Search

Convolvulus arvensis L. is rich in phenolic compounds and traditionally used to treat wounds, skin ulcer, and inflammation. The current study is aimed at scientifically potentiating its traditional wound healing use. The methanolic extract of C. arvensis stem (CaME) was analyzed for HPLC and GC-MS analyses. The binding modes of active compounds were investigated against protein targets glycogen synthase kinase-3β (GSK-3β), transforming growth factor-beta (TGF-β), c-myc, and β-catenin by molecular docking followed by molecular dynamic simulations which revealed some conserved mode of binding as reported in crystal structures. The antioxidant potential of CaME was evaluated by in vitro methods such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, and ferric reducing power assays. Ointment formulations of 10 and 20% CaME were applied topically and evaluated for wound healing potency against the excisional wound on the skin of Wistar rats. Gentamycin (0.1%) served as standard therapy. The healing process was observed for 20 days in the form of wound size and epithelialization followed by histopathological evaluation of the wound area. Chemical characterization showed the presence of 7-hexadecenoic acid, 2-hexadecylicosan-1-ol, quercetin, gallic acid, ferulic acid, and other compounds. The plant extract exhibited significant in vitro antioxidant activity. The animals treated with 10% ointment showed moderate healing, whereas the treatment with 20% CaME revealed healing potential comparable to the standard 0.1% gentamycin as coevidenced from histopathological evaluation of skin. The study corroborates promising potential of C. arvensis on the healing of wounds, which possibly will be attributed to its antioxidant activity, fatty acids, quercetin, and gallic and caffeic acids, and binding potential of its phytoconstituents (phenolic acids) with wound healing targets.

The acute promyelocytic leukemia (APL) driver ZBTB16/RARα is generated by the t(11;17) (q23;q21) chromosomal translocation, which is resistant to combined treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) or conventional chemotherapy, resulting in extremely low survival rates. In the current study, we investigated the effects of hyperthermia on the oncogenic fusion ZBTB16/RARα protein to explore a potential therapeutic approach for this variant APL. We showed that Z/R fusion protein expressed in HeLa cells was resistant to ATO, ATRA, and conventional chemotherapeutic agents. However, mild hyperthermia (42 °C) rapidly destabilized the ZBTB16/RARα fusion protein expressed in HeLa, 293T, and OCI-AML3 cells, followed by robust ubiquitination and proteasomal degradation. In contrast, hyperthermia did not affect the normal (i.e., unfused) ZBTB16 and RARα proteins, suggesting a specific thermal sensitivity of the ZBTB16/RARα fusion protein. Importantly, we found that the destabilization of ZBTB16/RARα was the initial step for oncogenic fusion protein degradation by hyperthermia, which could be blocked by deletion of nuclear receptor corepressor (NCoR) binding sites or knockdown of NCoRs. Furthermore, SIAH2 was identified as the E3 ligase participating in hyperthermia-induced ubiquitination of ZBTB16/RARα. In short, these results demonstrate that hyperthermia could effectively destabilize and subsequently degrade the ZBTB16/RARα fusion protein in an NCoR-dependent manner, suggesting a thermal-based therapeutic strategy that may improve the outcome in refractory ZBTB16/RARα-driven APL patients in the clinic.

Polycystic ovarian syndrome (PCOS) is an heterogenous, endocrine, metabolic, and multidisciplinary disorder of reproductive-aged females that aggravates insulin resistance, hyperandrogenism, obesity, menstrual irregularities, and infertility. Bitter melon is consumed as vegetable in various parts of the world. The purpose of this study was to provide the rationale for the folkloric uses of bitter melon (Momordica charantia L.) in reproductive abnormalities. HPLC analysis of standardized aqueous methanolic extract of bitter melon revealed the presence of various phytochemicals such as quercetin, gallic acid, benzoic acid, chlorogenic acid, syringic acid, p-coumaric acid, ferulic acid, and cinnamic acid. Twenty-five Swiss albino adult female rats (120–130 g) were acquired and divided into two groups (5 + 20). Letrozole (1 mg/kg p.o.) was used for four weeks to induce PCOS in twenty rats. Disease induction was confirmed by vaginal smear cytology analysis under the microscope. Animals were further divided into four groups, with one group as PCOS group, and the remaining three are treated with standardized extract of bitter melon (500 mg/kg p.o.), bitter melon plus metformin (500 mg/kg p.o.), and metformin alone for the period of next four weeks. After four weeks, the rats were euthanized at diestrus stage. Ovaries of the experimental animals were removed and fixed in 10% buffered formalin, and blood samples were obtained from direct cardiac puncture and stored. Ovaries histopathological analysis showed cystic follicles (9–10) in PCOS group, while, in all the treatment groups, we found developing and mature follicles. Similarly, hormone analysis showed significant ( p < 0.001 ) reduction of LH surge, insulin, and testosterone levels and improvement in FSH levels. Lipid profile and antioxidant enzymes status were also significantly ( p < 0.001 ) improved. In conclusion, the study validates the bitter melon potential as an insulin sensitizer and ovulation enhancer and authenticates its potential in PCOS management.

Parkinson’s disease (PD) is a complex, age-related neurodegenerative disease that causes neuronal loss and dysfunction over time. An imbalance of redox potential of oxidative stress in the cell causes neurodegenerative diseases and dysfunction of neurons. Plants are a rich source of bioactive substances that attenuate oxidative stress in a variety of neurological disorders. The aim of the present study was to evaluate the Prunus armeniaca L. methanolic extract (PAME) for anti-Parkinson activity in rats. PD was induced with haloperidol (1 mg/kg, IP). The PAME was administered orally at 100, 300, and 800 mg/kg dose levels for 21 days. Behavioral studies (catalepsy test, hang test, open-field test, narrow beam walk, and hole-board test), oxidative stress biomarkers (SOD, CAT, GSH, and MDA) levels, neurotransmitters (dopamine, serotonin, and noradrenaline) levels, and acetylcholinesterase activity were quantified in the brain homogenate. Liver function tests (LFTs), renal function tests (RFTs), complete blood count (CBC), and lipid profiles were measured in the blood/serum samples to note the side effects of PAME at the selected doses. Histopathological analysis was performed on the brain (anti-PD study), liver, heart, and kidney (to check the toxicity of PAME on these vital organs). Motor functions were improved in the behavioral studies. Dopamine, serotonin, and noradrenaline levels were significantly increased ( P < 0.001 ), whereas the level of acetylcholinesterase was decreased significantly ( P < 0.001 ). The levels of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were increased, while malondialdehyde (MDA) and nitrite levels were decreased in the PAME-treated groups significantly compared with the disease control group, hence reducing oxidative stress. The incidence of toxicity was determined by biochemical analysis of LFT and RFT biomarkers testing. The histopathological analysis indicated that neurofibrillary tangles and plaques decreased in a dose-dependent manner in the PAME-treated groups. Based on the data, it is concluded that PAME possessed good anti-Parkinson activity, rationalizing the plant’s traditional use as a neuroprotective agent.

Seerat Mehdi,1 Fiaz-ud-Din Ahmad,1 Arslan Hussain Lodhi,1 Umair Khurshid,2 Ahmed Awais Khalid,1 Sheikh Safeena Sidiq,1 Liaqat Hussain,3 Mirza Shaharyar Baig1 1Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 3Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, PakistanCorrespondence: Fiaz-ud-Din Ahmad, Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Khawaja Fareed Campus, Railway Road, Bahawalpur, 63100, Pakistan, Tel +92-320-8402376, Email fiaz.ahmad@iub.edu.pkAim: Liver regulates metabolism of biomolecules and injury of liver causes distortion of metabolic functions. This injury may be oxidative or inflammatory induced by numerous factors including alcohol, pathogens and xenobiotics. This scientific study was planned to investigate the anti-inflammatory and anti-oxidant potential of p-coumaric acid (p-CA) on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN) induced liver injury.Methods: DPPH analysis, reducing power assay and HPLC analysis were performed during in-vitro studies of p-CA. Similarly, in-vivo experiments were performed using Wistar Albino rats. Normal control and intoxicated group received (5mL/kg normal saline p.o), standard treatment groups received ascorbic acid (100mg/kg p.o) and silymarin (25mg/kg p.o), while p-CA treatment groups received (100mg/kg p.o) for 28-days. After completion of 28-days, LPS/D-GalN injection (300 mg D-GalN/kg and 10 μg LPS/kg i.p.) was given at 6th, 12th and 24-hours to all groups except normal control group. Animals were sacrificed; serum and liver samples were harvested and subjected to biochemical and histological examinations, respectively.Results: The results revealed that p-CA possess strong antioxidant activity. Increased levels of leukocyte infiltration (TLC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), lipid panel (eg TG, TC, LDL-C, VLDL-C), whereas decreased HDL-C levels noticed in LPS/D-GalN groups as compared to normal control groups. Pro-Inflammatory markers (eg TNF-α, IL-6, IL-1β) and lipid peroxidation marker, eg malondialdehyde (MDA) increased while superoxide dismutase (SOD) and reduced glutathione (GSH) levels were decreased significantly in groups treated with LPS/D-GalN. ANOVA with Bonferroni post hoc analysis was used for statistical analysis of. H&E staining was done to assess architectural abnormalities among liver cells.Conclusion: In conclusion, p-CA could ameliorate LPS/D-GalN induced hepatic injury via regulation of immune responses, liver function enzymes, lipid profile, oxidative stress and pro-inflammatory markers.Keywords: p-coumaric acid, lipopolysaccharide, D-galactosamine, oxidative stress, inflammation

Natural products are known to control diabetes and its associated complications. Leaves of Hedera nepalensis are used to cure diabetes in the folklore system of medicines. The present study was designed to evaluate the in vivo antidiabetic and wound healing potentials of ethanol extract of Hedera nepalensis. Ethanolic extract (Hn.Cr) was prepared by maceration and was chemically characterized by HPLC methods. Antioxidant and antimicrobial properties were assessed in three in vitro models. Toxicity profile of Hn.Cr was evaluated in acute toxicological studies. Alloxan-induced diabetes model was used to access the antidiabetic attributes of Hn.Cr. Excision wound healing model was used to access the wound healing potential of Hn.Cr in alloxan-induced diabetic rats. HPLC analysis of Hn.Cr revealed the presence of phenolic and flavonoids compounds. Data of in vitro antioxidant assays showed that Hn.Cr has moderate radical scavenging potential. In vitro antimicrobial testing results revealed that Hn.Cr was active against bacterial strains (Gram +ve and Gram -ve) while no activity was observed against fungal strains used in the current study. Acute toxicity study results showed that extract was safe up to the dose of 5000 mg/kg. In vivo antidiabetic study revealed that Hn.Cr significantly (p

Background: Raphanus sativus is traditionally used as an anti-inflammatory agent. Objectives: The current study was designed to explore the in vivo anti-inflammatory and antiangiogenic properties of Raphanus sativus seeds oil. Methods: Cold press method was used for the extraction of oil (RsSO) and was characterised by using GC-MS techniques. Three in vitro antioxidant assays (DPPH, ABTS and FRAP) were performed to explore the antioxidant potential of RsSO. Disc diffusion methods were used to study in vitro antimicrobial properties. In vivo anti-inflammatory properties were studied in both acute and chronic inflammation models. In ovo chicken chorioallantoic membrane assay was performed to study antiangiogenic effects. Molecular mechanisms were identified using TNF-α ELISA kit and docking tools. Results: GC-MS analysis of RsSO revealed the presence of hexadecanoic and octadecanoic acid. Findings of DPPH, ABTS, and FRAP models indicated relatively moderate radical scavenging properties of RsSO. Oil showed antimicrobial activity against a variety of bacterial and fungal strains tested. Data of inflammation models showed significant (p < 0.05) anti-inflammatory effects of RsSO in both acute and chronic models. 500 mg/kg RsSO halted inflammation development significantly better (p < 0.05) as compared with lower doses. Histopathological evaluations of paws showed minimal infiltration of inflammatory cells in RsSO-treated animals. Findings of TNF-α ELSIA and docking studies showed that RsSO has the potential to down-regulate the expression of TNF-α, iNOS, ROS, and NF-κB respectively. Moreover, RsSO showed in vivo antiangiogenic effects. Conclusion: Data of the current study highlight that Raphanus sativus seeds oil has anti-inflammatory, and antiangiogenic properties and can be used as an adjunct to standard NSAIDs therapy which may reduce the dose and related side effects.

Jet impingement finds an important role in several industrial applications which require high thermal-hydraulic performance of heat exchange systems. The self-exciting sweeping jets produced by fluidic oscillators provide superior thermal and hydraulic performance as compared to plain jets. The fluidic oscillator increases the jet impingement area on the target surface by maintaining a steady and controlled oscillatory flow. The continuous advancements in the design improvement of fluidic oscillators have led to further enhancements of heat and fluid flow characteristics. In this context, double feedback fluidic oscillators have shown promising jet flow control features and jet impingement cooling characteristics. Therefore, the current study has been devoted to analyzing and assessing the recent research progress in design improvements of double feedback fluid oscillators and the augmentation of thermal-hydraulic characteristics of impinging sweeping. Moreover, the variations in the heat transfer and hydraulic performance of impinging jets for different shapes of target surfaces have been comprehensively examined. In the end, research gaps for future work have been highlighted.

Dietary fiber is getting attention these days due to its tendency to improve the reproductive performance in human beings. Sodium alginate (SA) is one of the natural dietary fibers. The present study aimed to evaluate the effect of SA on serum insulin, blood sugar, lipid profile, estrogen and testosterone in polycystic (PCOS) females. A single

Polycystic ovarian syndrome is a multidisciplinary endocrinopathy of reproductive-aged women that provokes insulin resistance, hyperandrogenism, cardiovascular problems, obesity, and menstrual complications. The present study was designed to investigate the effectiveness of ethanolic extract of

Polycystic ovarian syndrome is a multidisciplinary endocrinopathy of reproductive-aged women that provokes insulin resistance, hyperandrogenism, cardiovascular problems, obesity, and menstrual complications. The present study was designed to investigate the effectiveness of ethanolic extract of Fagonia indica in letrozole-induced PCOS young adult female rats. HPLC was carried out to find the phenolic and flavonoid content of the ethanolic extract of Fagonia indica. Twenty-five female rats were taken and initially divided into two groups: group I (control group) and group II (PCOS group). PCOS was induced by letrozole given orally by gavage. Body weight was recorded weekly and vaginal cytology was analyzed daily. After induction of disease, the PCOS group is further divided into four groups (n = 5): group II (positive control with PCOS), group III (metformin 20 mg/kg treated group), group IV (ethanolic extract of Fagonia indica 500 mg/kg treated group), and group V (metformin plus Fagonia extract). At the end of experimental period, the blood sample of each rat was collected and serum was separated by centrifugation. Afterwards hormonal analysis, lipid profile and liver functioning tests were performed. Ovaries were removed and preserved for histopathological findings while the liver of each rat was stored for the determination of antioxidant potential assessment. Fagonia indica was found to possess quercetin as one of the major flavonoid phytoconstituents. The plant extract exhibited its beneficial effects by restoring hormonal balance, lipid profile, and liver functioning markers. Treatment with F. indica reduced body weight, resolved ovarian cysts, and showed positive effects on follicular growth. Treatment with plant also increased the levels of antioxidant enzymes. This study validates the potential of Fagonia indica for the amelioration of metabolic, as well as, hormonal disturbances that occurred in PCOS.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), severe form of ALI, are characterized by overwhelming of lung inflammation, and no treatment is currently available to treat ALI/ARDS. Cigarette smoke (CS) is one of the prime causes to induce ALI/ARDS via oxidative stress. Despite extensive research, no appropriate therapy is currently available to treat ALI/ARDS. Hence, new potential approaches are needed to treat ALI/ARDS. Consequently, this project was designed to explore the protective effects of verapamil against CS-induced ALI by in vivo and in vitro method. In vivo data obtained from respiratory mechanics, pulmonary morphometric analyses and lung histopathology revealed that verapamil dose-dependently and strikingly decreased the lung weight coefficient, attenuated the albumin exudation into lungs, minimized the infiltration of macrophages and neutrophils into lungs, reduced the pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and keratinocyte chemoattractant (KC)) production, and improved the hypoxemia and lung histopathological changes. Similarly, verapamil also reduced the production of TNF-α, IL-6 and KC from cigarette smoke extract (CSE)-stimulated RAW 264.7 macrophage. Importantly, verapamil dose-dependently and remarkably suppressed the CS-induced oxidative stress via not only reducing the myeloperoxidase (MPO) activity of lungs, total oxidative stress (TOS) and malondialdehyde (MDA) content in the lungs and supernatant of RAW 264.7 macrophage but also improving total antioxidant capacity (TAC) and superoxide dismutase (SOD) production. Finally, verapamil strikingly decreased the NF-κB expression both in in vivo and in vitro models. Hence, verapamil has positive therapeutic effects against CS-induced ALI via suppressing uncontrolled inflammatory response, oxidative stress and NF-κB p65 signaling.

The aims and objectives of the study were to evaluate the antiParkinson’s (PD) potential of B cernua (BCE). B cernua (Poir.) Müll. Arg. (B cernua) is a member of the Phyllanthaceae family. HPLC revealed the presence of various phytochemicals. Study was conducted for 40 days. After PD induction by paraquat behavioural studies were carried out. Biochemical parameters such as DPPH, NO-scavenging, Ferrous reducing power, MDA, GSH, CAT, SOD, acetylcholinesterase (AChE), neurotransmitter estimation and TNF-α and IL-6 levels were determined. DPPH, NO-scavenging and Ferrous reducing power assays showed 78.02%, 48.05% and 71.45% inhibitions, respectively. There was significant improvement in motor functions and coordination in a dose-dependent manner (50 < 250 < 500 mg/kg) in PD rat model. Biochemical markers; SOD, CAT, GPx and GSH showed significant restoration ( P < .001) while MDA showed significant decrease ( P < .05). The AChE level was significantly reduced ( P < .05) at 500 mg/kg while neurotransmitters were significantly improved ( P < .001) in a dose-dependent fashion. The ELISA results showed significant ( P < .001) down-regulation of IL-6 and TNF-α level. In conclusion, it is suggested that BCE has the potential to reduce the symptoms of PD.

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein–associated cancers by hyperthermia. Significance: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers. See related commentary by Wu et al., p. 300.

PLZF-RARα is the second most frequent variant acute promyelocytic leukemia (APL) fusion protein that ranks after PML-RARα in APL. However, PLZF-RARα is resistant to current front line APL treatments including all transretinoic acid (ATRA), arsenic trioxide (ATO), and chemotherapy (i.e., Idarubicin). Herein, we for the first time report that phenylarsine oxide (PAO) could effectively induce PLZF-RARα variant fusion protein degradation through ubiquitin proteasome degradation pathway by apoptosis, which indicates that PAO might be a potential candidate for the treatment of PLZF-RARα variant APL. Given that, this study highlights the potential benefit of arsenic-organometallic compound PAO in APL treatment.

Jet impingement is considered to be an effective technique to enhance the heat transfer rate, and it finds many applications in the scientific and industrial horizons. The objective of this paper is to summarize heat transfer enhancement through different jet impingement methods and provide a platform for identifying the scope for future work. This study reviews various experimental and numerical studies of jet impingement methods for thermal-hydraulic improvement of heat transfer surfaces. The jet impingement methods considered in the present work include shapes of the target surface, the jet/nozzle–target surface distance, extended jet holes, nanofluids, and the use of phase change materials (PCMs). The present work also includes both single-jet and multiple-jet impingement studies for different industrial applications.

Antimony (Sb) belongs to the same group as arsenic (As) in the periodic table, and both share similar characteristics. However, Sb2O3 (SbIII) has no methylation capacity, unlike arsenic trioxide (As2O3). In the present study, we determined the effect of SbIII on NB4 cells and found that antimony could induce PML-RARα fusion protein degradation, reorganization of PML-NBs, and NB4 cell differentiation with low cytotoxicity. On the other hand, zinc finger motifs in PML protein are considered to be a key target binding site for arsenic-induced PML-RARα protein degradation. Interestingly, antimony and arsenic lost their ability to degrade PML-RARα fusion protein in NB4 cells following pretreatment with phenanthroline (i.e., chelator of zinc ions), indicating that the integrity of zinc finger motifs in PML-RARα fusion protein is a fundamental condition for inducing the protein's degradation by antimony and arsenic. Moreover, we found that SbIII could not induce mutant PML (e.g., A126V and L218P) solubility change and degradation, similar to As2O3. In contrast, we found that the organic antimony compound phenylstibine oxide (PSO) could induce mutant PML protein degradation. In conclusion, our results indicate that SbIII might also be a promising agent to treat acute promyelocytic leukemia, in the same manner as As2O3.

Aptamers are short, single-stranded nucleic acid (DNA or RNA) oligonucleotides that can be obtained by a technique called systematic evolution of ligands by exponential enrichment (SELEX) in vitro. Due to superior properties such as small size, high binding affinity, and stability, they are considered to be feasible tools for diagnosis and treatment of disease. In the current study, we attempted to screen a high-affinity DNA aptamer to selectively target the colorectal carcinoma Caco-2 cells by using cell-based SELEX approach. After 14 consecutive rounds of selection, aptamer ApC1 was identified. Confocal microscopy results revealed that ApC1 could rapidly internalize into Caco-2 cells but not HEK 293 cells. Moreover, it showed high specificity to Caco-2 cells rather than other cell lines such as 293T, HeLa, MCF-7, HL-60, and NB4. Collectively, our results demonstrated that aptamer ApC1 has high specificity to colorectal carcinoma Caco-2 cells, which could be further applied for targeted therapy of colorectal cancer in future studies.

In this paper, we present the procedure of estimating the aerodynamic coefficients for a commercial aviation aircraft from geometric parameters at low-cruise-flight conditions using US DATCOM (United States Data Compendium) and XFLR software. The purpose of this research was to compare the stability parameters from both pieces of software to determine the efficacy of software solution for a wide-body aircraft at the stated flight conditions. During the initial phase of this project, the geometric parameters were acquired from established literature. In the next phase, stability and control coefficients of the aircraft were estimated using both pieces of software in parallel. Results obtained from both pieces of software were compared for any differences and the both pieces of software were validated with analytical correlations as presented in literature. The plots of various parameters with variations of the angle of attack or control surface deflection have also been obtained and presented. The differences between the software solutions and the analytical results can be associated with approximations of techniques used in software (the vortex lattice method is the background theory used in both DATCOM and XFLR). Additionally, from the results, it can be concluded that XFLR is more reliable than DATCOM for longitudinal, directional, and lateral stability/control coefficients. Analyses of a Boeing 747-200 (a wide-body commercial airliner) in DATCOM and XFLR for complete stability/control analysis including all modes in the longitudinal and lateral directions have been presented. DATCOM already has a sample analysis of a previous version of the Boeing 737, however, the Boeing 747-200 is much larger than the former, and complete analysis was, therefore, felt necessary to study its aerodynamics characteristics. Furthermore, in this research, it was concluded that XFLR is more reliable for various categories of aircraft alike in terms of general stability and control coefficients, and hence many aircraft can be dependably modeled and analyzed in this software.

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation between chromosomes 15 and 17, t(15;17), resulting in the expression of PML-RARα fusion protein, which disrupts the normal PML nuclear bodies (PML-NBs) to micro-speckled pattern, leading to loss of their original functions. Moreover, reformation of PML-NBs in APL by arsenic is considered as one of the important step for APL treatment. Leptomycin B (LMB), a nuclear export inhibitor, is commonly used to inhibit the proteins exporting from the nucleus to the cytoplasm. In the present study, we found that LMB could induce the reformation of PML-NBs in leukemia NB4 cells as well as in APL blast cells from the patients, implying that nuclear shuttle proteins might be involved in the reformation of PML-NBs. Herein, we further found that LMB totally lost the ability to induce PML-NBs reformation when the endogenous PML gene was knocked out, indicating that endogenous PML protein is probably involved in the reformation of PML-NBs. More interestingly, among all PML isoforms (i.e., seven isoforms), reformation of PML-NBs was only observed when co-transfection of PML-RARα with PML-I after LMB treatment. Similarly, deletion of nuclear export signal (NES) of PML-I could also reform PML-NBs, suggesting that the protein level of endogenous PML-I in nucleus is important for the reformation of PML-NBs that interfered by PML-RARα fusion protein. Additionally, LMB has synergistic effect with iAsIII on enhancing PML-RARα fusion protein degradation, and it might provide new insight into APL treatment at clinical level in the near future.

Salvia moorcroftiana is an herbaceous plant commonly known as "Kallijari" in Pakistan and belongs to the family Lamiaceae. This study was carried out to evaluate its scientific base for its traditional use in pain, fever and inflammation. The powdered plant was extracted by the method of cold maceration using aqueous methanol (70:30) as solvents. Hot plate, flick tail and acetic acid induced writhing test were utilized for analgesic assessment. Anti-inflammatory activity was evaluated by carageenan-induced mice paw edema. Brewer's induced pyrexia was used for the evaluation of antipyretic activity. Non-significant (p0.01) results as compared to the standard were obtained in all experiments. It was evident from acute toxicity study that plant was non-toxic in nature. It is concluded from the study that plant had the potential to be safely used for pain, fever and inflammation.