Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3

BACKGROUND: We have earlier reported that follicle stimulating hormone (FSH) modulates ovarian stem cells which include pluripotent, very small embryonic-like stem cells (VSELs) and their immediate descendants ‘progenitors’ termed ovarian germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium (OSE). FSH may exert pleiotropic actions through its alternatively spliced receptor isoforms. Four isoforms of FSH receptors (FSHR) are reported in literature of which FSH-R1 and FSH-R3 have biological activity. Present study was undertaken to identify FSHR isoforms mediating FSH action on ovarian stem cells, using sheep OSE cells culture as the study model. METHODS: Cultures of sheep OSE cells (a mix of epithelial cells, VSELs, OGSCs and few contaminating red blood cells) were established with and without FSH 5IU/ml treatment. Effect of FSH treatment on self-renewal of VSELs and their differentiation into OGSCs was studied after 15 hrs by qRT-PCR using markers specific for VSELs (Oct-4A, Sox-2) and OGSCs (Oct-4). FSH receptors and its specific transcripts (R1 and R3) were studied after 3 and 15 hrs of FSH treatment by immunolocalization, in situ hybridization and qRT-PCR. FSHR and OCT-4 were also immuno-localized on sheep ovarian sections, in vitro matured follicles and early embryos. RESULTS: FSH treatment resulted in increased stem cells self-renewal and clonal expansion evident by the appearance of stem cell clusters. FSH receptors were expressed on ovarian stem cells whereas the epithelial cells were distinctly negative. An increase in R3 mRNA transcripts was noted after 3 hrs of FSH treatment and was reduced to basal levels by 15 hrs, whereas R1 transcript expression remained unaffected. Both FSHR and OCT-4 were immuno-localized in nuclei of stem cells, showed nuclear or ooplasmic localization in oocytes of primordial follicles and in cytoplasm of granulosa cells in growing follicles. CONCLUSIONS: FSH modulates ovarian stem cells via FSH-R3 to undergo potential self-renewal, clonal expansion as ‘cysts’ and differentiation into oocytes. OCT-4 and FSHR proteins (required initially to maintain pluripotent state of VSELs and for FSH action respectively) gradually shift from nuclei to cytoplasm of developing oocytes and are later possibly removed by surrounding granulosa cells as the oocyte prepares itself for fertilization

Comprimidos mucoadherentes bicapa para la administración bucal de carvedilol: Estudios in vitro e in vivo

Mucoadhesive bilayered system of carvedilol was designed for buccal application with the objective of improving bioavailabilityand producing sustained release. Carbopol 934P and hydroxypropylmethylcellulose K4M were employed ascarriers and the developed formulations were subjected for evaluation of surface pH, swelling index, in vitro bioadhesionand in vitro drug release studies. In vitro drug release data was analyzed for release kinetics by fi tting into Zeroorder, First order, Higuchi, Hixson-Crowell and Korsmeyer Peppas models. In vivo pharmacokinetic performance of theoptimized batch was investigated in rabbits. Data emerged from optimization and evaluation of the system revealed thatformulations exhibited satisfactory technological parameters and swelling indices. Formulation F5 showed maximumbioadhesion (3.5 ± 0.6 N) and was found to be retained for 7 h on porcine buccal mucosa. The model fi tting of invitro release data demonstrated that it followed zero order release pattern with non-fi ckian release behavior i.e. n valuesranging from 0.71 to 1.17, indicating the release was combination of tablet erosion and diffusion from the matrix.The obtained pharmacokinetic values showed signifi cant difference between Cmax, Tmax and area under curve values oforal and buccal formulation, i.e. increase in bioavailability of buccal tablet as compared with oral formulation. Plasmaconcentration curves for the buccal tablet clearly showed evidence of sustained release behavior.Se diseñó un sistema mucoadherente bicapa de carvedilol para administración bucal, con el objetivo de mejorar labiodisponibilidad y conseguir una liberación sostenida. Como portadores se utilizaron Carbopol 934P e hidroxipropilmetilcelulosaK4M, y las formulaciones obtenidas se sometieron a estudios de pH superfi cial, índice de expansióny bioadhesión y liberación de fármaco in vitro. Se analizó la cinética de los datos de liberación de fármaco in vitro,mediante ajuste en modelos de orden cero, primer orden, Higuchi, Hixson-Crowell y Korsmeyer Peppas. El estudiodel rendimiento farmacocinético in vivo del lote optimizado se realizó en conejos. Los datos obtenidos de la optimizacióny evaluación del sistema revelaron que las formulaciones presentaban índices de expansión y parámetrostecnológicos satisfactorios. La formulación F5 presentó el mayor grado de bioadherencia (3.5 ± 0.6 N) y su retenciónen la mucosa bucal porcina fue de 7 h. El ajuste al modelo de los datos de liberación in vitro demostró que seguíanun patrón de liberación de orden cero con un comportamiento de liberación no Fickian, es decir, con valores de nentre 0.71 y 1.17, lo que indica que la liberación fue una combinación de erosión del comprimido y difusión desdela matriz. Los valores farmacocinéticos obtenidos presentaron una diferencia signifi cativa entre Cmax, Tmax y losvalores del área bajo la curva de las formulaciones bucal y oral, es decir, un aumento de la biodisponibilidad enlos comprimidos bucales en comparación con la formulación oral. Las curvas de concentración en plasma de loscomprimidos bucales evidenciaron claramente un comportamiento de liberación sostenido

Mucoadhesive bilayer tablets for buccal delivery of carvedilol: in vitro and in vivo investigations.

Se diseñó un sistema mucoadherente bicapa de carvedilol para administración bucal, con el objetivo de mejorar la biodisponibilidad y conseguir una liberación sostenida. Como portadores se utilizaron Carbopol 934P e hidroxipropilmetilcelulosa K4M, y las formulaciones obtenidas se sometieron a estudios de pH superfi cial, índice de expansión y bioadhesión y liberación de fármaco in vitro. Se analizó la cinética de los datos de liberación de fármaco in vitro, mediante ajuste en modelos de orden cero, primer orden, Higuchi, Hixson-Crowell y Korsmeyer Peppas. El estudio del rendimiento farmacocinético in vivo del lote optimizado se realizó en conejos. Los datos obtenidos de la optimización y evaluación del sistema revelaron que las formulaciones presentaban índices de expansión y parámetros tecnológicos satisfactorios. La formulación F5 presentó el mayor grado de bioadherencia (3.5 ± 0.6 N) y su retención en la mucosa bucal porcina fue de 7 h. El ajuste al modelo de los datos de liberación in vitro demostró que seguían un patrón de liberación de orden cero con un comportamiento de liberación no Fickian, es decir, con valores de n entre 0.71 y 1.17, lo que indica que la liberación fue una combinación de erosión del comprimido y difusión desde la matriz. Los valores farmacocinéticos obtenidos presentaron una diferencia signifi cativa entre Cmax, Tmax y los valores del área bajo la curva de las formulaciones bucal y oral, es decir, un aumento de la biodisponibilidad en los comprimidos bucales en comparación con la formulación oral. Las curvas de concentración en plasma de los comprimidos bucales evidenciaron claramente un comportamiento de liberación sostenido.Mucoadhesive bilayered system of carvedilol was designed for buccal application with the objective of improving bioavailability and producing sustained release. Carbopol 934P and hydroxypropylmethylcellulose K4M were employed as carriers and the developed formulations were subjected for evaluation of surface pH, swelling index, in vitro bioadhesion and in vitro drug release studies. In vitro drug release data was analyzed for release kinetics by fi tting into Zero order, First order, Higuchi, Hixson-Crowell and Korsmeyer Peppas models. In vivo pharmacokinetic performance of the optimized batch was investigated in rabbits. Data emerged from optimization and evaluation of the system revealed that formulations exhibited satisfactory technological parameters and swelling indices. Formulation F5 showed maximum bioadhesion (3.5 ± 0.6 N) and was found to be retained for 7 h on porcine buccal mucosa. The model fi tting of in vitro release data demonstrated that it followed zero order release pattern with non-fi ckian release behavior i.e. n values ranging from 0.71 to 1.17, indicating the release was combination of tablet erosion and diffusion from the matrix. The obtained pharmacokinetic values showed signifi cant difference between Cmax, Tmax and area under curve values of oral and buccal formulation, i.e. increase in bioavailability of buccal tablet as compared with oral formulation. Plasma concentration curves for the buccal tablet clearly showed evidence of sustained release behavio

Biosynthesis of silver nanoparticles by Pseudomonas spp. isolated from effluent of an electroplating industry

The aim of this study was to isolate and screen bacteria from soil and effluent of electroplating industries for the synthesis of silver nanoparticles and characterize the potential isolate. Soil and effluent of electroplating industries from Mumbai were screened for bacteria capable of synthesizing silver nanoparticles. From two soils and eight effluent samples 20 bacterial isolates were obtained, of these, one was found to synthesize silver nanoparticles. Synthesis of silver nanoparticle by bacteria was confirmed by undertaking characterization studies of nanoparticles that involved spectroscopy and electron microscopic techniques. The potential bacteria was found to be Gram-negative short rods with its biochemical test indicating Pseudomonas spp. Molecular characterization of the isolate by 16S r DNA sequencing was carried out which confirmed its relation to Pseudomonas hibiscicola ATCC 19867. Stable nanoparticles synthesized were 50 nm in size and variable shapes as seen in SEM micrographs. The XRD and FTIR confirmed the crystalline structure of nanoparticles and presence of biomolecules mainly proteins as agents for reduction and capping of nanoparticles. The study demonstrates synthesis of nanoparticles by bacteria from effluent of electroplating industry. This can be used for large scale synthesis of nanoparticles by cost effective and environmentally benign mode of synthesis

Retraction Note: Follicle stimulating hormone modulates ovarian stem cells through alternately spliced receptor variant FSH-R3

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1757-2215-6-52

A Novel Approach for Multichannel Epileptic Seizure Classification Based on Internet of Things Framework Using Critical Spectral Verge Feature Derived from Flower Pollination Algorithm

A novel approach for multichannel epilepsy seizure classification which will help to automatically locate seizure activity present in the focal brain region was proposed. This paper suggested an Internet of Things (IoT) framework based on a smart phone by utilizing a novel feature termed multiresolution critical spectral verge (MCSV), based on frequency-derived information for epileptic seizure classification which was optimized using a flower pollination algorithm (FPA). A wireless sensor technology (WSN) was utilized to record the electroencephalography (EEG) signal of epileptic patients. Next, the EEG signal was pre-processed utilizing a multiresolution-based adaptive filtering (MRAF) method. Then, the maximal frequency point at which the power spectral density (PSD) of each EEG segment was greater than the average spectral power of the corresponding frequency band was computed. This point was further optimized to extract a point termed as critical spectral verge (CSV) to extract the exact high frequency oscillations representing the actual seizure activity present in the EEG signal. Next, a support vector machine (SVM) classifier was used for channel-wise classification of the seizure and non-seizure regions using CSV as a feature. This process of classification using the CSV feature extracted from the MRAF output is referred to as the MCSV approach. As a final step, cloud-based services were employed to analyze the EEG information from the subject’s smart phone. An exhaustive analysis was undertaken to assess the performance of the MCSV approach for two datasets. The presented approach showed an improved performance with a 93.83% average sensitivity, a 97.94% average specificity, a 97.38% average accuracy with the SVM classifier, and a 95.89% average detection rate as compared with other state-of-the-art studies such as deep learning. The methods presented in the literature were unable to precisely localize the origination of the seizure activity in the brain region and reported a low seizure detection rate. This work introduced an optimized CSV feature which was effectively used for multichannel seizure classification and localization of seizure origination. The proposed MCSV approach will help diagnose epileptic behavior from multichannel EEG signals which will be extremely useful for neuro-experts to analyze seizure details from different regions of the brain

Synthesis of zinc oxide nanoparticles using plant leaf extract against urinary tract infection pathogen

In modern science, Nanotechnology is an ablaze field for the researchers. Zinc oxide nanoparticles (ZnO NPs) are known to be one of the most multifunctional inorganic nanoparticles with its application in treatment of urinary tract infection. Nanoparticles were synthesized using Passiflora caeruleafresh leaf extract and were characterized by UV-visible spectroscopy (UVâvis), X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), Energy dispersive analysis of x-ray (EDAX), Atomic force microscopy (AFM). Therefore, the study reveals an efficient, eco-friendly and simple method for the green synthesis of multifunctional ZnO NPs using P. caerulea. Urinary tract infection causing microbes were isolated from the disease affected patient urine sample. The synthesized nanoparticles have been tested against the pathogenic culture showed a very good zone of inhibition compared with plant extract. It indicates the biomedical capability of ZnO NPs. Keywords: Green synthesis, Zinc oxide nanoparticles, Antimicrobial activity, Urinary tract infection pathogen