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Maintenance of immune homeostasis is an intricate process wherein inflammasomes play a pivotal role by contributing to innate and adaptive immune responses. Inflammasomes are ensembles of adaptor proteins that can trigger a signal following innate sensing of pathogens or non-pathogens eventuating in the inductions of IL-1β and IL-18. These inflammatory cytokines substantially influence the antigen-presenting cell's costimulatory functions and T helper cell differentiation, contributing to adaptive immunity. As acute and chronic disease conditions may accompany parallel tissue damage, we analyze the critical role of extracellular factors such as cytokines, amyloids, cholesterol crystals, etc., intracellular metabolites, and signaling molecules regulating inflammasome activation/inhibition. We develop an operative framework for inflammasome function and regulation by host cell factors and pathogens. While inflammasomes influence the innate and adaptive immune components' interplay modulating the anti-pathogen adaptive immune response, pathogens may target inflammasome inhibition as a survival strategy. As trapped between health and diseases, inflammasomes serve as promising therapeutic targets and their modus operandi serves as a scientific rationale for devising better therapeutic strategies.

Chlamydia trachomatis and human papilloma virus (HPV) are the two most common sexually transmitted infections among women. HPV infection can increase the risk of cervical cancer and infertility while C. trachomatis induces pelvic inflammatory disease. Here, we elucidate the molecular conundrum of the co-infection of HPV and C. trachomatis infection and their outcome with respect to cervical cancer. HPV infection was mimicked by overexpression of HPV 16 E6-E7 or using human cervical cell lines SiHa and C33a (with and without HPV 16 respectively). HPV transfected co-infection increased cell proliferation and resistance to H

Macrophages are one of the first innate immune cells to reach the site of infection or injury. Diverse functions from the uptake of pathogen or antigen, its killing, and presentation, the release of pro- or anti-inflammatory cytokines, activation of adaptive immune cells, clearing off tissue debris, tissue repair, and maintenance of tissue homeostasis have been attributed to macrophages. Besides tissue-resident macrophages, the circulating macrophages are recruited to different tissues to get activated. These are highly plastic cells, showing a spectrum of phenotypes depending on the stimulus received from their immediate environment. The macrophage differentiation requires colony-stimulating factor-1 (CSF-1) or macrophage colony-stimulating factor (M-CSF), colony-stimulating factor-2 (CSF-2), or granulocyte-macrophage colony-stimulating factor (GM-CSF) and different stimuli activate them to different phenotypes. The richness of tissue macrophages is precisely controlled via the CSF-1 and CSF-1R axis. In this review, we have given an overview of macrophage origin via hematopoiesis/myelopoiesis, different phenotypes associated with macrophages, their clinical significance, and how they are altered in various diseases. We have specifically focused on the function of CSF-1/CSF-1R signaling in deciding macrophage fate and the outcome of aberrant CSF-1R signaling in relation to macrophage phenotype in different diseases. We further extend the review to briefly discuss the possible strategies to manipulate CSF-1R and its signaling with the recent updates.

Chlamydia trachomatis (C.tr), an obligate intracellular pathogen, causes asymptomatic genital infections in women and is also a leading cause of preventable blindness. Limited mouse model of chronic C.tr infection are available to study the host immune response. We have developed in vivo mice models of acute and chronic infections for C. trachomatis to explore the significance of macrophage-directed response in mediating immune activation/suppression. During chronic and repeated infections, IFNγ secretion from T cells is abated while TGFβ and IL-10 secretion is enhanced. An increase in exhaustion (PD1, CTLA4) and anergic (Klrg3, Tim3) T cell markers is also observed during chronic infection. It was observed that alternatively-activated macrophages with low CD40 expression promote Th2 and Treg differentiation and lead to sustained C. trachomatis genital infection. Macrophages infected with C. trachomatis or treated with supernatant of infected epithelial cells drive them to alternately-activated phenotype. C. trachomatis infection prevents increase in CD40 expression. Low IFNγ, as observed in chronic infection leads to incomplete clearance of bacteria and poor immune activation. C. trachomatis decapacitates IFNγ responsiveness in macrophages via hampering IFNγRI and IFNγRII expression which can be correlated with poor expression of MHC-II, CD40, iNOS and NO release even following IFNγ supplementation. Alternatively-activated macrophages during C. trachomatis infection express low CD40 rendering immunosuppressive, Th2 and Treg differentiation which could not be reverted even after IFNγ supplementation. The alternative macrophages also harbour high bacterial load and are poor responders to IFNγ, thus promoting immunosupression. Thus, C. trachomatis modulate the innate immune cells attenuating the anti-chlamydial functions of T cells in a manner that involves decreased CD40 expression on macrophages.

The underlined paper aimed at taking transgender individual disclosure decisions in a workplace to be a matter of socio-cultural dynamics. Hence, the place of transgender individuals, defined by th...

Infrastructure is one of the most crucial pillars of productivity in any economy. Pushing infrastructure development and particularly organizing funds for infrastructure projects have been the biggest challenge in developing nations. The present study was taken up to review the infrastructure development and its financing in India. The study intended to (1) study the infrastructure development in India in the 11th and 12th Five Year Plan, (2) examine the sources used for infrastructure financing in India, (3) assess the actions taken by government to facilitate infrastructure financing and (4) propose measures to augment infrastructure financing to overcome infrastructure deficit in the country. It was found that though Government of India and Reserve Bank of India have taken several initiatives to facilitate infrastructure financing, there still exists a vast gap between supply side and the demand side. Some of the recommendations given in the paper include the need to evolve innovative business models and mitigate administrative glitches to ensure larger private participation; exploit the untapped potential of diaspora; revisit the statutory liquidity ratio norms for banks; evolve the municipal bond market; boost regional integration and improved connectivity through creation of corridors between sub-continental regions, which would not only bridge the finance gap but also the knowledge gap, etc.

A series of deoxycholic acid-chalcone amides were synthesised and tested against the human lung cancer cell line, A549 and the cervical cancer cell line, SiHa. Among the synthesised deoxycholic acid-chalcone conjugates, some conjugates showed encouraging results as anticancer agents with good in vitro activity. More precisely, deoxycholic acid-chalcone conjugates 4b (IC50: 0.51 μM) and 4e (IC50: 0.84 μM) having 2‑nitrophenyl and 3,4,5‑trimethoxyphenyl groups exhibited a good activity against human cancer cell-line SiHa and while 4d (IC50: 0.25 μM) and 4b (IC50: 1.71 μM) showed better activity against A549 lung cancer cell line with respect to deoxycholic acid and chalcones. The anticancer activity of the bile acid conjugated chalcones was more than the activity of chalcone and deoxycholic acid alone. The results indicate that a bile acid conjugate strategy may be beneficial in improving the biological activity of chalcone derivatives. The enhanced activity of certain compounds may be due to their increased bioavailability.

Cellular communication mediated by cytokines is an important mechanism dictating immune responses, their cross talk and final immune output. Cytokines play a major role in dictating the immune outcome to cancer by regulating the events of development, differentiation and activation of innate immune cells. Cytokines are pleiotropic in nature, hence understanding their role individually or as member of network cytokines is critical to delineate their role in tumour immunity. Tumour systemically manipulates the immune system to evade and escape immune recognition for their uncontrollable growth and metastasis. The developing tumour comprise a large and diverse set of myeloid cells which are vulnerable to manipulation by the tumour-microenvironment. The innate immune cells of the monocytic lineage skew the fate of the adaptive immune cells and thus dictating cancer elimination or progression. Targeting cells at tumour cite is preposterous owing to their tight network, poor reach and abundance of immunosuppressive mechanisms. Monocytic lineage-derived cytokines (monokines) play crucial role in tumour regression or progression by either directly killing the tumour cells with TNFα or promoting its growth by TGFβ. In addition, the monokines like IL-12, IL-1β, IL-6, IL-10 and TGFβ direct the adaptive immune cells to secrete anti-tumour cytokines, TNFα, IFNγ, perforin and granzyme or pro-tumour cytokines, IL-10 and TGFβ. In this review, we elucidate the roles of monokines in dictating the fate of tumour by regulating responses at various stages of generation, differentiation and activation of immune cells along with the extensive cross talk. We have attempted to delineate the synergy and antagonism of major monokines among themselves or with tumour-derived or adaptive immune cytokines. The review provides an update on the possibilities of placing monokines to potential practical use as cytokine therapy against cancer.

During Aspergillus fumigatus mediated lung inflammation, NLRP3 inflammasome is rapidly activated that aggravates IL-1β production contributing to lung inflammation. Previously, we have shown the protective role of SYK-1 inhibition in inhibiting inflammasome activation during lung inflammation. In the current manuscript, we explored the protective role of direct caspase-1 inhibition during β-glucan-induced lung inflammation. We have mimicked the lung inflammation by administering intranasal β-glucan in mice model. YVAD was used for caspase-1 inhibition. We have shown that caspase-1 inhibition by YVAD did not alter inflammasome independent inflammatory cytokines, while it significantly reduced inflammasome activation and IL-1β secretion. Caspase-1 inhibited bone marrow derived dendritic cells (BMDCs), co-cultured with T cells showed decreased T-cell proliferation and direct them to secrete high TGF-β and IL-10 compared to the T cells co-cultured with β-glucan primed dendritic cells. Caspase-1 inhibition in BMDCs also induced IL-22 secretion from CD4+T cells. Caspase-1 inhibition in intranasal β-glucan administered mice showed decreased tissue damage, immune cell infiltration and IgA secretion compared to control mice. Further, splenocytes challenged with β-glucan show high IL-10 secretion and increased FOXp3 and Ahr indicating an increase in regulatory T cells on caspase-1 inhibition. Caspase-1 inhibition can thus be an attractive target to prevent inflammation mediated tissue damage during Aspergillus fumigatus mouse model and can be explored as an attractive therapeutic strategy.HIGHLIGHTSCaspase-1 inhibition protects lung damage from inflammation during β-glucan exposureCaspase-1 inhibition in dendritic cells decreases IL-1β production resulting in decreased pathogenic Th17Caspase-1 inhibition promotes regulatory T cells thereby inhibiting lung inflammation Caspase-1 inhibition protects lung damage from inflammation during β-glucan exposure Caspase-1 inhibition in dendritic cells decreases IL-1β production resulting in decreased pathogenic Th17 Caspase-1 inhibition promotes regulatory T cells thereby inhibiting lung inflammation

Objective: Strategic storytelling can be used to reframe dominant cultural narratives and improve community health outcomes. This pilot study assessed the impact of an original, online 3-week e-course, delivered from November to December 2021, in increasing learners’ knowledge of and concern for the seriousness of skin-shade discrimination and the use of skin-lightening products in India, increasing learners’ understanding of storytelling-based communication techniques for public health promotion, and increasing learners’ intentions to use strategic storytelling for social change. Design, Setting and Method: The course used case-method pedagogy to address colourism and cosmetic skin lightening. Learners ( N = 25) completed a pre-course baseline survey on their knowledge and concerns regarding colourism and the use of skin-lightening products, as well as their expectations and interests in taking the course. Following course completion, learners completed a post-webinar survey. The Wilcoxon Signed-Rank test was used to assess differences from pre- to post-course surveys on quantitative items. Open-ended responses were also analysed using qualitative content analysis for recurring themes on learner interest and experience. Results: From pre- to post-course surveys, there were significant improvements in learners’ knowledge of skin shade discrimination and the use of skin-lightening products ( p < .05). Learners indicated being more concerned about the seriousness of skin shade discrimination post-course compared to pre-course. Learners also described a positive learning experience and indicated that the e-course enhanced their understanding of strategic storytelling. Conclusion: Findings highlight the importance of an original e-course that uses case-method pedagogy to build knowledge and skills that addresses the impacts of colourism on the health of Indian adolescents and provides new directions for future research on health education interventions that aim to tackle colourism.

Berberine is a plant-derived alkaloid with potent anti-cancer activities. Berberine may redirect the tumor-promoting immunosuppressive M2 macrophages, to tumoricidal activated M1 macrophages. But such an anti-tumor function remains to be demonstrated.Polarization of macrophages to an immunosuppressive phenotype within the tumor microenvironment promotes tumor growth and contributes to resistance to chemotherapy. We examined if berberine would target macrophage polarization to reinstate anti-tumor immune response.Using a B16F10 mouse melanoma model, we assessed berberine-induced re-polarization of immunosuppressive M2 macrophages to anti-tumor M1 macrophages and subsequent T-cell activation within the immunosuppressive tumor microenvironment.The B16F10 culture supernatant along with tumor antigen was used as tumor mimicking conditioned medium (CM). The bone marrow-derived macrophages were cultured in CM for 5 days. The CM-induced skewing of macrophages to M2-like phenotype was confirmed by flow cytometry and ELISA. The T-cells were co-cultured with macrophages to decipher the effect of berberine on T-cell differentiation. In vivo efficacy of berberine was analyzed using melanoma model of solid tumor.Berberine inhibited rIL-6-induced STAT-3 phosphorylation and IL-10 release from B16F10 cells. It enhanced tumor antigen-induced IL-1β, IL-12 and TNFα, but suppressed IL-6 and TGF-β release. Berberine significantly prevented the tumor antigen-mediated IL-10-enhanced IL-6 and TGF-β expression. The CM skewed the bone marrow-derived macrophages to CD206-high but MHC-II-low M2-like tumor-associated macrophages. Berberine partially prevented the generation of these macrophages and was associated with reduced C/EBPβ and Egr2 mRNA expression and lowered IL-10 and TGF-β production. Berberine significantly reduced Arginase-1 expression in CM-treated M1 and M2-like macrophages. Berberine increased MHC-II and CD40 expression on the macrophages augmenting the CTL activity and the number of IFNγ-producing CD4These data indicate that berberine interferes with pro-tumor macrophage polarization and IL-10 and TGF-β release but restores Tcell anti-tumor cytotoxicity in the tumor microenvironment.

Corporate governance is a significant tool to build strong and long relationships among various stakeholders in kinds of business organizations. Family businesses are not an exception to this. Like any other businesses, family businesses also need to have governance in place and practice to achieve the business strategies and to have long-term succession. Family-owned businesses are the backbone of many countries' economies in the world contributing substantial portion of GDP. Considering these, it is important to know the best practices of governance in family owned business organizations and the role played by governance to improve the strengths of these businesses. The chapter throws light on family business governance and explores various important practices highlighting their advantages and disadvantages in detail.

The last few decades have witnessed serious sustainability challenges such as economic uncertainty, depletion ozone layer, increase in pollution, urban decay, overpopulation, degradation, and shortage of natural resources, etc. The increasing pace of change and rising competition has posed unknown challenges and unparalleled pressure on the corporates not only to prosper, but also to sustain in future. With customers, investors, and other stakeholders becoming increasing aware and critical about sustainable practices, the companies are forced to think past short term monetary gains. As there exists an interdependence, integration, and co-creation among the three basic tenets of sustainability-people, planet, and profits. There is a global call on companies to pursue socially responsible conduct and adopt innovative practices which create value for people, planet, as well as economy.

In recent years, many organizations have incorporated corporate social responsibility (CSR) as part of their vision and mission statements. There are many evidences demonstrates the positive results after implementation of CSR. Now, the question is, what are the contributions of CSR towards sustainable development of society and growth? The current study shows the association between CSR and sustainable growth. Real-time analysis of relevant studies of organizations who initiated CSR strategies towards sustainable development and growth are incorporated in the present chapter.

Development is an irreversible process of differentiating the undifferentiated cells to functional cells. Brain development involves generation of cells with varied phenotype and functions, which is limited during adulthood, stress, damage/degeneration. Cellular reprogramming makes differentiation reversible process with reprogramming somatic/stem cells to alternative fate with/without stem cells. Exogenously expressed transcription factors or small molecule inhibitors have driven reprogramming of stem/somatic cells to neurons providing alternative approach for pre-clinical/clinical testing and therapeutics. Here in, we report a novel approach of microRNA (miR)-induced trans-differentiation of macrophages (CD11b high) to induced neuronal cells (iNCs) (neuronal markers high-Nestin, Nurr1, Map2, NSE, Tubb3 and Mash1) without exogenous use of transcription factors. miR 9, 124, 155 and 224 successfully transdifferentiated macrophages to neurons with transient stem cell-like phenotype. We report trans differentiation efficacy 18% and 21% with miR 124 and miR 155. in silico (String 10.0, miR gator, mESAdb, TargetScan 7.0) and experimental analysis indicate that the reprogramming involves alteration of pluripotency genes like Oct4, Sox2, Klf4, Nanog and pluripotency miR, miR 302. iNCs also shifted to G0 phase indicating manipulation of cell cycle by these miRs. Further, CD133+ intermediate cells obtained during current protocol could be differentiated to iNCs using miRs. The syanpsin+ neurons were functionally active and displayed intracellular Ca+2 evoke on activation. miRs could also transdifferentiate bone marrow-derived macrophages and peripheral blood mononuclear cells to neuronal cells. The current protocol could be employed for direct in vivo reprogramming of macrophages to neurons without teratoma formation for transplantation and clinical studies.HighlightsmiR 9, miR 124 and miR155 could reprogramme macrophages to mature neurons.miR-induced neuronal reprogramming involves stem cell like intermediate phenotype.Graphical AbstractMacrophages transfected with miR 9, 124, 155 and 224 alter pluripotency genes and neuronal differentiation genes via various mechanisms as elucidated. NIM components may also manipulate driving neuronal differentiation gene expression inducing formation of neuronal cells.

It is well acknowledged fact thatentrepreneurship is an engine of economic growth and social development. Women entrepreneurship though has been growing around the world, but the evidences suggest that women entrepreneurscontinue to be adversely affected by the numerous socio-economic issues in the male dominated business societies, which hugely undermine the morale of women entrepreneurs.The current study was taken up to investigate the working of twenty sevenwomen entrepreneurs working on micro and small levels, in different areas of Uttar Pradesh (India), who have created employment opportunities for thousands of people living at grass root level and also created new prospects for the rural artisans in theirregion. The study aims to explore the various the obstacles faced by the women entrepreneurs working in different areas of Uttar Pradesh (India),analyze the impact of the prevailing constraints and challenges on the progress of these women entrepreneurs, and recommend the aspects that he to be looked into by the policy makers, to address the issues and challenges. It is also anticipated that the findings will bring to light valuable insights, which might be used by the policymakers, organization and institutions who intend to assist more and more entrepreneurs, especially women entrepreneurs, to venture into businesses. The study revealed multifarious constraints and challenges faced by the women during their entrepreneurial journey. In the current study we have tried to classify these constraints into four broad categories: Socio-Cultural Issues; Economic Issues; Psychological Issues and Managerial Issues.

We report for the very first time the discovery of amyloid-like self-assemblies formed by the nonaromatic single amino acids cysteine (Cys) and methionine (Met) under neutral aqueous conditions. The structure formation was assessed and characterized by various microscopic and spectroscopic techniques such as optical microscopy, phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy. The mechanism of self-assembly and the role of hydrogen bonding and thiol interactions of Cys and Met were assessed by Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and solid state NMR along with various control experiments. In addition, molecular dynamics simulations were carried out to gain insight into assembly initiation. Further, Thioflavin T and Congo red binding assays with Cys and Met structures indicated that these single amino acid assemblies may have amyloid-like characteristics. To understand the biological significance of the Cys and Met structures, cytotoxicity assays of the assemblies were performed on human neuroblastoma IMR-32 cells and monkey kidney cells (COS-7). The results revealed that both Cys and Met fibers were cytotoxic. The cell viability assay further supported the hypothesis that aggregation of single amino acid may contribute to the etiology of metabolic disorders like cystinuria and hypermethioninemia. The results presented in this study are striking, and to the best of our knowledge this is the first report which demonstrates that nonaromatic amino acids like Cys and Met can undergo spontaneous self-assembly to form amyloidogenic aggregates. The results presented are also consistent with the established generic amyloid hypothesis and support a new paradigm for the study of the etiology of single amino acid initiated metabolic disorders in amyloid related diseases.

The present study was taken up to review the initiatives taken by the present government to further consolidate the efforts to promote inclusive and sustainable economic growth in India and to sustain the existing growth. The intent of the study was to explore the measures taken by the government to enhance: (a) infrastructure development, (b) financial inclusion, (c) growth in agriculture and rural sector, (d) social inclusion, (e) good governance and policy reforms and (f) expertise development and job creation in the country. The aim was also to evaluate the impact of these initiatives on the economy, find the gaps, if any, and suggest measures to complement the on-going efforts.

Repeated exposure to the fungal pathogen Aspergillus fumigates triggers spleen tyrosine kinase (SYK) signalling through dectin-1 activation, which is associated with deleterious airway inflammation. β-Glucan-induced dectin-1 signalling activates the NLRP3 inflammasome, which in turn rapidly produces IL-1β, a master regulator of inflammation. IL-1β expression results in Th17/Treg imbalance, pulmonary inflammation, and bystander tissue injury. This study reports that 3,4 methylenedioxy-β-nitrostyrene (MNS), a potent SYK inhibitor, markedly decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines in vitro. Furthermore, SYK inhibition markedly decreased β-glucan-induced IL-1β expression, suggesting that SYK is indispensable for NLRP3 inflammasome activation. Decreased IL-1β expression correlated with reduced Th17 response and enhanced immunosuppressive Treg response. Notably, SYK inhibition ameliorated inflammation caused by repeated intranasal β-glucan challenge in BALB/C mice. SYK inhibition also restored the Th17/Treg balance via decreased Th17 and increased Treg responses, as evidenced by decreased IL-17 and ror-γ levels. Additionally, inhibition of SYK increased IL-10 secreting CD4+FOXP3+ T cells that accompanied reduced T cell proliferation. Decreased IgA in the Bronchoalveolar lavage (BAL) fluid and serum also indicated the immunosuppressive potential of SYK inhibition. Histopathology data revealed that repeated β-glucan challenge caused substantial pulmonary damage, as indicated by septal thickening and interstitial lymphocytic, neutrophil and granulocyte recruitment. These processes were effectively prevented by SYK inhibition, resulting in lung protection. Collectively, our findings suggest that SYK inhibition ameliorates dectin-1- mediated detrimental pulmonary inflammation and subsequent tissue damage. Therefore, SYK can be a new target gene in the therapeutic approach against fungal induced airway inflammation.

Development is an irreversible process of differentiating the undifferentiated cells to functional cells. Brain development involves generation of cells with varied phenotype and functions, which is limited during adulthood, stress, damage/degeneration. Cellular reprogramming makes differentiation reversible process with reprogramming somatic/stem cells to alternative fate with/without stem cells. Exogenously expressed transcription factors or small molecule inhibitors have driven reprogramming of stem/somatic cells to neurons providing alternative approach for pre-clinical/clinical testing and therapeutics. Here in, we report a novel approach of microRNA (miR)- induced trans-differentiation of macrophages (CD11b high) to induced neuronal cells (iNCs) (neuronal markershigh- Nestin, Nurr1, Map2, NSE, Tubb3 and Mash1) without exogenous use of transcription factors. miR 9, 124, 155 and 224 successfully transdifferentiated macrophages to neurons with transient stem cell-like phenotype. We report trans differentiation efficacy 18% and 21% with miR 124 and miR 155. in silico(String 10.0, miR gator, mESAdb, TargetScan 7.0) and experimental analysis indicate that the reprogramming involves alteration of pluripotencygenes like Oct4, Sox2, Klf4, Nanog and pluripotency miR, miR 302. iNCs also shifted to G0 phase indicating manipulation of cell cycle by these miRs. Further, CD133+ intermediate cells obtained during current protocol could be differentiated to iNCs using miRs. The syanpsin+ neurons were functionally active and displayed intracellular Ca+2 evoke on activation. miRs could also transdifferentiate bone marrow-derived macrophages and peripheral blood mononuclear cells to neuronal cells. The current protocol could be employed for direct in vivo reprogramming of macrophages to neurons without teratoma formation for transplantation and clinical studies.

Background Berberine, a plant alkaloid, has been used since many years for treatment of gastrointestinal disorders. It also shows promising medicinal use against metabolic disorders, neurodegenerative disorders and cancer; however its efficacy in neuroblastoma (NB) is poorly explored. Hypothesis EMT is important in cancer stemness and metastasis resulting in failure to differentiate; thus targeting EMT and related pathways can have clinical benefits. Study design Potential of berberine was investigated for (i) neuronal differentiation and cancer stemness inhibition, (ii) underlying molecular mechanisms regulating cancer-stemness and (iii) EMT reversal. Methods Using neuro2a (N2a) neuroblastoma cells (NB); we investigated effect of berberine on neuronal differentiation, cancer-stemness, EMT and underlying signalling by immunofluorescence, RT-PCR, Western blot. High glucose-induced TGF- β mediated EMT model was used to test EMT reversal potential by Western blot and RT-PCR. STRING analysis was done to determine and validate functional protein-interaction networks. Results We demonstrate berberine induces neuronal differentiation accompanying increased neuronal differentiation markers like MAP2, β-III tubulin and NCAM; generated neurons were viable. Berberine attenuated cancer stemness markers CD133, β- catenin , n-myc, sox2, notch2 and nestin. Berberine potentiated G0/G1 cell cycle arrest by inhibiting proliferation, cyclin dependent kinases and cyclins resulting in apoptosis through increased bax/bcl-2 ratio. Restoration of tumor suppressor proteins, p27 and p53, indicate promising anti-cancer property. The induction of NCAM and reduction in its polysialylation indicates anti-migratory potential which is supported by down regulation of MMP-2/9. It increased epithelial marker laminin and smad and increased Hsp70 levels also suggest its protective role. Molecular insights revealed that berberine regulates EMT via downregulation of PI3/Akt and Ras-Raf-ERK signalling and subsequent upregulation of p38-MAPK. TGF- β secretion from N2a cells was potentiated by high glucose and negatively regulated by berberine through modulation of TGF- β receptors II and III. Berberine reverted mesenchymal markers, vimentin and fibronectin, with restoration of epithelial marker E-cadherin, highlighting the role of berberine in reversal of EMT. Conclusion Collectively, the study demonstrates prospective use of berberine against neuroblastoma as elucidated through inhibition of fundamental characteristics of cancer stem cells: tumorigenicity and failure to differentiation and instigates reversal in the EMT.

The term democracy is the Hindi version of English democracy, for which the words democracy, democracy, democracy etc. are also used, which means - a mechanism or system in which the people have sovereignty. It is an undeniable truth that economic inequality is the root of all difficulties. Due to this, the world is deranged and frustrated and for this reason, since ancient times in India, mystics dreamed to remove the economic disparity between humans. Democracy is one such vision in which workers, peasants and helpless victims come together to play the role of their true partner. जनवाद शब्द अंग्रेजी के डेमोक्रेसी का हिंदी प्रतिरूप है, जिसके लिए जनतंत्र, लोकतंत्र, लोकशाही आदि शब्दों का भी प्रयोग किया जाता है, जिसका अर्थ है - एक ऐसा तंत्र या व्यवस्था जिसमें जनता की संप्रभुता हो।यह निर्विवाद सत्य है कि आर्थिक विषमता सभी कठिनाइयों की जड़ हैं। इसके कारण संसार विश्रृंखलित एवं कंुठित होता है और इसी कारण भारत में प्राचीन काल से ही मनीषियों ने मानव-मानव के मध्य आर्थिक विषमता को दूर करने का स्वप्न देखा। जनवाद एक ऐसी ही दृष्टि है जिसमें मजदूरों, किसानों, असहाय पीड़ितों को एक जुट कर उनके सच्चे साथी की भूमिका निभाती है।

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. To get insights into the structure formation, thioflavin T and Congo red binding assays were done which revealed that aggregates may not have amyloid like characteristics. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. The cytotoxicity assays of cysteine and methionine structures were performed on Human Neuroblastoma IMR-32 cells which suggested that aggregates are not cytotoxic in nature and thus, may not have amyloid like etiology. The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.

The part that Micro, Small and Medium Enterprises (MSMEs) play, both in developed and developing countries, cannot be over emphasized and therefore their existence and survival is a matter of concern not only for the policy makers but also for the researchers. Large number of MSMEs die the same year that they are established. The current research was taken up to understand how MSMEs manage their risk and whether enterprise risk management is essential for survival and sustainable development of MSMEs. The objective of the research was to (1) understand the peculiar nature of the MSMEs which make them vulnerable, (2) explore the various risks confronted by MSMEs, (3) understand how the MSMEs manage their risk, (4) understand 'Enterprise Risk Management' and its components and (5) explore the relevance of 'Enterprise Risk Management' for the survival and sustainable development of MSMEs. The results show that MSMEs by virtue of their size, inadequate resources and restricted know-how generally confront wide-ranging risks. In MSMEs the management of risk is concentrated in the hands of the owner-managers and there are no systemic linkages between the planning and risk management. Therefore, this study stresses the need for integrating an effective enterprise risk management system with planning and administration within the MSMEs, to avoid fatal consequences.

This case study showcases the initiative and hard work of a women entrepreneur from India, who had a passion to guide and counsel the young graduates towards their professional education. This case study discusses in detail the education acquired by the entrepreneur, her vision, initiative, development and operation of her venture, major impediments that came her way, measures adopted by her to overcome them and her plans for future expansion and growth. It also showcases how the women entrepreneur was successful in creating several new jobs in the society, besides assisting the youth to take up their desired career path.

Ethnopharmacological relevance Iridoid glycosides have been associated with decreased risks of cancer, such as hepatocarcinoma. Although Picrorrhiza kurroa has shown activity against hepatocarcinogenesis, its mechanism of action is poorly understood, further the anticancer activity of iridoid glycosides present in this plant has not been tested so far. Aim of the study Here, MCF-7 cell lines (Human breast cancer) were used to test whether P. kurroa extract (PE) and its isolated iridoid glycosides Picroside I (PS), Kutkoside (KS), and Kutkin (KT) exerts the anti-invasion activity via down-regulation of the expression of matrix metalloproteinases (MMPs). MMPs play an important role in solid tumor invasion and migration. Materials and methods The activity and expression of gelatinases (MMP-2 and MMP-9) and collagenases (MMP-1 and MMP-13), protein, and mRNA were detected by gelatin zymography, and RT-PCR. The migratory and invasive capacities of MCF-7 cell lines were measured by the wound scratch migration assay. The preliminary cytotoxicity testing was done by MTT assay and propidium iodide staining. Further the inhibition of inflammatory mediators was also done by quantification of nitrite inflammatory mediators. Results The study showed that PE and its isolated iridoids glycosides PS, KS, and KT exhibited considerable cytotoxic potential in a dose-dependent manner. Further PE, PS, KS, and KT inhibited MCF-7 cell invasion and migration, and decreased MMP-2, 9 and MMP-1, 13 activities. Furthermore, PS, KS, and KT reduced MMPs expression at protein and mRNA levels, and suppression of the inflammatory mediators was also exhibited. Conclusions Our results suggest that PS, KS, and KT may be the valuable anti-invasive drug candidates for cancer therapy by suppressing Collagenases and Gelatinases. PS, KS, and KT showed good results in comparison with PE. PS and KS exhibit almost comparable down regulation while KT exhibited maximum suppression of invasion, migration, and expression of MMPs.

Chloro-bis(2,2-dithio-1,3,2-dioxaphospholane/dioxaphosphorinane)bismuth(III) compounds have been synthesized by the reaction of bismuth trichloride with sodium 2,2-dithio-1,3,2-dioxaphospholane/dioxaphosphorinane in 1:2 molar ratio in benzene solution. Reactions of these chloro-bis(2,2-dithio-1,3,2-dioxaphospholane/dioxaphosphorinane)-bismuth(III) compounds with sodium tetraisopropoxyborate in equimolar ratio in benzene solution yield the corresponding heterobinuclear bismuth derivatives with boron. All compounds were characterized by elemental analyses and molecular weight measurements. Plausible structures are proposed on the basis of IR and 1H, 11B, 13C, and 31P spectroscopic studies. 2-Mercapto-2-thioxo-1,3,2-dioxaphospholanes-/dioxaphosphorinanes and the corresponding chloro-bis(2,2-dithio-1,3,2-dioxaphospholane/dioxaphosphorinane)bismuth (III) compounds show antifungal activities against Fusarium and Trichoderma. Supplemental materials are available for this article. Go to the publisher's o...

Equimolar reactions of Ph n M(OPr i )2 (where M = As and Sb) with Schiff bases [OHC6H4CH=N(R)OH] in benzene solution yield organoarsenic and -antimony derivatives, (where M = As and Sb; n = 1 and 3; R = –CH2CH(CH3)–, –(CH2)3–, –(CH2)2–, and –C(CH3)2CH2–). All these derivatives have been characterized by elemental analyses and molecular weight measurements, and structures have been proposed on the basis of IR, NMR (1H and 13C), and FAB-mass studies. Schiff bases and their corresponding organoantimony derivatives have been screened for antimicrobial activity against Aspergillus flavus (fungus) and Escherichia coli (bacteria).

INTRODUCTION: The cervical vertebrae are seven in number. They are the smallest of the vertebrae and can be identified by the presence of a foramen in each transverse process. The dorsal and ventral roots terminate laterally as dorsal and ventral tubercles. The roots are connected lateral to the foramen by an intertubercular lamella. The vertebral artery which arises from the superoposterior aspect of the first part of the subclavian artery, passes through the foramina in the transverse processes of all of the cervical vertebrae except the seventh. It then curves medially behind the lateral mass of the atlas and enters the cranium through the foramen magnum 1 . The vertebral vein begins in suboccipital venous plexus and descends in foramen transversarium (FT). At the lower end the plexus unites into a single vein, which lies in front of the vertebral artery and terminates into the posterior surface of the first part of Brachiocephalic vein, or lower end of internal jugular vein2. Thus FT transmits the second part of vertebral artery with its accompanying veins and a sympathetic plexus from the lower cervical ganglion. The seventh foramen transmits a vein and a grey ramus from the lower ganglion running up to join the seventh nerve. The ganglion is situated beside the vertebral artery below the level of the seventh costal process, so that its filament to the eighth nerve reaches it directly, but that for the seventh must ascend through the foramen3. MATERIALS AND METHODS: During inspection of 72 cervical vertebrae housed in the Department of Anatomy, Meenakshi Medical College and Research Institute, divided foramen transversarium was noticed in four vertebrae, which were photographed. The length of bony bars and the diameters of the foramina were measured by digital vernier caliper.

Atlas is the first cervical vertebra with a groove for the vertebral artery on the posterior arch. We found an abnormal foramina on the posterior arch. The size of the foramina were measured by sliding caliper. The vertebral artery is vulnerable to compression in its course between foramen transversarium and the foramen magnum during extreme rotation of the head and neck. This situation may be aggravated by the presence of posterior or lateral bridge of the Atlas and result in compromised blood flow. The incidence of the bony ring formed by posterior bridging has been demonstrated in Atlases of various races across the world, which varies between 1.875% to 29.2%. In an examination of twenty eight South Indian Atlases it was found in 10.7% of the cases. The presence of this bony bridging should be taken in to account during a surgical manipulation of the cervical spine.