A metabolomics approach for the evaluation of Ficus benghalensis female in vivo reproductive effects relative to its metabolite fingerprint as determined via UPLC-MS and GC-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus benghalensis, commonly known as Banyan Fig, is the national tree of India and its aerial roots are used traditionally to treat female reproductive disorders. However, despite this traditional use, no pharmacological evidence could be traced supporting this use. Additionally, no comprehensive metabolite profiling was reported for F. benghalensis aerial roots. AIM OF THE STUDY: This study attempts to justify biochemically the traditional use of F. benghalensis aerial roots in treatment of female reproductive disorders and in relation to its secondary metabolite profile. MATERIALS AND METHODS: Total ethanol extract (TEE) and subfractions [petroleum ether (PEF), chloroform (CHF), ethyl acetate (EAF) and n-butanol (BUF] were prepared from air-dried powdered aerial roots of F. benghalensis. Detailed in-vivo investigation of the hormonal activity and action mechanism of the total ethanol extract and subfractions was carried out through evaluation of estrogenic and gonadotropic activities. The estrogenic activity was evaluated on ovariectomized immature female rats through estimating uterine weight, vaginal cornification and serum estradiol level along with histological examination of uteri. The gonadotropic activity was measured by assay of follicle stimulating hormone (FSH) and luteinizing hormone (LH) like activities. Total follicular and corpora lutea counts in immature female rats were used to determine FSH and LH like activities, respectively in addition to histological picture of the genitalia. Comprehensive non-targeted metabolite profiling was carried out for the TEE and subfractions using UPLC-HRMS in negative and positive ionization modes. UPLC-MS fingerprint was subjected to principal component analysis (PCA) and partial least squares analyses to correlate the bioactivities to specific chemical constituents in F. benghalensis different subfractions. GC-MS was further used for non-polar silylated fractions. RESULTS: Results revealed that only the non-polar PEF and CHF displayed moderate estrogenic and FSH-like activities but with no LH-like activity. Metabolites profiling via (UPLC-HRMS) and multivariate PCA analysis enabled identification and comparison of various chemical classes in F. benghalensis extract and fractions. The active non-polar fractions revealed nearly similar metabolites profile being composed of isoflavonoids, triterpenes, sterols, fatty acids and cyclic peptides. In contrast, polar fractions were more abundant in apocarotenoids, fatty acyl amides, hydroxybenzoates and hydroxycinnamates in addition to two lignans. PLS analysis revealed strong correlation between hydroxylated fatty acids and pyranoisoflavones with estrogenic and FSH-like activities. GC-MS analysis was further employed for non-polar fractions profiling revealing for their enrichment in fatty acids/esters, terpenes, organic acids and phenolics. CONCLUSION: This is the first study to rationalize the use of F. benghalensis aerial root traditionally in treatment of gynecological disorders, revealing that the petroleum ether and chloroform non-polar subfractions of F. benghalensis showed estrogenic and FSH-like activity with absence of LH-like activity. This biological activity could possibly be attributed to its metabolites profile of isoflavonoids, fatty acids, triterpenes, sterols and cyclic peptides identified via UPLC-MS and GC-MS techniques. Consequently, F. benghalensis aerial roots should be used with caution in traditional treatment of female infertility or other reproductive disorders.

Assessment of Ferula hermonis Boiss fertility effects in immature female rats supported by quantification of ferutinin via HPLC and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula hermonis is a small shrub renowned for its aphrodisiac abilities. Middle East herbalists have utilized Ferula hermonis seed and root as an aphrodisiac folk medicine to treat women's frigidity and male erectile and sexual dysfunction. AIM OF THE STUDY: Assessment of follicle-stimulating hormone-like (FSH), luteinizing hormone-like (LH), and estrogenic activities of the methanolic extract (ME) of the roots of Ferula hermonis on female reproductive function. MATERIALS AND METHODS: The methanolic extract was prepared from the root of F. hermonis and studied at dose level 6 mg/kg in immature female rats for FSH-like, LH-like, and estrogenic activities. These activities were determined by analyzing gross anatomical features, relative organ weight, and serum level of FSH, LH, progesterone and estrogen hormones, and histopathological characteristics. Quantification of the main phytoestrogenic component ferutinin carried out by HPLC. In addition, molecular docking for the binding affinity of ferutinin inside active sites of both estrogen receptor alpha (ERα) and FSH receptor (FSHR) was performed to predict the potential role of ferutinin in regulating the female reproductive process. RESULTS: Ferula hermonis (ME) showed potent FSH-like, LH-like activities and moderate estrogenic effect at the dose of 6 mg/kg. The content of ferutinin in F. hermonis was estimated to be 92 ± 1.33 mg/g of the methanolic extract. Molecular docking of ferutinin with ERα and FSHR displayed strong interaction with target proteins. CONCLUSIONS: Based on results, it can be concluded that Ferula hermonis can be considered as a suitable female fertility improving agent.

Respiratory Distress and Chest Pain in an Airplane Passenger With Radiolucent Left Hemithorax.

CASE PRESENTATION: A 43-year-old man experienced sudden onset of chest pain and shortness of breath onboard a domestic flight. After consultation with the airline's operations center, a decision was made to land the plane in its destination airport. After landing, an ambulance was ready, and the patient was transferred to the ED in our facility. Patient evaluation was immediately started, and oxygen supply and venous access were secured.

Characterization of Nuclear Progesterone Receptor Isoforms in the Term Equine Placenta.

In equine parturition, the role of progestins along with the nuclear progesterone receptor (nPR) signaling pathway in the placenta is not completely clarified. The progestins play an integral role in maintaining myometrial quiescence during the late stage of pregnancy via acting on nPR isoforms (PRA and PRB; PRB is more active than PRA). The current study aimed to determine the PRA and PRB expressions in the term equine placenta at the gene and protein levels. Six term equine placentas were used in this study. Reverse transcription polymerase chain reaction (RT-PCR) was used to quantify the mRNA expression for PRA and PRB. The protein expression was detected using the Western Blot technique. The results revealed that the mRNA and protein expressions for PRA were significantly higher (P < 0.0001) in the term equine placental tissue compared to the mRNA and protein expressions of PRB. These results demonstrated that nPRs are detectable in the term placenta of mares and PRA is the dominant isoform expressed. The present findings raised the possibility that the PRA plays an important role in the parturition process and expulsion of the placenta in mares.

Unilateral Giant Bullae: Pulmonary Placental Transmogrification Should Be Kept in Mind: Case Reports.

Placental transmogrification is a peculiar clinical entity of the lung of uncertain etiology. We report 2 cases of pulmonary placental transmogrification in 2 patients of different nationalities. Both of them had no history of smoking or chronic lung disease. The main presentations were dyspnea and chest pain. Radiologic studies showed a unilateral giant bulla in both patients; additional pneumothorax was present in only 1patient. They underwent surgical bullectomy. Histopathologic studies revealed the presence of intracystic placenta-like villous structures and a diagnosis of placental transmogrification was made. Placental transmogrification should be considered in cases of unilateral bullae.

In vitro acaricidal activity of green synthesized nickel oxide nanoparticles against the camel tick, Hyalomma dromedarii (Ixodidae), and its toxicity on Swiss albino mice.

The green synthesized nanoparticles have been determined as a novel pesticide against arthropod pests. This study was designed to evaluate the in vitro acaricidal activity of green synthesized nickel oxide nanoparticles (NiO NPs) using aqueous extract of Melia azedarach ripened fruits against different developmental stages of the camel tick Hyalomma dromedarii in addition to their toxic effect on laboratory animals. The synthesized NiO NPs were characterized by UV-visible (UV-Vis) spectroscopy, Fourier transforms infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). The UV-Vis spectra of the NiO NPs showed an absorption peak at 307 nm. FTIR analysis showed the possible functional groups used for capping and stabilization of NiO NPs with strong bands at 3416.2 and 1626.6 cm-1. The SEM images of the NiO NPs exhibited a size ranging from 21 to 35 nm. The immersion test was used for the in vitro application of the synthesized NiO NPs on the various tick stages (egg, nymph, larva, and adult). Mortality percentages and LC50 values of each tick stage were calculated. The oviposition and hatchability of the engorged females were monitored for the survived tick after treatment. The LC50 values for NiO NPs on embryonated eggs, larvae, and engorged nymphs were 5.00, 7.15, and 1.90 mg/mL, respectively. The egg productive index (EPI), egg number, and hatchability (%) were lower in females treated with the NiO NPs than in control ticks. The toxicity of the NiO NPs on laboratory animals was also investigated using Swiss albino mice by oral dose of 500 mg/kg/day administration for five consecutive days. The hematological, biochemical, and histopathological changes were evaluated. The hematological analysis showed significant increase in the level of white blood cells (WBC) and hemoglobin (Hb). Biochemical analysis showed non-significant decrease in alkaline phosphatase (ALP) and alanine amino transferase (ALT). We concluded that NiO NPs have a significant acaricidal activity as demonstrated on eggs, larvae, engorged nymphs, and fully fed females of H. dromedarii. From a toxicological point of view further in vivo investigations are needed to determine the mechanism of toxic effect of NiO NPs.

Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-b]Thiazole Linked Thiadiazole Conjugates.

BACKGROUND: Imidazo[2,1-b]thiazole scaffolds were reported to possess various pharmaceutical activities. RESULTS: The novel compound named methyl-2-(1-(3-methyl-6-(p-tolyl)imidazo[2,1-b]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1-b]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a-j and 7-9 had produced the respective 1,3,4-thiadiazole derivatives 6a-j and 10-12. The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, 1H-NMR and 13C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG2). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer. CONCLUSION: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.

A biochemometric approach for the assessment of Phyllanthus emblica female fertility effects as determined via UPLC-ESI-qTOF-MS and GC-MS.

Phyllanthus emblica L. fruits have long been used in Ayurvedic medicine for their many health benefits. In this study, we present P. emblica fruit crude extract and fractions' effects on the female reproductive system by assessing its estrogenic and gonadotropic activities. Results revealed that the non-polar petroleum ether and chloroform fractions exhibited the strongest estrogenic and follicle-stimulating hormone-like [FSH] activity, while the n-butanol fraction exhibited a significant luteinizing hormone-like [LH] activity. The ethyl acetate fraction showed neither estrogenic nor gonadotropic activities and in contrast it may impair female fertility suggesting that different metabolite classes contribute to the plant's overall effect on female fertility. To pinpoint active agents in these fractions, UPLC/ESI-qTOF-MS- was employed for secondary metabolite profiling with 100 metabolites annotated including ellagitannins, gallic acid derivatives, terpeneoids, sterols, phthalates and fatty acids. Correlation between extracts/fraction bioassays and UPLC/MS data was attempted using orthogonal partial least squares-discriminant analysis (OPLS-DA) revealing that guaiane-type sesquiterpenes, phthalates, diterpenes and oxygenated fatty acids showed positive correlation with estrogenic and gonadotropic activities. In contrast, mucic acid gallates, gallic acid derivatives and ellagitannins correlated negatively. GC/MS analysis of the non-polar bioactive fractions viz. petroleum ether and chloroform was also attempted which revealed its enrichment in fatty acids/fatty acyl esters (34%) and phenolic compounds (19.6%). This study provides the first report on the estrogenic and gonadotropic activities of P. emblica fruits in relation to their metabolite fingerprint.

The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon.

Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s.c.) twice weekly for 4 weeks in a single-arm, phase 1b/2a study. Within sigmoid mucosa, global transcriptomic analyses revealed 248 modulated genes (false discovery rate<0.05) including many type I interferon (IFN)-stimulated genes. MGN1703 increased the frequencies of cells exhibiting MX1 (P=0.001) and ISG15 (P=0.014) protein expression. No changes were observed in neutrophil infiltration (myeloperoxidase; P=0.97). No systematic effect on fecal microbiota structure was observed (analysis of similarity Global R=-0.105; P=0.929). TLR9 expression at baseline was inversely proportional to the change in integrated HIV DNA during MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.

Antiviral gene expression in psoriasis.

BACKGROUND: Psoriasis patients have relatively infrequent cutaneous viral infections compared to atopic dermatitis patients. Increased expression of four antiviral proteins (MX1, BST2, ISG15 and OAS2) has been reported in psoriatic skin and genetic studies of psoriasis have identified susceptibility genes in antiviral pathways. OBJECTIVE: To determine if psoriasis is associated with pervasive expression of antiviral genes in skin and blood. METHODS: We performed RNA sequencing on skin samples of 18 subjects with chronic plaque psoriasis and 16 healthy controls. We examined the expression of a predefined set of 42 antiviral genes, each of which has been shown in previous studies to inhibit viral replication. In parallel, we examined antiviral gene expression in atopic dermatitis, non-lesional psoriatic skin and psoriatic blood. We performed HIV-1 infectivity assays in CD4+ peripheral blood T cells from psoriatic and healthy individuals. RESULTS: We observed significant overexpression of 16 antiviral genes in lesional psoriatic skin, with a greater than two-fold increase in ISG15, RSAD2, IRF7, MX2 and TRIM22 (P < 1E-07). None of these genes was overexpressed in atopic dermatitis skin (P < 0.0001) or non-lesional psoriatic skin. In contrast to the skin compartment, no differences in antiviral gene expression were detected in the peripheral blood of psoriasis cases compared to healthy controls. CD4+ T cells from both psoriatic and healthy patients supported HIV-1 infection at a similar rate. CONCLUSION: Our findings highlight psoriasis as an inflammatory disease with cutaneous but not systemic immune activation against viral pathogens.

Headscarf pin, a sharp foreign body aspiration with particular clinical characteristics.

The process of wearing head scarf is very complex; girls used to hold a number of pins in the mouth and utilize them one by one to fix the scarf. Loss of concentration results in pin aspiration. We presented our experience with scarf pin aspiration and discussed the unique clinical characteristics of this problem. We reviewed the records of 73 patients who underwent bronchoscopy for scarf pin inhalation during the period from January 1995 to May 2009. The following data were collected, history of aspiration, time lag before presentation, symptoms and signs, radiological findings, bronchoscopic findings, number of repeated bronchoscopy, complications, need for thoracotomy and time of discharge. All patients were female, mean age 13.4 years. The time lag before admission was <12 h for 59 (81%) patients. Positive history was present in all cases. Chest radiography identified the pins in all cases. The foreign bodies were seen in the left bronchial system in 37 (50.7%) patients, in the right bronchial system in another 24 (32.9%), and in the trachea in 12 (16.4%) patients. In 66 (90.4%) patients, the foreign body was removed in the first bronchoscopic trial; a second trial was needed in 5 (6.8%) patients, and thoracotomy was performed in two patients. In conclusion, head scarf pin aspiration occurs in adolescent Islamic girls. The clinical presentation and radiological findings are diagnostic in all cases. Rigid bronchoscopy is the preferred treatment modality. Health education is the key issue in the prevention of this problem.

Is Routine Spiral CT-Chest Justified in Evaluation of the Major Blunt Trauma Patients?

STUDY: New generation spiral CT scanners permit multiple consecutive CT examinations on the same trauma patient in a short period of time. The purpose of this study was to evaluate the diagnostic role and therapeutic impact of routine spiral CT chest in multiply injured patients or patients with a suspicious mechanism of injury. PATIENTS AND METHODS: This prospective study included 443 patients with blunt chest trauma. All patients underwent a spiral CT chest as part of their routine evaluation. Radiological interpretation of chest x-rays, CT scan findings, and changes in management plan guided by these findings were recorded. RESULTS: The mechanism of injury was road traffic accidents in 422 patients (95.26%). Out of the 167 patients with normal chest radiograph, 136 (81.43%) were found to have an abnormality on chest CT. The management was changed in the form of additional investigations or unplanned intervention in 92 patients (20.76%). Additional investigations included transoesophageal echocardiography (n = 7), bronchoscopy (n = 13), transfer to higher center for aortography (n = 2). Intercostal tubes (n = 55), thoracotomies (n = 4), fixation of sternal fracture (n = 9), laparotomy (n = 1) and spinalfixation (n = 1) were performed following the CT scan. CONCLUSION: Although the incidence of significant injuries identified by the chest CT scan was low, it did prompt immediate intervention in a significant number of patients; some of them had potentially life-threatening injuries. Routine use of CT scanning is warranted in early evaluation of polytrauma patients or patients with severe blunt chest trauma.

Biomonitoring of n-nitroso compounds, nitrite and nitrate in the urine of Egyptian bladder cancer patients with or without Schistosoma haematobium infection.

The excretion of nitrate, nitrite, apparent total N-nitroso compounds and volatile nitrosamines was measured in 24 hr urine from 61 Egyptians, divided into 4 groups: controls, Schistosoma haematobium-infected patients and bladder cancer patients with and without a history of schistosomal infection. Urinary nitrate in S. haematobium-infected patients was significantly higher than in the other 3 groups. Nitrite was below the detection limit of the method (