaging analysis was done using imagej program. To measure apoptotic index, Anti-caspase 3 polyclonal antibody staining was done. RESULTS: Analysis of the mean of airspace equivalent diameters (D0) and its statistical distribution (D1) for the different groups allowed to observe that group treated with BMMNCs (group C) showed the significant improvement in D0 and D1 than the group received LPS only (group B). Analysis of apoptotic index showed significant difference between BMMNCs treated group (group C) and that received LPS only (group B). CONCLUSIONS: BMMNCs effectively promote lung regeneration and reduction of apoptosis in pulmonary emphysema.

Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats.

BACKGROUND/AIMS: Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system of both acute and chronic renal changes. METHODS: This study used eighty Sprague-Dawley (SD) rats weighing 250-300g. They were assigned into four equal groups (each group n=20): (I) Negative control group, rats injected with single dose of 1 ml normal saline. (II) Positive control cisplatin, rats injected with a single dose of 5 mg/kg I.P in 1 ml saline. (III) Cisplatin and culture media group, rats injected with 0.5 ml of culture media single dose into the tail vein and (IV) Cisplatin and ADMSCs group, rats injected with a single dose of 0.5 ml of culture media containing 5 x10(6)ADMSCs into the tail vein one day after cisplatin administration. Each main group was further divided according to the timing of sacrifice into four subgroups (each subgroup n=5). Rats in the subgroup A were sacrificed after 4 days; subgroup B were sacrificed after 7 days; subgroup C were sacrificed after 11 days; and subgroup D were sacrificed after 30 days. Before sacrifice, 24 hrs.-urine was collected using a metabolic cage. Renal function was evaluated through blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Kidney tissue homogenate oxidative stress parameters, Malondialdehyde (MDA), Superoxide dismutase (SOD) and Glutathione (GSH) were determined. In addition, histopathological analysis for active injury, regenerative and chronic changes was performed. RESULTS: ADMSCs were characterized and their capability of differentiation was proved. Cisplatin induced a significant increase in plasma creatinine and tissue MDA and induced a decrease in SOD, GSH and creatinine clearance. ADMSCs attenuated these changes. Cisplatin resulted in prominent histopathological changes in the term of tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. ADMSCs significantly lowered the injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4 and limited fibrotic score at day 30. CONCLUSION: ADMSCs have both protective and regenerative abilities with consequent limitation of the development of renal fibrosis after the cisplatin induced acute tubular necrosis, largely through an anti-oxidative activity.