N-Methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA

BACKGROUND: Cellular senescence is a state in which mammalian cells enter into an irreversible growth arrest and altered biological functions. The senescence response in mammalian cells can be elicited by DNA-damaging agents. In the present study we report that the DNA-damaging agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is able to induce senescence in the HCT-116 colon cancer cell line. RESULTS: Cells treated with lower concentrations of MNNG (0–25 microM) for 50 h showed a dose-dependent increase in G(2)/M phase arrest and apoptosis; however, cells treated with higher concentrations of MNNG (50–100 microM) showed a senescence-like G(0)/G(1 )phase arrest which was confirmed by increased expression of β-galactosidase, a senescence induced marker. The G(2/)M phase arrest and apoptosis were found to be associated with increased levels of p53 protein, but the senescence-like G(0)/G(1 )phase arrest was dissociated with p53 protein levels, since the p53 protein levels decreased in senescence-like arrested cells. We further, determined whether the decreased level of p53 was a transcriptional or a translational phenomenon. The results revealed that the decreased level of p53 protein in senescence-like arrested cells was a transcriptional phenomenon since p53 mRNA levels simultaneously decreased after treatment with higher concentrations of MNNG. We also examined the effect of MNNG treatment on other cell cycle-related proteins such as p21, p27, cyclin B1, Cdc2, c-Myc and max. The expression levels of these proteins were increased in cells treated with lower concentrations of MNNG, which supported the G(2)/M phase arrest. However, cells treated with higher concentrations of MNNG showed decreased levels of these proteins, and hence, may not play a role in cell cycle arrest. We then examined a possible association of the expression of APC protein and telomeric DNA signals with cellular senescence in MNNG-treated cells. We found that protein and mRNA levels of APC were drastically reduced in cells treated with higher concentrations of MNNG. The loss of APC expression might lead to chromosomal instability as well as microtubular disorganization through its dissociation with tubulin. In fact, the protein level of α-tubulin was also drastically decreased in senescence-like arrested cells treated with higher concentrations of MNNG. The levels of telomeric DNA also decreased in cells treated with higher concentrations of MNNG. CONCLUSIONS: These results suggest that in response to DNA alkylation damage the senescence-like arrest of HCT-116 cells was associated with decreased levels of APC protein, microtubular organization, and telomeric DNA

Cefuroxime axetil induced glossitis: a case report

Cefuroxime axetil is a semi synthetic cephalosporin antibiotic, which is prescribed for different types of infections such as lung, ear, throat, urinary tract, and skin. This is the drug of choice in the treatment and prevention of streptococcal infections. In this case, the patient was prescribed cefuroxime axetil, diclofenac, and paracetamol for pharyngitis. The patient developed glossitis 3 hrs after ingestion of above drugs which improved after withdrawing the offending drug. Glossitis is an uncommon, but serious adverse drug effect of cefuroxime axetil. It is important to recognize and manage it to prevent fatality. The case has been reported to the Pharmacovigilance Center Uttar Pradesh Rural Institute of Medical Sciences and Research Saifai, Etawah

Assessment of drug prescribing pattern using WHO indicators in hospitalized patients at a tertiary care teaching hospital in rural area of India

Background: To promote rational drug use in patients of rural areas, it is important to assess drug use pattern using the WHO prescription indicators. The aim of this study was to assess the drug prescription patterns in patients admitted in Medicine department of UPRIMS&R.Methods: A prospective observational study was conducted from Jan 2015 to June 2015. Data were collected & analysed according to WHO prescribing indicators and presented by using descriptive statistics.Results: 626 prescriptions were selected in which 3205 drugs were prescribed. The most common drug groups prescribed were antibiotics 24.64% followed by anti-diabetic drugs 12.38%, analgesics 12.23% and drugs for cardiovascular diseases 11.82%, GIT drugs 9.01%. Average number of drugs per prescription was 5.11. Drugs prescribed from essential drugs list (India) was 76.06%. Drugs prescribed from essential drugs list (WHO) was 23.04%. Total number of prescriptions with antibiotics was 24.27%. Total number of prescriptions with injections was 24.05%. Percentage of fixed dose combinations was 28.7%. Drugs prescribed by generic name were 89.88%.Conclusions: The prescribing pattern of antibiotics was according to WHO recommendations while the average number of drugs per prescription was found high. There were small differences in the values of drugs prescribed by generic names, injectable and drugs from NLEM from the recommended values

Efficacy of vijaysar, aloevera alone and their combination in the treatment of newly diagnosed cases of type 2 diabetes mellitus: a randomized single blind prospective study

Background: Diabetes mellitus is a disease was known since ancient time and all system of medicine over world were tried to cure this disease. Unfortunately the numbers of diabetes patients are increasing day by day due to many risk factors such as sedentary life, obesity etc.Methods: A total of 120 patients with newly diagnosed type 2 diabetes mellitus attending OPD of UPUMS, Saifai, Etawah, Uttar Pradesh, India, were included in the study. Patients were divided into 4 groups. Group-1, 2, 3 and 4 received Aloevera, Vijaysar, Aloevera + Vijaysar and Glimepiride respectively for thirteen weeks. Sample for fasting blood sugar and postprandial blood sugar were measured at baseline, 1st, 2nd, 3rd, 5th, 8th and at 13th week. HbA1c and Lipid profile were measured at baseline and at thirteen week.Results: Significant decrease in FPG, 2hPG, and HbA1c level were achieved in all groups but effects was maximum in Glimepiride group. Vijaysar had shown better glucose control than Aloevera as well as Aloevera + Vijaysar group. Synergism was shown by both herbal drugs for FPG control but not for 2hPG. The Effect of Vijaysar alone on 2hPG was similar to Glimepiride.Conclusions: Vijaysar could be a promising herbal drug for the treatment of mild uncomplicated cases of type-2 diabetes mellitus; however both drugs have shown synergism for FPG control. Both herbal drugs were safe during our study, only one patient of Vijaysar group had complaint of diarrhoea, which was subsided one week later

Development of Shoot Cultures from Leaf Explant of Portulaca quadrifida L.

Portulaca quadrifida (Portulacaceae) is an annual succulent herb having medicinal value and is consumed as a vegetable or salads in India. In the present study, leaf explants were inoculated on Murashige and Skoog’s (MS) medium fortified with sucrose (3%) and combinations of N6-benzyladenine (6-BA) and kinetin (KIN) individually and in combination with 1-naphtalene acetic acid (NAA). Rapid regeneration was observed in medium fortified with combinations of 6-BA (8 µM) and NAA (1 µM) which formed 19.40 ± 0.64 shoots with 100% response. Variation in sucrose concentrations (4-6%) was tried but it failed to increase the shoot number. When the optimized medium was fortified with different carbon sources viz. dextrose, glucose and maltose, they could not evoked better response and sucrose proved to be more effective for regeneration. Rooting of in vitro shoots was achieved in ½MS + sucrose (1%) + indole-3-butyric acid (IBA, 2 µM)

A study of practical aspects of menstrual hygiene -A Rural community based study

Method: Data collection regarding their current knowledge about menstruation & menstrual hygiene was collected by using a pre-tested questionnaire. Topics included-concerning menstruation, source of information, menstrual hygiene. This was explained to the girls going to school in their classroom after taking permission from the school authority. Result : 1. The mean age -14.5 yrs, Minimum age -11 yrs, Maximum age -20yrs 2. Menstrual related problem--Regular menstrual cycle -73% Nature of bleeding -Moderate -64 %, Heavy -22 %, Scanty -14 % 3. Other complaints during menstrual cycleAbdominal pain -59.25 %, Giddiness -15%, Nausea and vomiting -18 %, Generalised weakness -47 % girls, White discharge -22 % 4. Menstrual hygiene Taking regular bath.-90 %, Cleaning of external genitals-77 %, Use of clothes -35%, Sanitary napkins -65 %. Nutrition - According to B.M.I.-55.55 % in healthy and 44.45% were underweight group

Evaluation of antidepressant and analgesic activity of tapentadol with mirtazapine: an experimental study

Background: Data comparing tapentadol with an antidepressant is limited. A comparison of tapentadol with mirtazapine at different dose has not been performed, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that tapentadol should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a study evaluate antidepressant and analgesic activity of tapentadol with mirtazapine at different doses in Swiss albino mice.Methods: Tapentadol was administered at 10, 20 and 40 mg/kg (i.p) once daily for 14 days to swiss albino mice of either sex. The immobility period for antidepressant activity of mice were recorded in forced swim test and reaction time for analgesic activity of mice were recorded in tail flick test of the control and drug treated group. The antidepressant and analgesic activity of tapentadol (10, 20, 40 mg/kg i.p) was compared with that of mirtazapine (3, 5, 7 mg/kg i.p), administered for 14 days.Results: Tapentadol produced better antidepressant at (20, 40 mg/kg), but less at 10 mg/kg and significant analgesic activity at all the three doses, as indicated by reduction in immobility times and increase in reaction time as compared to control. Mirtazapine produced no antinociceptive activity at 3 mg/kg, but significant at 5, 7 mg/kg and showed better antidepressant activity at all the three doses in mice. The result of this study indicates the better analgesic activity of tapentadol at all the doses and least antidepressant activity at 10 mg/kg, as compared to mirtazapine which has shown better antidepressant activity at all the three doses but no analgesic activity at 3 mg/kg.Conclusion: It can be concluded that tapentadol is a better drug in case of depression associated with pain compared to mirtazapine in mice

Feasibility assessment of crowdsourcing slogans for promoting household waste segregation in India: a cross-sectional study

IntroductionCrowdsourcing is an emerging technique to engage or access a wider set of experts and multiple stakeholders through online platforms, which might effectively be employed in waste management. Therefore, we assessed the feasibility of the crowdsourcing method to provide an alternative approach that can improve household waste segregation using an “online-slogan-contest”.MethodsThe contest was promoted via targeted emails to various governmental and non-governmental organizations and through social media platforms for around 4 weeks (25 days). The entries were received through a Google form. The slogans were assessed by the experts and analyzed using content analysis methods.ResultsTotal 969 entries were received from different geographic regions in India. Of that, 456 were in English and 513 in Hindi. Five themes of waste segregation emerged from the received slogans: (1) Community awareness, responsibility, and support, (2) Significance of household waste segregation, (3) Use of separate dustbins, (4) Health and well-being, and (5) Environment and sustainability.DiscussionCrowdsourcing approaches can be used by local authorities for improving waste management approaches and are recommended as these involve a wider audience within a short time frame. Moreover, this approach is flexible and integrating crowdsourcing approaches strengthens our understanding of existing waste management activities

Mechanosensing is critical for axon growth in the developing brain.

During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain. Retinal ganglion cell axons grew toward softer tissue, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically and knocked down the mechanosensitive ion channel piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness, read out by mechanosensitive ion channels, is critically involved in instructing neuronal growth in vivo.This work was supported by the German National Academic Foundation (scholarship to D.E.K.), Wellcome Trust and Cambridge Trusts (scholarships to A.J.T.), Winston Churchill Foundation of the United States (scholarship to S.K.F.), Herchel Smith Foundation (Research Studentship to S.K.F.), CNPq 307333/2013-2 (L.d.F.C.), NAP-PRP-USP and FAPESP 11/50761-2 (L.d.F.C.), UK EPSRC BT grant (J.G.), Wellcome Trust WT085314 and the European Research Council 322817 grants (C.E.H.); an Alexander von Humboldt Foundation Feodor Lynen Fellowship (K.F.), UK BBSRC grant BB/M021394/1 (K.F.), the Human Frontier Science Program Young Investigator Grant RGY0074/2013 (K.F.), the UK Medical Research Council Career Development Award G1100312/1 (K.F.) and the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R21HD080585 (K.F.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nn.439

3D genomics across the tree of life reveals condensin II as a determinant of architecture type

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional(3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedlyduring eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with theabsence of condensin II subunits. Moreover, condensin II depletion converts the architecture of thehuman genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state,centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physicalmodel in which lengthwise compaction of chromosomes by condensin II during mitosis determineschromosome-scale genome architecture, with effects that are retained during the subsequent interphase.This mechanism likely has been conserved since the last common ancestor of all eukaryotes.C.H. is supported by the Boehringer Ingelheim Fonds; C.H., Á.S.C., and B.D.R. are supported by an ERC CoG (772471, “CohesinLooping”); A.M.O.E. and B.D.R. are supported by the Dutch Research Council (NWO-Echo); and J.A.R. and R.H.M. are supported by the Dutch Cancer Society (KWF). T.v.S. and B.v.S. are supported by NIH Common Fund “4D Nucleome” Program grant U54DK107965. H.T. and E.d.W. are supported by an ERC StG (637597, “HAP-PHEN”). J.A.R., T.v.S., H.T., R.H.M., B.v.S., and E.d.W. are part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. Work at the Center for Theoretical Biological Physics is sponsored by the NSF (grants PHY-2019745 and CHE-1614101) and by the Welch Foundation (grant C-1792). V.G.C. is funded by FAPESP (São Paulo State Research Foundation and Higher Education Personnel) grants 2016/13998-8 and 2017/09662-7. J.N.O. is a CPRIT Scholar in Cancer Research. E.L.A. was supported by an NSF Physics Frontiers Center Award (PHY-2019745), the Welch Foundation (Q-1866), a USDA Agriculture and Food Research Initiative grant (2017-05741), the Behavioral Plasticity Research Institute (NSF DBI-2021795), and an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375). Hi-C data for the 24 species were created by the DNA Zoo Consortium (www.dnazoo.org). DNA Zoo is supported by Illumina, Inc.; IBM; and the Pawsey Supercomputing Center. P.K. is supported by the University of Western Australia. L.L.M. was supported by NIH (1R01NS114491) and NSF awards (1557923, 1548121, and 1645219) and the Human Frontiers Science Program (RGP0060/2017). The draft A. californica project was supported by NHGRI. J.L.G.-S. received funding from the ERC (grant agreement no. 740041), the Spanish Ministerio de Economía y Competitividad (grant no. BFU2016-74961-P), and the institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687). R.D.K. is supported by NIH grant RO1DK121366. V.H. is supported by NIH grant NIH1P41HD071837. K.M. is supported by a MEXT grant (20H05936). M.C.W. is supported by the NIH grants R01AG045183, R01AT009050, R01AG062257, and DP1DK113644 and by the Welch Foundation. E.F. was supported by NHGR