Aged garlic extract preserves beta-cell functioning via modulation of nuclear factor kappa-B (NF-κB)/Toll-like receptor (TLR)-4 and sarco endoplasmic reticulum calcium ATPase (SERCA)/Ca2+ in diabetes mellitus.

BACKGROUND: Peripheral insulin resistance and compromised insulin secretion from pancreatic ß-cells are significant factors and pathogenic hallmarks of diabetes mellitus (DM). NF-κß/TLR-4 and SERCA/Ca2+ pathways have been identified as potential pathways regulating insulin synthesis by preserving pancreatic ß-cell functioning. The current study aimed to evaluate the therapeutic effect of aged garlic extract (AGE) against DM in a streptozotocin (STZ)-induced rat model with particular emphasis on pancreatic ß-cell functioning. METHODS: AGE was characterized by gas chromatography-mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) to evaluate its physio-chemical characteristics followed by in-vitro anti-diabetic and antioxidant potential. This was followed by the induction of DM in laboratory animals for investigating the therapeutic action of AGE by evaluating the role of NF-κß/TLR-4 and the SERCA/Ca2+ pathway. The parameters assessed in the present experimental setup encompassed antioxidant parameters, metabolic indicators, insulin concentration, intracellular calcium levels, apoptotic markers (CCK-8 and Caspase Glo-8), and protein expression (P-62 and APACHE-II). RESULTS: AGE characterization by SEM, GC-MS, and X-ray diffraction (XRD) revealed the presence of phenylalanine, alliin, S-allylmercaptocysteine (SAMC), tryptophan, 1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid as major bioactive constituents of AGE. Metabolic studies, including intraperitoneal glucose tolerance test (IPGTT), revealed significantly lower blood glucose levels in the AGE group compared to the disease control group. In contrast, the intraperitoneal insulin tolerance test (ITT) exhibited no significant difference in insulin sensitivity between the AGE supplementation group and the DM control group. Interestingly, AGE was found to have no significant effect on fasting glucose and serum insulin levels. In contrast, AGE supplementation was found to cause significant hypoglycaemia in postprandial blood glucose and insulin levels. Importantly, AGE causes restoration of intracellular Ca2+ levels by modulation of SERCA/Ca2 functioning and inhibition NF-κB/TLR-4 pathway. AGE was found to interact with and inhibit the DR-5/ caspase-8/3 apoptotic complex. Furthermore, microscopic studies revealed degeneration and apoptotic changes in pancreatic ß-cells of the DM control group, while supplementation of AGE resulted in inhibition of apoptotic pathway and regeneration of pancreatic ß-cells. CONCLUSION: The current study suggests that AGE enhance glucose homeostasis by exerting their effects on pancreatic ß-cells, without ameliorating peripheral sensitivity. Moreover, AGEs promote an increase in ß-cell mass by mitigating the apoptosis of pancreatic ß-cells. These findings suggest that AGE could aid in developing a viable alternative therapy for diabetes mellitus (DM).

Computational Analysis of Deleterious nsSNPs in INS Gene Associated with Permanent Neonatal Diabetes Mellitus.

Insulin gene mutations affect the structure of insulin and are considered a leading cause of neonatal diabetes and permanent neonatal diabetes mellitus PNDM. These mutations can affect the production and secretion of insulin, resulting in inadequate insulin levels and subsequent hyperglycemia. Early discovery or prediction of PNDM can aid in better management and treatment. The current study identified potential deleterious non-synonymous single nucleotide polymorphisms nsSNPs in the INS gene. The analysis of the nsSNPs in the INS gene was conducted using bioinformatics tools by implementing computational algorithms including SIFT, PolyPhen2, SNAP2, SNPs & GO, PhD-SNP, MutPred2, I-Mutant, MuPro, and HOPE tools to investigate the prediction of the potential association between nsSNPs in the INS gene and PNDM. Three mutations, C96Y, P52R, and C96R, were shown to potentially reduce the stability and function of the INS protein. These mutants were subjected to MDSs for structural analysis. Results suggested that these three potential pathogenic mutations may affect the stability and functionality of the insulin protein encoded by the INS gene. Therefore, these changes may influence the development of PNDM. Further researches are required to fully understand the various effects of mutations in the INS gene on insulin synthesis and function. These data can aid in genetic testing for PNDM to evaluate its risk and create treatment and prevention strategies in personalized medicine.

Efficiency of natural oils as alternative adjuvants to mineral oils in inactivated avian influenza vaccine formulation.

1. The effectiveness of inactivated vaccines depends on selecting the suitable adjuvant for vaccine formulation. The potency of vaccines with low antigen content can be improved with the appropriate adjuvant. This could allow production of more doses and lower the production cost.2. This study evaluated the efficiency of vaccines prepared using oil extracted from natural sources including argan oil, almond oil, sesame seed oil, pumpkin oil, cactus oil and black seed oil as alternative adjuvants for improving the protection capacity of inactivated influenza virus vaccine as compared to commonly used mineral oils.3. Each vaccine formulation was evaluated for stability, safety and immunogenicity in chickens, as well as for reducing the viral shedding after challenge infection.4. The cactus, sesame and pumpkin seed oil-based vaccines were found to be potent and successfully induced the production of humoral immunity in vaccinated chickens.

Outcome of conventional radiotherapy in small centrally located tumours or lymph nodes: minimal toxicity, remarkable survival but challenging loco-regional control.

BACKGROUND: In peripheral lung tumours, stereotactic body radiotherapy (SBRT) is superior to conventional RT. SBRT has also shown high loco-regional control (LC) in centrally located tumours, but there is a high risk of severe toxicity. The STRICTSTARLung trial (NCT05354596) examines if risk-adapted SBRT for central tumours is feasible. In this study, we examined overall survival (OS), Disease-free survival (DSF), LC, and toxicity in patients with central tumours that could have been candidates for SBRT but received conventional RT. MATERIAL AND METHODS: Retrospectively, we evaluated 49 lung cancer patients that between 2008 and 2021 received RT (60-70Gy in 2 Gy fractions) for a solitary tumour or lymph node with a diameter <5cm located <2cm from the bronchial tree, oesophagus, aorta or heart. All tumours were pathologically verified; 30 were primary lung tumours (T1b-T4) and 19 were solitary lymph nodes (T0N1-N2). Chemotherapy was administered as concomitant (29) or sequential (4). OS and LC were analysed using Kaplan Meier. Cox proportional hazards model for OS and disease-free survival (DFS) was performed including tumour volume, histology, sex, T- vs N-site and chemotherapy. Toxicity was scored. RESULTS: In 42 patients, the tumour was located <1 cm to mediastinum. Median follow-up time was 44 months (range: 7-123). The median OS was 51 months. OS at 1-, 3- and 5-year was 88% (SE:5), 59% (SE:7) and 50% (SE:8). Loco-regional recurrences occurred in 16 patients resulting in 1-, and 3-year LC rates of 77% (SE:6) and 64% (SE:8). The majority occurred within 3 years after RT. Only stage showed significant impact on OS and DFS. No patients experienced grade 4-5 toxicity. Seven patients developed grade 3 toxicity (5 oesophageal stenosis, 2 pneumonitis). CONCLUSION: Conventional RT for patients with small central lung tumours or solitary lymph nodes is feasible. Median OS was 51 months, and toxicity was low with no grade 4-5 events.

2-(Benzhydryl sulfinyl)-N-sec-butylacetamide) isolated from fig augmented trastuzumab-triggered phagocytic killing of cancer cells through interface with Fcγ receptor.

The objective of the current study was to extract 2-(benzhydryl sulfinyl)-N-sec-butylacetamide), a novel compound from fig, and then determine its role in enhancing trastuzumab-triggered phagocytic killing of SKOV-3 cancer cells. In this study, Soxhlet was used to extract the compound from the mature and air-dried fig fruits. The production of the isolated extracts was enhanced by using polar and non-polar solvents. Several solvents, such as methanol, ethyl acetate, chloroform, and n-hexane, were used to isolate the effective compound 2-(benzhydryl sulfinyl)-N-sec-butylacetamide) from the organic layer. UV-spectroscopy, FT-IR, 1H-NMR, and 13C-NMR were applied to identify the purified compound. The in vitro and in vivo assays demonstrated that the 2-(benzhydryl sulfinyl)-N-sec-butylacetamide) can increase the activity of the phagocytic cells, via the interaction with FcY receptors, along with trastuzumab, and the pathway can use a model for the therapeutic strategy for effective treatment of ovarian cancer cells.

Folate-methotrexate loaded bovine serum albumin nanoparticles preparation: an in vitro drug targeting cytokines overwhelming expressed immune cells from rheumatoid arthritis patients.

The study planned to estimate biological parameters linked to rheumatoid arthritis (RA) patients, detecting the influence of MTX and biotherapy treatments on these parameters and synthesizing methotrexate bovine serum albumin nanoparticles linked to folate (FA-MTX-BSA NPs) to reduce the overwhelming expression of inflammatory cytokines. Inflammatory parameters showed significant increases in newly diagnosed and MTX-receiving groups while no changes were observed in the biotherapy-maintained group. MTX-loaded BSA nanoparticles were fabricated by the desolvation method and further linked to activated folic acid to obtain FA-MTX-BSA NPs. FA-MTX-BSA NPs were successfully characterized within the nanoscale range using different screening techniques. FA-MTX-BSA NPs showed an in vitro release in a sustained manner. The potential of MTX, MTX-BSA NPs, and FA-MTX-BSA NPs in inducing cytokine level reduction was detected. Significant decreases in interleukin- 1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were obtained in cultures treated with FA-MTX-BSA NPs compared to the untreated culture in a dose-dependent pattern. Furthermore, FA-MTX-BSA NPs comparing with MTX and MTX-BSA NPs exhibited a significant advanced effect in decreasing cytokines levels. Accordingly, the conjunction of BSA NPs and MTX linked to folate potentially reduced cytokines manifestation in RA.

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits / Efeitos protetores de Zizyphus oxyphyla em biomarcadores de soro relacionados ao fígado e rim em (CCl4) intoxicam rabbtis

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

O estudo teve como objetivo avaliar os efeitos terapêuticos das folhas metanólicas de Zizyphus oxyphyla (ZOX-LME) no fígado, rim e hematologia séricos, juntamente com outros parâmetros séricos em coelhos intoxicados com tetracloreto de carbono (CCl4). Os animais experimentais foram divididos em cinco grupos, seis coelhos em cada. Estes foram: grupo NC (controle normal), grupo TC (controle tóxico) e grupo ST, isto é, grupo administrado com silimarina na taxa de dose (50) mg / kg de peso corporal (PC). Grupo ET1 e grupo ET2 tratado com (ZOX-LME) na dose de 200 mg / kg de peso corporal e 400 mg / kg de peso corporal. A administração de CCl4 causou prejuízo significativo (P > 0,05) nas enzimas hepáticas séricas, fatores sanguíneos e outros índices séricos. O tratamento com (ZOX-LME) reduziu significativamente (P < 0,05) e normalizou os níveis de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP) e os índices hematológicos. Também foi observada redução significativa (P < 0,05) nas concentrações de creatinina, ureia, ácido úrico, nitrogênio ureico no sangue (BUN), albumina e glicose. Os níveis alterados de perfil lipídico e eletrólitos séricos (Ca, Mg, Cl, Na, K e P) foram significativamente (P < 0,05) mudando em direção aos níveis normais com a alimentação (ZOX-LME). Além disso, a ingestão de (ZOX-LME) causou melhora significativa nos níveis de GSH, GST e CAT, enquanto reduzia os níveis de TBARS, exibindo capacidade antioxidante. Também (ZOX-LME) mostrou inibição aumentada contra a eliminação percentual do radical livre 2, 2-difenila-1-picrilehidrazila (DPPH). Efeitos de normalização significativos (P < 0,05) foram observados com altas doses de 400 mg / kg de peso corporal de (ZOX-LME) e foram equivalentes aos grupos administrados com silimarina. O estudo histológico do fígado confirmou a atividade hepatoprotetora e curativa renal de (ZOX-LME).

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits

Abstract The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P 0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P 0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P 0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

Resumo O estudo teve como objetivo avaliar os efeitos terapêuticos das folhas metanólicas de Zizyphus oxyphyla (ZOX-LME) no fígado, rim e hematologia séricos, juntamente com outros parâmetros séricos em coelhos intoxicados com tetracloreto de carbono (CCl4). Os animais experimentais foram divididos em cinco grupos, seis coelhos em cada. Estes foram: grupo NC (controle normal), grupo TC (controle tóxico) e grupo ST, isto é, grupo administrado com silimarina na taxa de dose (50) mg / kg de peso corporal (PC). Grupo ET1 e grupo ET2 tratado com (ZOX-LME) na dose de 200 mg / kg de peso corporal e 400 mg / kg de peso corporal. A administração de CCl4 causou prejuízo significativo (P > 0,05) nas enzimas hepáticas séricas, fatores sanguíneos e outros índices séricos. O tratamento com (ZOX-LME) reduziu significativamente (P 0,05) e normalizou os níveis de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP) e os índices hematológicos. Também foi observada redução significativa (P 0,05) nas concentrações de creatinina, ureia, ácido úrico, nitrogênio ureico no sangue (BUN), albumina e glicose. Os níveis alterados de perfil lipídico e eletrólitos séricos (Ca, Mg, Cl, Na, K e P) foram significativamente (P 0,05) mudando em direção aos níveis normais com a alimentação (ZOX-LME). Além disso, a ingestão de (ZOX-LME) causou melhora significativa nos níveis de GSH, GST e CAT, enquanto reduzia os níveis de TBARS, exibindo capacidade antioxidante. Também (ZOX-LME) mostrou inibição aumentada contra a eliminação percentual do radical livre 2, 2-difenila-1-picrilehidrazila (DPPH). Efeitos de normalização significativos (P 0,05) foram observados com altas doses de 400 mg / kg de peso corporal de (ZOX-LME) e foram equivalentes aos grupos administrados com silimarina. O estudo histológico do fígado confirmou a atividade hepatoprotetora e curativa renal de (ZOX-LME).

Thorough design and pre-trial quality assurance (QA) decrease dosimetric impact of delineation and dose planning variability in the STRICTLUNG and STARLUNG trials for stereotactic body radiotherapy (SBRT) of central and ultra-central lung tumours.

INTRODUCTION: SBRT of central lung tumours implies significant risk of toxicity. We are initiating two phase II trials prescribing 56 Gy/eight fractions to PTV, allowing for dose escalation of GTV. We prioritize organs at risk (OAR) constraints over target coverage, making the treatment plans very sensitive to OAR delineation variations. The aim of this study is to quantify the dosimetric impact of contouring variations and to provide a thorough description of pre-trial quality assurance to be used in upcoming trials to provide consistent clinical care. MATERIALS AND METHODS: Delineation: Seven physicians delineated OAR in three rounds, with evaluations in-between. For each patient case, seven treatment plans, repeatedly using each of the OAR structure sets from the seven physicians, were made and compared to evaluate the dosimetric effect of delineation variability. Treatment planning: Treatment plans for seven cases were made at six departments in two rounds, with discussion in-between. RESULTS: OAR delineation variation between centres resulted in high variabilities in OAR dose for simulated plans and led to potential overdosage of the lobar bronchus (constraint: D0.03cc < 45 Gy), with maximum doses ranging between 58 Gy (first round), and 50 Gy (third round). For mediastinal tissue, the constraint (D0.03cc < 45 Gy) was violated for the majority of the delineations in all three rounds, with maximum doses of 84 Gy (first round), and 72 Gy (third round).For the treatment planning study, the range of the standard deviation for GTV mean dose was 12.8-18.5 Gy (first round) and 2.8-3.5 Gy (second round). CONCLUSIONS: Even small variations in OAR delineation led to high OAR overdosage. The study demonstrates the importance of having extensive QA procedures in place before initiating clinical trials on dose escalation in SBRT.

Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits.

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

A Novel Microfluidic Device for Blood Plasma Filtration.

The use of whole blood and some biological specimens, such as urine, saliva, and seminal fluid are limited in clinical laboratory analysis due to the interference of proteins with other small molecules in the matrix and blood cells with optical detection methods. Previously, we developed a microfluidic device featuring an electrokinetic size and mobility trap (SMT) for on-chip extract, concentrate, and separate small molecules from a biological sample like whole blood. The device was used to on-chip filtrate the whole blood from the blood cells and plasma proteins and then on-chip extract and separate the aminoglycoside antibiotic drugs within 3 min. Herein, a novel microfluidic device featuring a nano-junction similar to those reported in the previous work formed by dielectric breakdown was developed for on-chip filtration and out-chip collection of blood plasma with a high extraction yield of 62% within less than 5 min. The filtered plasma was analyzed using our previous device to show the ability of this new device to remove blood cells and plasma proteins. The filtration device shows a high yield of plasma allowing it to detect a low concentration of analytes from the whole blood.

A comparison of two methods for segmentation of functional volumes in radiotherapy planning of lung cancer patients.

BACKGROUND: In radiotherapy (RT) of lung cancer, dose to functional lung (FL) volumes segmented with two different methods (perfusion SPECT (Q-SPECT) and 4D-CT (4D) ventilation (V)) have been shown to correlate with the incidence of radiation pneumonitis (RP). This study aims to compare the FL volumes identified by both methods. MATERIAL AND METHODS: Thirty lung cancer patients had a 4D and Q-SPECT prior to treatment. Seventeen of these patients also had a ventilation SPECT (V-SPECT). FL sub-volumes were segmented automatically, using cut-off values. The volumes were compared in terms of overlap fraction (OF) relative to the minimal volume, and intersection fraction (IF) of the FL volume relative to the total lung volume (VLung). RESULTS: Cut-off values suggested in literature for Q-SPECT and 4D-V resulted in volumes differing in size by a median 18% [6%;31%], and a median OF and IF of 0.48 [0.23;0.70] and 0.09 [0.02;0.25], respectively. Segmenting volumes of comparable size of about 1/3 of VLung (FL-m(1/3), m = method) resulted in a median OF and IF of 0.43 [0.23;0.58] and 0.12 [0.06;0.19], respectively. Twenty-five patients (83%) had a reasonable overlap between FL-Q(1/3) and FL-4D-V(1/3) volumes, with OF values above 0.33. IF increased significantly (p = .036) compared to using fixed cut-off values. Similarly, volumes of comparable size of about 1/3 VLung were produced for V-SPECT, and FL-Q(1/3), FL-V(1/3), and FL-4D-V(1/3) were compared. The overlaps and intersections of FL-V(1/3) with FL-Q(1/3) volumes were significantly (p<.001) larger than the corresponding overlaps and intersections of FL-Q(1/3) with FL-4D(1/3) and FL-V(1/3) with FL-4D(1/3). CONCLUSION: The Q-SPECT and 4D-V methods do not segment entirely the same FL volumes. A reasonable overlap of the volumes along with the findings of other studies that both correlate to RP incidence, suggests that a combination of both volumes, e.g. using the IF, may be useful in RT treatment planning.

Local failure after radical radiotherapy of non-small cell lung cancer in relation to the planning FDG-PET/CT.

OBJECTIVES: Local recurrence (rec) in lung cancer is associated with poor survival. This study examined whether the pattern of failure is associated with the most PET avid volume in the planning-FDG-PET/CT scan (p-PET/CT). METHODS: 162 consecutive inoperable NSCLC patients (pts) receiving radiotherapy between January 2012 and April 2014 were reviewed. Radiotherapy was delivered in 2 Gy/fraction (5f/week) to a total dose of 60-66 Gy. Pts were followed with CT scans every third month. Patients with local rec as first event were analyzed. For the primary tumor (T) the overlap-fraction (OF) between 50% of SUVpeak on p-PET/CT and the volume of T-rec was calculated: OF = (SUVp50∩T-rec)/min(SUVp50, T-rec). Similarly for the GTV on the p-CT: OF = (GTV∩T-rec)/min(GTV, T-rec). OF was based on a rigid registration between p-PET/CT and rec-CT with PET guided delineation of T- rec. For lymph nodes (LN), the correlation between the location of treated-LN and the location of recurrence-LN was evaluated. RESULTS: 67 patients developed local rec. 51 pts had rec in T-site, 45 pts in LN-site. Due to anatomical changes, reliable registration between p-CT and rec-CT was only obtained in 26 pts with T-rec. The median OFSUVp50 was 52, 8% [range 26; 100%] and the median OFGTV was 80.5% [19.7; 100%]. Eleven pts had higher OFSUVp50 than OFGTV. LN-rec predominantly occurred in the station 2R (32%), 4R (46%), 7 (46%) and right hilum (36%). Pts with malignant LNs in station 4R or 7 on p-CT had a high risk of rec in these stations; 4R (55%) and 7 (83%). CONCLUSIONS: This study indicates that the most PET active volume on p-PET-CT is a driver for rec at T-site. LN-recurrences predominantly appear in station 2R, 4R, 7 and right hilum. Additional confirmatory studies regarding lymph node mapping and selective lymph node irradiation is needed.

Relationship among circulating anti-Müllerian hormone, insulin like growth factor 1, cadmium and superovulatory response in dairy cows.

The objectives of this study were 1. to determine the associations among circulating anti-Mullerian hormone (AMH), insulin like growth factor 1 (IGF1) and cadmium (Cd) concentrations of lactating Holstein cows at the time of superovulation and 2. to determine the effect of circulating AMH, IGF1 and Cd concentrations on the superovulatory response in Holstein dairy cows. Holstein cows (n = 30) were milked thrice daily and housed and fed in free stall barn as a separate group. All animals were synchronized for superovulation and flushed. Three blood samples for AMH, IGF1 and Cd analysis were collected prior to superovulation, at estrus and at the time of embryo collection. The concentrations of blood makers prior to superovulation were highly correlated to superovulatory response. Circulating concentrations of AMH, IGF1 prior to superovulation were negatively correlated to Cd concentrations (P < 0.05). There was no correlation between circulating concentrations of AMH and IGF1. The number of corpus luteum (r = 0.71), total embryo (r = 0.67), total transferable embryo (r = 0.51) and total grade 1 embryo (r = 0.5) were positively correlated to AMH concentrations (P < 0.05). There was a trend for negative correlation found between circulating cadmium concentrations and total grade 1 embryo yield (P < 0.1). When cows were classified into quartiles (Q) of circulating AMH concentration, number of corpus luteum, and total embryos, total transferable embryos and total grade 1 embryos yield was significantly different for AMH quartiles. The superovulatory response parameters evaluated were increased with increased AMH concentrations; particularly we observed a >2-fold difference between first and fourth AMH quartiles in total transferable embryo yield and total grade 1 embryo yield. In conclusion, circulating AMH concentration was strongly associated with superovulatory response. Measuring AMH before enrolling cows in superovulation programs will likely allow practitioners to improve numbers of embryos produced and, thereby, reduce costs per embryo produced.

Sodium Orthovanadate Inhibits Proliferation and Triggers Apoptosis in Oral Squamous Cell Carcinoma in vitro.

Sodium orthovanadate (SOV) is a general inhibitor of tyrosine phosphatases, a large family of enzymes that catalyze the removal of phosphate groups from tyrosine residues. SOV is commonly used in the laboratory to preserve the protein tyrosyl phosphorylation state of proteins under study. It has shown promising antineoplastic activity in some human cancer cell lines; this effect has not been fully investigated in head and neck squamous cell carcinoma. In this study, the effect of SOV on cell growth, proliferation, viability, and apoptosis was assessed in Cal27 cells, an oral squamous cell carcinoma (OSCC) cell line. SOV exhibited dose-dependent inhibition of cell growth and decrease in cell viability and colony formation. The IC50 values for treatment lasting 72 h and 7 days were 25 and 10 µM, respectively. The cytotoxic effect of the drug was associated with poly(ADP-ribose)polymerase cleavage detected by immunoblot. Flow cytometry of Cal27 cells stained with annexin V-FITC and propidium iodide showed a dose-dependent increase in apoptosis that reached approximately 40% at 25 µM SOV. These findings demonstrate that SOV has in vitro antiproliferative and proapoptotic effect on OSCC cells.

Synthesis, characterization and antibacterial activity of biodegradable films prepared from Schiff bases of zein.

Pure zein is known to be very hydrophobic, but is still inappropriate for coating and film applications because of their brittle nature. In an attempt to improve the flexibility and the antimicrobial activity of these coatings and films, Chemical modification of zein through forming Schiff bases with different phenolic aldhydes was tried. Influence of this modifications on mechanical, topographical, wetting properties and antimicrobial activity of zein films were evaluated. The chemical structure of the Schiff bases films were characterized by ATR-FTIR spectroscopy. The results indicate an improvement in mechanical properties with chemically modification of zein to form Schiff bases leading to a reduction in the elastic modulus. An increase in the elongation at break has been observed, but with slight influence on tensile strength. Plasticized zein films have similar initial contact angle (∼40°). An increase in reaction temperature and time increases film's affinity towards water. As shown by contact angle measurements, a noticeable relation was found between film composition and the hydrophilicity. Surface topography also varied by forming Schiff bases, becoming rougher than zein-based films. The antibacterial activities of zein and Schiff bases of zein-based films were investigated against gram-positive bacteria (Listeria innocua, Listeria monocytogenes, Bacillus cereus and Clostridium sporogenes) and gram-negative bacteria (Escherichia coli, Yersinia enterocolitica and Salmonella enterica). It was found that the antibacterial activity of the Schiff bases-based films was more effective than that of zein-based films.

Design, synthesis and evaluation of some novel pyrazoline derivatives as potential anti-inflammatory and antitumor agents.

A new series of pyrazoline derivatives was designed and synthesized with the objective of developing agents with anti-inflammatory activity together with chemoprevention of hepatobiliary malignancies. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced granuloma bioassay, using celecoxib as a reference drug. Ulcerogenic effect and acute toxicity profiles (ALD50) for the most active compounds were also determined. Compound 5c was proved to display anti-inflammatory activity better than celecoxib. Compounds 4b, 5d, 5c and 8 were found to be safer than indomethacin with respect to ulcerogenic effect and were well tolerated by the experimental animals with high safety margin (ALD50 >300 mg/Kg). Moreover, histopathological examination was carried out to detect the anti-inflammatory effect of the tested compounds on the livers of carrageenan-injected rats. On the other hand, compounds 4b, 4c, 4d, 5b, 5c, 5d, 6a, 6b, 6c, 6d, 8 and 9 were selected by the NCI to be evaluated for their anticancer activities but none has passed to the 5-dose assay. In addition, the ligand-receptor interactions of the most active compounds with COX-2 were investigated by performing docking studies using Molecular Operating Environment (MOE) version 2008.10.

Asymmetric dimethylarginine, arginine and homoarginine at 11-13 weeks' gestation and preeclampsia: a case-control study.

The aim of this study was to investigate whether the nitric oxide (NO) pathway is altered in pregnancies that develop preeclampsia (PE). This was a nested case-control study of screening for PE, in which plasma asymmetric dimethylarginine (ADMA), L-arginine and L-homoarginine were measured at 11(+0)-13(+6) weeks. In all, 75 pregnancies that developed PE, including 25 requiring delivery before 34 weeks (early PE), and 300 unaffected controls were included. L-arginine and L-homoarginine were measured by gas chromatography-mass spectrometry, whereas ADMA was measured by gas chromatography-tandem mass spectrometry. Multiple regression analysis was used to determine if any maternal characteristics or gestation were significant predictors. In the early-PE group, both L-arginine and L-homoarginine expected medians (MoMs) were significantly reduced (median, IQR: 0.85, 0.76-1.04 vs 0.98, 0.88-1.16, P=0.021 and 0.78, 0.65-0.96 vs 0.99, 0.77-1.31, P=0.006, respectively) but ADMA MoMs were not significantly different (P=0.599). In early PE, compared with controls, the ratios of ADMA to L-arginine MoMs and ADMA to L-homoarginine MoMs were increased (median, IQR: 1.19, 0.94-1.33 vs 1.01, 0.75-1.31, P=0.003 and 1.21, 0.93-1.61 vs 0.99, 0.87-1.16, P=0.012, respectively). There were no significant differences between late PE and controls in ADMA, L-arginine, L-homoarginine or their ratios. In conclusion, development of early PE is associated with altered NO metabolism and/or synthesis apparent from the first trimester.