In vitro study on the anticancer effects of oxalipalladium against PC3 human prostate carcinoma cells.

Prostate cancer is a common type of cancer in men with high incidence and mortality. Our aim was to investigate the effects of oxalipalladium (ox-Pd) on metastatic human prostate cancer PC3 cells and compare them with the effects of oxaliplatin (ox-Pt) (as an approved cancer drug). We synthesized ox-Pd through a new chemical method and used FT-IR, 1H NMR, 13C NMR, and MS analyzes to characterize it. The effects of ox-Pd on PC3 cells viability, apoptosis, cell cycle, migration, and gene expression were examined. Inhibition of topoisomerase IIα activity was investigated by pHOT1 plasmid relaxation and kDNA decatenation assays. Chemical tests showed ox-Pd with the correct composition and structure. For the first time, the exact fragmentation pathway of ox-Pd and its difference with ox-Pt was obtained by MS analysis. Ox-Pd significantly decreased PC3 cell viability with less/no toxicity effect on MHFB-1 normal skin fibroblasts. Wound scratch assay confirmed the strong anti-migratory activity of ox-Pd. According to flow cytometry analysis, this drug increased the number of PC3 cells in late apoptosis and decreased DNA replication and mitosis. Furthermore, pHOT1 plasmid relaxation and kDNA decatenation assays showed that ox-Pd strongly inhibited the catalytic activity of topoisomerase IIα. The expression of topoisomerase IIα, Bcl-2, P21, and survivin was decreased while the expression of Bax and p53 was increased under ox-Pd treatment. We provide the first evidence that ox-Pd exhibits more selective anticancer effects on PC3 cells compared to ox-Pt. Taken together, these data strongly suggest a therapeutic window for ox-Pd in cancer.

Assessment of the relationship between structural and functional tests in patients with idiopathic intracranial hypertension.

PURPOSE: To assess the relationship between structural and functional tests in mild and moderate idiopathic intracranial hypertension (IIH). METHODS: Patients with mild and moderate IIH and a control group were enrolled. Best-corrected visual acuity (BCVA), macular ganglion cell layer (MGCL) thickness, peripapillary retinal nerve fiber layer (pp RNFL) thickness, perimetric mean deviation (MD), and photopic negative responses (PhNR) of the electroretinogram were recorded. The associations between structural (pp RNFL and MGCL thickness) and functional (PhNR amplitude, MD and BCVA) parameters were assessed. RESULTS: 154 eyes from 78 subjects (74 eyes from IIH patients and 80 eyes from healthy subjects) were included in this comparative observational study. The MGCL thickness, VA, pp RNFL, and PhNR base-to-trough (BT) amplitude were significantly worse in moderate IIH. The BCVA and MD were associated with MGCL thickness only in moderate IIH. The relationship between MD and MGCL thickness started when MD fell below -5.7 dB. CONCLUSIONS: The association between functional and structural parameters varies between mild and moderate IIH. The MD and MGCL thickness outperformed in assessing disease severity in mild and moderate IIH, respectively. The association between MD and MGCL thickness could be considered in IIH severity categorization.

Metabolic engineering of Saccharomyces cerevisiae for production of ß-carotene from hydrophobic substrates.

ß-Carotene is a yellow-orange-red pigment used in food, cosmetics and pharmacy. There is no commercial yeast-based process for ß-carotene manufacturing. In this work, we engineered the baker's yeast Saccharomyces cerevisiae by expression of lipases and carotenogenic genes to enable the production of ß-carotene on hydrophobic substrates. First, the extracellular lipase (LIP2) and two cell-bound lipases (LIP7 and LIP8) from oleaginous yeast Yarrowia lipolytica were expressed either individually or in combination in S. cerevisiae. The engineered strains could grow on olive oil and triolein as the sole carbon source. The strain expressing all three lipases had ∼40% lipid content per dry weight. Next, we integrated the genes encoding ß-carotene biosynthetic pathway, crtI, crtYB and crtE from Xanthophyllomyces dendrorhous. The resulting engineered strain bearing the lipases and carotenogenic genes reached a titer of 477.9 mg/L ß-carotene in yeast peptone dextrose (YPD) medium supplemented with 1% (v/v) olive oil, which was 12-fold higher than an analogous strain without lipases. The highest ß-carotene content of 46.5 mg/g DCW was obtained in yeast nitrogen base (YNB) medium supplemented with 1% (v/v) olive oil. The study demonstrates the potential of applying lipases and hydrophobic substrate supplementation for the production of carotenoids in S. cerevisiae.

Synthesis of bifunctional cabbage flower-like Ho3+/NiO nanostructures as a modifier for simultaneous determination of methotrexate and carbamazepine.

Cabbage flower-like Ho3+/NiO nanostructure (CFL-Ho3+/NiO NSs) with significant electrocatalytic oxidation has been published for the first time. First, structure and morphology of CFL-Ho3+/NiO-NSs have been described by XRD, SEM, and EDX methods. Then, CFL-Ho3+/NiO-NSs have been applied as a modifier for simultaneous electrochemical detection of methotrexate (MTX) and carbamazepine (CBZ). Functions of the modified electrode have been dealt with through electrochemical impedance spectroscopy (EIS). It has been demonstrated that the electrode response has been linear from 0.001-310.0 µM with a limit of detection of 5.2 nM and 4.5 nM (3 s/m) through DPV for MTX and CBZ. Diffusion coefficient (D) and heterogeneous rate constant (kh) have been detected for MTX and CBZ oxidation at the surface of the modified electrode. Moreover, CFL-Ho3+/NiO-NS/GCE has been employed for determining MTX and CBZ in urine and drug specimens. Outputs showed the analyte acceptable recovery. Therefore, the electrode could be applied to analyze both analytes in drug prescription and clinical laboratories. Graphical abstract Electrochemical sensor based on bifunctional cabbage flower-like Ho3+/NiO nanostructures modified glassy carbon electrode for simultaneous detecting methotrexate and carbamazepine was fabricated.

Molecular epidemiology of lung cancer in Iran: implications for drug development and cancer prevention.

Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017. Of 1475 references identified through electronic searches, we reviewed the full text of 88 studies, and included 38 studies in the review. Potentially druggable NSCLC targets, which have been studied in Iran include EGFR, ALK, ERBB2, and KIT; but no studies were found, which examined the impact of MET, ROS1, BRAF, PIK3CA, and FGFR1 aberrations. We were able to identify some literature on DNA repair genes and xenobiotic metabolism, including TP53, TP63, ERCC2, XRCC2, SIRT1, PTEN, CYP1A1, CYP1B1, GSTT1, and GSTM1. We also found an increasing amount of research performed in relation to the tumor microenvironment and immune contexture, including CTLA4, MAGE, FOXP3, IFN-γ, and various interleukins, chemokines, and transcription factors; but did not identify any publication concerning the expression of PD-1/PD-L1 in lung cancer. Our survey of research performed in Iran has revealed a dearth of studies in topics, which are otherwise highly pursued in developed countries, but nevertheless, has begun to hint at a distinct biology of lung cancer in this part of the world.

Plasmon coupling between complex gold nanostructures and a dielectric substrate.

Intercoupling of an incident electric field in metal nanoparticles causes asymmetric distribution of surface charges, which eventuates in shifting of the surface plasmon resonance frequency. This feature can be used in tuning the surface plasmon resonance and controlling the light absorption in a desired wavelength. This work provides a theoretical study of the plasmonic properties of complex gold nanostructures on a dielectric substrate where the nanoparticles have different morphologies. For analysis, we have developed a discrete dipole approximation with surface interactions-z, which is the third version of the MATLAB-based DDA-SI toolbox. In this version, lower-upper decomposition of the interaction matrix is used as a preconditioning of the LSQR iterative solver. This method accelerates the DDA-SI calculations by decreasing the total number of iteration steps and decreases the relative residual to achieve more accurate results. In the analysis, nanostructures are assumed to be gold dimers, trimers, and quadrumers with different sizes and elongations of cubical or spherical geometries on a BK7 substrate. The results show that absorption spectra exhibit both red- and blueshifted plasmon resonances in array, depending on the particle shape and elongation. The cubic structure of gold array provides the highest absorption efficiency, while the spherical structures give wider bandwidth; the combination of these structures could be used to design a system with intended features. We demonstrate that the geometrical symmetry plays an important role in the plasmon resonance of gold arrays, and it is shifted when the symmetry of the array is broken.

Expression of VEGFR2 Ligand Binding Domain in Pichia pink™ 4 Cells and Evaluation of Its Interactions with VEGF-A165 Receptor Binding Domain.

Vascular endothelial growth factor A165 (VEGF-A165) and VEGF receptor 2 (KDR) are important mediators of angiogenesis. We aimed to express the soluble KDR ligand-binding domain (sKDR1-3) and evaluate its interaction with the VEGF-A165 receptor-binding domain (VEGFA165-RBD). sKDR1-3 DNA was designed and subcloned into pPinkα-HC plasmid. The cassette was transfected into the Pichia pink™ 4 genome by homologous recombination. We optimized the expression of sKDR1-3 under the induction of different methanol concentrations. VEGFA165-RBD was expressed in E. coli BL21 harboring pET28a( +)─VEGFA165-RBD vector under induction with IPTG with/without lactose. Interaction and biological activity of sKDR1-3 and VEGFA165-RBD were investigated by ELISA and anti-proliferation tests. sKDR1-3 migrated on SDS-PAGE gel as a 35-180 kDa protein due to glycosylation. The relative expression level of sKDR1-3 under 1% methanol was higher than 0.5% and 4% methanol induction. IPTG and cysteine were suitable for induction and refolding of VEGFA165-RBD. 25 ng sKDR1-3 and 20 ng VEGFA165-RBD showed strong binding. sKDR1-3 bound to VEGFA165-RBD and VEGF-A165 with dissociation constants of 0.148 and 0.2 nM, respectively. 4-10 nM concentrations of sKDR1-3 inhibited the proliferation of HUVE cells induced by 5 nM VEGFA165-RBD. In consideration, sKDR1-3 in the nanomolar concentration range, is a promising anticancer drug to inhibit angiogenesis.

Efficacy of body appreciation training on body image concerns in overweight adolescents.

Body image concern is one of the important issues in the field of overweight and the factors of failure in losing weight which is necessary to undergo intervention to increase the efficiency of sports and nutrition programs. This study aimed to analyze the efficacy of body appreciation training on body image concerns in overweight adolescents. It was a semi-experimental method with a pre-test and post-test design with a control group). The research community consisted of overweight girl adolescents who were referred to weight control and weight loss centers in Isfahan City in 2021. From the mentioned society, 30 adolescents were selected by targeted sampling method and assigned to two groups of 15 people, experiment and control. The experimental group received 9 sessions of 90-min body appreciation training. The control group was on the waiting list during this time. The research tool was the body image concern questionnaire of Littleton et al. (2005). Data analysis was done using SPSS-24 software and the covariance analysis method. The results showed that there is a significant difference between the two groups in the variable of concerns related to body image (P < 0.001); Also, the results showed that there is a significant difference between the two groups in the variables of dissatisfaction with appearance and interference in social functioning (P < 0.001). In this way, based on the results of this research, body appreciation training can be used to reduce concerns related to body image in overweight adolescents.

Epidemiology of injuries during Iran wheelchair basketball professional league: predictive risk factors and prevention strategies.

BACKGROUND: Very few studies have investigated athletes with disabilities during a long period of competitions, such as a professional league. Also, there are limited findings related to specific mechanisms and risk factors of injury, and prevention strategies in Wheelchair Basketball. Therefore, the objective of this study was to investigate the rate and characteristics of injuries in the 2021-2022 Iran Wheelchair Basketball League and present prevention strategies. METHODS: This retrospective study was conducted after the 2021-2022 (Mar 2021-Sep 2022) competition season. The sample size consists of 36 players, who were randomly selected among 129 players. All the data was processed using SPSS (version 21). RESULTS: 111 injuries were registered, equivalent to 132 per 100 players (95% CI: 100-180) and 8.16 Injuries per 1000 hours of athlete exposure (6.2-9.8). Also, 77.8% occurred during training and 22.2% in competitions. Most injuries affected the fingers and hands (35.13%), and shoulders (22.57%). The most common types of injuries were contusions (30.63%), laceration and skin lesion (23.42%), and muscle spasms (13.51%), in which, half of the injuries were slight (0-1 days), 27.8% (mild 4-7 days), and 22.2% moderate (8-28 days). Also, 66.9% of injuries were new, and 33.1% were recurrent. Most situations and actions leading to injury include quick wheelchair pushing (29.72%), the intense ball hitting (17.14%), and sudden stops or changes of direction of the wheelchair (12.63%). A multiple linear regression analysis (Enter method) demonstrated (R2 Adjusted=0.530) Wheelchair inappropriateness (P=0.015), lack of protective equipment (P=0.028), and previous injury (P=0.003) explained close to 55% of the injury rate. CONCLUSIONS: The injury rate during the league period was higher than the amounts reported from Paralympic games. Prevention strategies should be focused on rethinking athletes' pre-season readiness evaluation, return to play assessments and protection equipment technologies.

Polyhydroxyalkanoates (PHA): From production to nanoarchitecture.

Among many biodegradable and biocompatible biopolymers, polyhydroxyalkanoates (PHAs), generated by microorganisms, have highly attracted attention in various fields due to their unique physicochemical properties. So far, various types of progresses have been made in environmental and engineering fields by employing PHAs. Recently, employing PHAs for nanoarchitecture has become a newly emerging trend among researchers. The intrinsic nature of PHAs has dragged them towards fabrication of nanoparticles and nanocomposites. PHAs integration with nanoparticles has been vastly noted and applied in various areas such as drug delivery, antibacterial agents and bioengineering. Here, a brief review is given to how PHAs act and are produced by microorganisms, demonstrating their properties and finally, their most recent applications are discussed in nanoarchitecture and the ways they are manipulated in the fabrication of nanomaterials. This review can shed light on the exhaustive understanding of PHA capability in nanoarchitectural basics toward the development of advanced nanomaterials in many fields such as medicine, catalysis, sensor, and adsorbents.

The effect of Yarrowia lipolytical-asparaginase on apoptosis induction and inhibition of growth in Burkitt's lymphoma Raji and acute lymphoblastic leukemia MOLT-4 cells.

l-Asparaginase (l-asparagine amidohydrolase; E.C.3.5.1.1) as an anticancer agent is used to treat acute lymphocytic leukemia (ALL), Human Burkitt's lymphoma and non-Hodgkin's lymphoma. The commercial asparaginases are obtained from bacteria Erwinia chrysanthemi and Escherichia coli now which had many side effects. In this study, the effects of a novel l-asparaginase from yeast Yarrowia lipolytica was investigated on human ALL and Burkitt's lymphoma cell lines. The l-asparaginase causes metabolic stress, cytotoxicity, and apoptosis due to the arrest of the G0 cell cycle, the activation of caspase-3 and the modulation of mitochondrial membrane integrity. The RT-PCR analysis showed a significant increase in the pro-apoptosis genes such as Bax, Caspase-3, Caspase-8, Caspase-9 and p53 (P < 0.05) while the anti-apoptotic marker Bcl-2 was significantly decreased (P < 0.05). Furthermore, Y. lipolytical-asparaginase causes autophagy and increased ROS. The l-asparaginase has cytotoxic and anticancer effects higher than commercial asparaginase. In conclusion, Y. lipolytical-asparaginase shows interesting anticancer activity and it can be introduced as a new eukaryotic and therapeutic agent and strategy for ALL and Burkitt's lymphoma treatment after the in vivo and clinical experiments.

Noncovalent Immobilization of Yarrowia lipolytica Lipase on Dendritic-Like Amino Acid-Functionalized Silica Nanoparticles.

Immobilization of enzymes is a promising approach for the cost-effective application of enzymes. Among others, noncovalent but unleachable approaches for immobilization are one of the most favorable and crucial approaches. Herein, silica nanoparticles are modified by (3-aminopropyl)triethoxysilane (APTES) to generate amino-functionalized silica nanoparticles. Then, the amine functionalities are converted to bifunctional amino acid via post-modification that has zwitterionic properties. This nanostructure with the new functional theme is employed to immobilize Yarrowia lipolytica lipase at room temperature with no further post-modification or cross-linking. This immobilization method is further compared with the metal chelate-based immobilization approach on the same support. The biocatalytic activity of the immobilized lipase is examined under various conditions. The encapsulation of lipase through amino acid-functionalized silica nanoparticles exhibited enhanced stability for the immobilized lipase at higher temperatures and unneutral pHs.

DNA-binding affinity, cytotoxicity, apoptosis, cell cycle inhibition and molecular docking studies of a new stilbene derivative.

Stilbene derivatives have been found to possess promising anticancer activities against human cancer cell lines in vitro. In the present study, we have investigated cytotoxic, apoptosis induction and DNA binding activity of new stilbene derivative, (E)-1-(4-Chlorophenyl)-4,5-diphenyl-2-[4-(4-methoxystryl)phenyl]-1H-imidazol (STIM) on K562 chronic myeloid leukemia cell line. Via MTT assay STIM demonstrated cytotoxic activity against K562 cell line with IC50 value of 150 µM. Apoptosis, as the mechanism of cell death, was evaluated by morphological study and flow cytometric analysis. In vitro DNA binding property of STIM has been studied by vital spectroscopic techniques, which indicated that STIM interact with ctDNA through groove binding mode and binding constant (Kb) was estimated to be 6.9 × 104 M-1. Docking studies revealed that hydrophobic is the most important interaction in STIM-DNA complex, and that the ligand (STIM) interacts with DNA via groove binding mode and the bindiyspng energy was calculated as -13.37 kcal/mol. Taken together, the present study suggests that STIM exhibits anticancer effect on K562 cell line through the induction of apoptosis as well as cell cycle arrest at Sub-G1 phase and also can bind to double helix DNA in vitro.

Distribution of KRAS, DDR2, and TP53 gene mutations in lung cancer: An analysis of Iranian patients.

PURPOSE: Lung cancer is the deadliest known cancer in the world, with the highest number of mutations in proto-oncogenes and tumor suppressor genes. Therefore, this study was conducted to determine the status of hotspot regions in DDR2 and KRAS genes for the first time, as well as in TP53 gene, in lung cancer patients within the Iranian population. EXPERIMENTAL DESIGN: The mutations in exon 2 of KRAS, exon 18 of DDR2, and exons 5-6 of TP53 genes were screened in lung cancer samples, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) using PCR and sequencing techniques. RESULTS: Analysis of the KRAS gene showed only a G12C variation in one large cell carcinoma (LCC) patient, whereas variants were not found in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) cases. The Q808H variation in the DDR2 gene was detected in one SCC sample, while no variant was seen in the ADC and LCC subtypes. Variations in the TP53 gene were seen in all NSCLC subtypes, including six ADC (13.63%), seven SCC (15.9%) and two LCC (4.54%). Forty-eight variants were found in the TP53 gene. Of these, 15 variants were found in coding regions V147A, V157F, Q167Q, D186G, H193R, T211T, F212L and P222P, 33 variants in intronic regions rs1625895 (HGVS: c.672+62A>G), rs766856111 (HGVS: c.672+6G>A) and two new variants (c.560-12A>G and c.672+86T>C). CONCLUSIONS: In conclusion, KRAS, DDR2, and TP53 variants were detected in 2%, 2.17% and 79.54% of all cases, respectively. The frequency of DDR2 mutation is nearly close to other studies, while KRAS and TP53 mutation frequencies are lower and higher than other populations, respectively. Three new putative pathogenic variants, for the first time, have been detected in Iranian patients with lung cancer, including Q808H in DDR2, F212L, and D186G in coding regions of TP53. In addition, we observed five novel benign variants, including Q167Q, P222P and T211T in coding sequence, and c.560-12A>G and c.672+86T>C, in intronic region of TP53. Mutations of KRAS and DDR2 were found in LCC and SCC subtypes, respectively, whereas mutations of TP53 were seen in SCC and ADC subtypes with higher frequencies and LCC subtype with lower frequency. Therefore, Iranian lung cancer patients can benefit from mutational analysis before starting the conventional treatment. A better understanding of the biology of these genes and their mutations will be critical for developing future targeted therapies.

Interaction of Yarrowia lipolytica lipase with dithiocarbamate modified magnetic carbon Fe3O4@C-NHCS2H core-shell nanoparticles.

Fe3O4@C core-shell nanoparticles were modified by (3-aminopropyl)triethoxysilane (APTES) to generate amine functionality in the surface. Then, the amine functional groups were converted to dithiocarbamate via post-modification with carbon disulfide. This nanostructure with new functional property was used to immobilize lipase (obtained from Yarrowia lipolytica U6). Biocatalytic activity of the Fe3O4@C-NHCS-LIP was studied in this project. The interaction of lipase and support though dithiocarbamate binder was examined in the hydrolysis of p-nitrophenyl laurate. In this paper, support showed a unique feature in the immobilization of lipase by maintaining the lipase activity, raising the stability of lipase, and reusability.

Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.

The peptide hormone ghrelin is the endogenous ligand for the type 1a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant. GHS-R1a antagonism has therefore been proposed as a potential approach for obesity treatment. More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment. In our laboratories, piperidine-substituted quinazolinone derivatives were identified as a new class of small-molecule GHS-R1a antagonists. Starting from an agonist with poor oral bioavailability, optimization led to potent, selective, and orally bioavailable antagonists. In vivo efficacy evaluation of selected compounds revealed suppression of food intake and body weight reduction as well as glucose-lowering effects mediated by glucose-dependent insulin secretion.

Recent advances in the research and development of CB1 antagonists.

The worldwide prevalence of obesity has dramatically increased over the last 30 years, yet due to modest efficacy and side effects, current treatments for obesity are inadequate. Antagonists of the cannabinoid receptor type 1 (CB(1)) have emerged as a highly promising therapeutic strategy for obesity, with the 1,5-diaryl-pyrazole rimonabant (Sanofi-Aventis) being the most characterized and the furthest advanced agent in the clinic. This review focuses on recent publications (2002 to 2004) that describe the effects of CB(1) antagonists both on feeding behavior and in models of obesity, and the identification and characterization of new structure classes as CB(1) antagonists.

Evaluation of Antimicrobial Effects of Different Concentrations of Triple Antibiotic Paste on Mature Biofilm of Enterococcus faecalis.

Background and aims. Triple antibiotic paste (TAP) is widely used in endodontics for root canal disinfection, particularly in regenerative procedures. The aim of this in vitro study was to evaluate the antimicrobial effects of different concentrations of TAP at 1-, 2-, 3-, and 4-week intervals on mature Enterococcus faecalis biofilm. Materials and methods. A total of 287 extracted one-rooted human central incisors were infected with E. faecalis ATCC 29212 after removing the crown and preparation. The root canal space was filled with one of the 0.01-, 0.1-, 1-, 10-, 100-, and 1000-mg/mL concentrations of TAP or normal saline (control). The root canal dentin was sampled after 1, 2, 3, and 4 weeks. The dentinal shavings were cultured on Mueller-Hinton agar plates after serial dilutions. The classic colony-forming unit (CFU) counting technique was used to determine remaining bacterial counts. Data were analyzed by using the two-way ANOVA, post hoc Tukey tests and one-way ANOVA (P<0.05). Results. TAP completely eliminated E. faecalis biofilms at all the intervals at concentrations of 1000, 100, and 10 mg/mL, whereas 1-, 0.1-, and 0.01-mg/mL TAP resulted in significant reduction of CFU means compared with the control group. There were no statistically significant differences between the four time intervals. Conclusion. Use of lower concentrations of TAP at short term could eradicate E. faecalis biofilm and decrease high-concentration side effects.

A Three-rooted Mandibular Second Premolar: A Case Report.

Presence of extra roots and canals should be considered before initiation of root canal treatment for the success of endodontic treatment. A mandibular second premolar with three separate roots is very rare and its prevalence has been reported to be around 0.1%. This case report explains non-surgical endodontic treatment of a mandibular second premolar with three separate roots and three separate mesiobuccal, midbuccal, and lingual canal orifices. Close attention to anatomic variations, thorough radiographic examinations, thorough evaluation of the pulp chamber floor, and use of magnifying and optical devices have been recommended for the success of endodontic treatment of mandibular second premolars with complicated root canal system anatomy.

Identification of selective neuropeptide Y2 peptide agonists.

Activation of the NPY2 receptor to reduce appetite while avoiding stimulation of the NPY1 and NPY5 receptors that induce feeding provides a pharmaceutical approach to modulate food intake. The naturally occurring peptide PYY(3-36) is a nonselective NPY1, NPY2, and NPY5 agonist. N-terminal truncation of PYY to abrogate affinity for the NPY1 and NPY5 receptors and subsequent N-terminal modification with aminobenzoic analogs to restore NPY2 receptor potency results in a series of highly selective NPY2 receptor peptide agonists.