Microwave-assisted synthesis, characterizations, antimicrobial activities, and DFT studies on some pyridine derived Schiff base

This study reports a joint experimental, theoretical and microbiological investigation on the (E)-N,N-dimethyl-4-((pyridine-2-ylmethylene)amino)aniline (5), (E)-N,N-dimethyl-4-((pyridine-4-ylmethylene)amino)aniline (6) and (E)-N,N-dimethyl-4-((pyridine-3-ylmethylene)amino)aniline (7). These compounds were synthesized with microwave method and their structures characterized by FT-IR, 1H-NMR, 13C-NMR, and elemental analysis tecniques. In the theoretical studies, torsional barriers analysis, ground state structure, Fourier Transform Infrared spectra (FT-IR), and Nuclear Magnetic Resonance spectra (NMR) of 5, 6, and, 7 were calculated by Density Functional Theory (DFT) computations. The conformers obtained from the torsional barrier scanning were optimized by B3LYP/6-31G(d,p) level. The harmonic vibrational frequencies, potential energy distribution (PED), infrared intensities, and NMR chemical shifts of the most stable conformers were determined using the B3LYP/6-311++G(d,p). Theoretically, predicted spectral data were compared with experimental results. Antimicrobial studies of the synthesized compounds were performed against various microbial strains. Antimicrobial activities of 5, 6, and, 7 were tested against selected bacteria and yeast through minimum inhibitory concentration (MIC) and diffusion method. Compound 7 was found to be the most active against bacteria and yeast, while compound 5 was found to be moderately active. Compounds 6 (against S. aureus and C. albicans) and, 7 were found to have a very high minimum inhibitory concentration, ranging between 1.95 and 7.81 g/mL (against P. aeruginosa and E. coli). Compounds (6 and 7) showed zone of inhibition values in the range of 10–20 mm against other bacteria except L. monocytogenes and S. thyphimurium. © 2022 Elsevier B.V

Cutaneous leishmaniasis in Karak, Pakistan: Report of an outbreak and comparison of diagnostic techniques

A total of 339 patients with clinically suspected cutaneous leishmaniasis (CL) were studied from March to April, 2010 in three villages of Karak, Khyber Pakhtunkhwa, Pakistan where an epidemic of the disease was in question. Using polymerase chain reaction (PCR), 78.17% (265/339) were observed having CL. Microscopically, however, only 43.06% (146/339) were diagnosed with the disease. This study reports and confirms epidemic of CL in both gender of all ages in the area. Females (70.94%) were noted to be predominantly affected as compared to males (29%). Clinically, 12.38% of patients had more than three lesions, 29.20% had two lesions, while 58.40% had only single lesion. Most lesions were found on exposed surfaces of the body (predominantly hands, face and feet). The present study confirms that PCR was more sensitive than microscopic examination.Key words: Epidemic, cutaneous leishmaniasis, polymerase chain reaction (PCR), microscopy, Pakistan

Prevalence and detection of cytomegalovirus by polymerase chain reaction (PCR) and simple ELISA in pregnant women

A total of 327 women were screened, amongst them, 7 (2.14%) were cytomegalovirus (CMV) DNA positive by polymerase chain reaction (PCR). Antibodies against toxoplasma were also detected in 106 (32.41%) women, while 54 (16.51%) were anti CMV positive. Eleven (3.36%) and thirteen (3.97%) women were anti HSV and anti Rubella virus positive, respectively. High prevalence was recorded in age group 21 to 30 years which was 2.53% (4/158), followed by the age group <20 years which was 2.27% (1/44), then in age group 31 to 40 years, 2.25% (2/89) CMV DNA were detected by PCR and 0% was recorded in age group of above 40 years. The overall prevalence of human cytomegalovirus (HCMV) infection in 16 to 45 year-old was 2.14% by PCR and the number of abortion noted was 0 to 5 times. Active infection of HCMV was observed in women with number of abortion. Force of infection was significantly higher among age group 21 to 30 and 31 to 40 years. PCR was a more sensitive, reliable and accurate method for the detection of HCMV infection in pregnant women during this study.Key words: Cytomegalovirus, PCR, human cytomegalovirus (HCMV) and ELIS

Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells

Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs’ intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS

MEFV mutations in systemic JIA

Background: Systemic form of juvenile idiopathic arthritis (JIA) is regarded as an autoinflammatory disease. Certain genetic polymorphisms in genes coding inflammatory proteins have been associated with the disease. On the other hand mutations of the MEFV gene cause a monogenic autoinflammatory disease, Familial Mediterranean Fever (FMF). In a previous study in adult rheumatoid arthritis 3 out of the 25 British patients who developed secondary amyloidosis had a mutation/polymorphism in the MEFV gene. Aim: To analyse whether mutaions in the MEFV gene had an association with systemic JIA. Patients and methods: MEFV mutations were screened in a total of 32 systemic JIA patients. All had been classified as systemic JIA according to the Durban JIA criteria. None had disease characteristics that met the Tel Hashomer criteria for the diagnosis of FMF. Results: 2 carrier for M694V and two patients who were homozygote for MEFV mutations. Both of these patients were among the most severe patients in the group. One had an excellent response to etanercept whereas the other was resistant to anti-TNF and other conventional treatments and had only a partial response to thalidomide. Although the number of severe mutations were increased in this small group of patients with systemic JIA the difference with the Turkish population did not reach statistical significance, but the disease causing mutation (M694V) was significantly high in the patients with systemic JIA(p = 0.02). Conclusion: However, the severe disease course in the aforementioned patients suggest that MEFV mutations may be a modifying genetic factor in systemic JIA.PubMe

Evolución de los ácidos grasos en el mesocarpo del níspero (Mespilus germanica. L.) a diferentes estados de maduración

The fatty acid composition of medlar (Mespilus germanica L.) varied significantly among the ripening stages sampled at 157, 172 and 187 DAFs (days after full bloom). Twenty-one different fatty acids were detected in preclimacteric fruit and 17 when the climacteric began. Principal fatty acids, determined in medlar fruit harvested from October (157 and 172 DAFs) to November (187 DAF) were mainly palmitic acid (16:0), linoleic acid (18:2n-6), and a-linolenic acid (18:3n-3). While the content of saturated fatty acids [palmitic acid (16:0) and stearic acid (18:0)] increased, the content of the essential polyunsaturated fatty acids [linoleic acid (18:2n-6) and linolenic acid (18:3n-3)] decreased through ripening, in parallel with pulp darkening. The percentage of linoleic acid and a-linolenic acid in ripe, hard fruits was 60.0 and 13.5 % of dry wt at 157 DAF which decreased throughout ripening, remaining at 28.7 and 5.6 % of dry wt, respectively, in the fully softened and darkened pulp. A marked decreases in the double bond index, percentage of unsaturation and the ratio of unsaturation/saturation were also seen throughout the medlar ripening. The contribution of unsaturated fatty acid to the total fatty acid content decreased markedly as the medlar fruit became progressively softer and darkened.La composición en ácidos grasos del níspero (Mespilus germanica L.) varió significativamente entre los estados de maduración muestreados a los 157, 172 y 187 DAFs (días después de la floración). Veinte y un ácidos grasos diferentes fueron detectados en el fruto preclimatérico y 17 cuando comenzó el climaterio. Los ácidos grasos principales encontrados en nísperos, recolectados desde Octubre (157 y 172 DAFs) hasta Noviembre (187 DAF), fueron principalmente ácido palmítico (16:0), ácido linoléico (18:2n-6), y ácido a-linolénico (18:3n-3). En tanto que el contenido en ácidos grasos saturados (ácido palmítico (16:0) y ácido esteárico (18:0)) aumentó, el contenido en ácidos grasos esenciales (ácido linoleico (18:2n-6) y ácido linolénico (18:3n-6)) disminuyó durante la maduración, en paralelo con el oscurecimiento de la pulpa. El porcentaje de ácido linoleico y de ácido a-linolénico en frutos maduros sin reblandecer fue de 60.0 y 13.5 % del peso seco a 157 DAF, disminuyendo durante la maduración, y permaneciendo a 28.7 y 56 % del peso seco, respectivamente, en la pulpa completamente blanda y oscura. También se observó durante la maduración del níspero una marcada disminución en el número de dobles enlaces, en el tanto por ciento de instauración y en la relación instauración / saturación. La contribución de los ácidos grasos insaturados al contenido de ácidos grasos totales disminuyó marcadamente cuando el níspero comenzó progresivamente a reblandecerse y oscurecerse

Ultracompact microinterferometer-based fiber Bragg grating interrogator on a silicon chip

We report an interferometer-based multiplexed fiber Bragg grating (FBG) interrogator using silicon photonic technology. The photonic-integrated system includes the grating coupler, active and passive interferometers, interferometers, a 12-channel wavelength-division-multiplexing (WDM) filter, and Ge photodiodes, all integrated on a 6x8 mm2 silicon chip. The system also includes optical and electric interfaces to a printed board, which is connected to a real-time electronic board that actively performs the phase demodulation processing using a multitone mixing (MTM) technique. The device with active demodulation, which uses thermally-based phase shifters, features a noise figure of σ  =  0.13 pm at a bandwidth of 700 Hz, which corresponds to a dynamic spectral resolution of 4.9 fm/Hz1/2. On the other hand, the passive version of the system, based on a 90º-hybrid coupler, features a noise figure of σ  =  2.55 pm at a bandwidth of 10 kHz, also showing successful detection of a 42 kHz signal when setting the bandwidth to 50 kHz. These results demonstrate the advantage of integrated photonics, which allows the integration of several systems with different demodulation schemes in the same chip and guarantees easy scalability to a higher number of ports without increasing the dimensions or the cost

The Glial Regenerative Response to Central Nervous System Injury Is Enabled by Pros-Notch and Pros-NFκB Feedback

Organisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying structural robustness and plasticity are poorly understood, but can be investigated by probing how cells respond to injury. Injury to the CNS induces proliferation of enwrapping glia, leading to axonal re-enwrapment and partial functional recovery. This glial regenerative response is found across species, and may reflect a common underlying genetic mechanism. Here, we show that injury to the Drosophila larval CNS induces glial proliferation, and we uncover a gene network controlling this response. It consists of the mutual maintenance between the cell cycle inhibitor Prospero (Pros) and the cell cycle activators Notch and NFκB. Together they maintain glia in the brink of dividing, they enable glial proliferation following injury, and subsequently they exert negative feedback on cell division restoring cell cycle arrest. Pros also promotes glial differentiation, resolving vacuolization, enabling debris clearance and axonal enwrapment. Disruption of this gene network prevents repair and induces tumourigenesis. Using wound area measurements across genotypes and time-lapse recordings we show that when glial proliferation and glial differentiation are abolished, both the size of the glial wound and neuropile vacuolization increase. When glial proliferation and differentiation are enabled, glial wound size decreases and injury-induced apoptosis and vacuolization are prevented. The uncovered gene network promotes regeneration of the glial lesion and neuropile repair. In the unharmed animal, it is most likely a homeostatic mechanism for structural robustness. This gene network may be of relevance to mammalian glia to promote repair upon CNS injury or disease