Heterocycles in organic synthesis. III A facile synthesis of isoquinolinyl vinyl sulphides

Vinyl sulphides find a substantial application in organic synthesis. The synthetic utility of heter cyclic vinyl sulphides due to the ease in extension of heterocyclic ring should be more versatile, Here, we report the synthesis of isoquinolinyl vinyl sulphides from dihydrothiazolo [2, 3-a-] isoquinolinium cations, depicting another use of heterocycles in organic synthesis

The hnRNP A1 homolog Hrp36 is essential for normal development, female fecundity, omega speckle formation and stress tolerance in Drosophila melanogaster

Hrp36/Hrb87F is one of the most abundant and well-characterized hnRNP A homolog in Drosophila and is shown to have roles in regulation of alternative splicing, heterochromatin formation, neurodegeneration, etc. Yet, hrp36 null individuals were reported to be viable and without any apparent phenotype, presumably because of overlapping functions provided by Hrp38 and related proteins. Here we show that loss of both copies of hrp36 gene slows down development with significant reduction in adult life span, decreased female fecundity and high sensitivity to starvation and thermal stresses. In the absence of Hrp36, the nucleoplasmic omega speckles are nearly completely disrupted. The levels of nuclear matrix protein Megator and the chromatin remodeller ISWI are significantly elevated in principal cells of larval Malpighian tubules, which also display additional endoreplication cycles and good polytene chromosomes. We suggest that besides the non-coding hsr omega-n transcripts, the Hrp36 protein is also a core constituent of omega speckles. The heat-shock-induced association of other hnRNPs at the hsr omega locus is affected in hrp36 null cells, which may be one of the reasons for their high sensitivity to cell stress. Therefore, in spite of the functional redundancy provided by Hrp38, Hrp36 is essential for normal development and for survival under conditions of stress

Water Quality and Pollution Status of Lararpur Reservoir with Special Reference to Bacterial Contamination

Laharpur dam was constructed in the southwest of Bhopal city, M.P., India with an objective to store water for irrigational purpose. At the time of planning and construction of the reservoir it was in the outskirts of township but now, with the expansion of the city the reservoir has come well within the settlement. The developmental activities and occupancy in the area is exerting pressure on the water body. Surface water in urban water bodies almost always contains some degree of contamination. This is due to exposure to animals, humans, aquatic life, etc. In addition to this, variety of other human activities resulted in increasing the bacterial concentration of reservoir. Many of these bacteria are pathogenic and spread diseases like typhoid, paratyphoid, gastroenteritis etc. Inflow of sewage in the surface water may play an important role in the transmission of pathogenic agents discharged through feces. Some pathogenic bacteria like Actinomyces sp., Aerobacter aerogenes, A. cloacae, Micrococcus sp., Salmonella sp., Staphylococcus aureus, Bacillussp, and Shigella species indicate the higher level of fecal contamination of water. This untreated water poses a serious threat to the health of consumers and therefore, calls for urgent intervention by government.
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Anti-tuberculosis drug induced hepatotoxicity: a study from Himalayan region

Background: Tuberculosis (TB) is the infection of global health concern. The management of TB is a 6-month course of anti-TB drugs. Compliance is crucial for curing TB. Adverse effects often affect the compliance negatively. One of the adverse effects affecting TB treatment outcome is anti-TB drug induced hepatotoxicity (DIH). Therefore, the purpose of this study was to assess the incidence of anti-TB DIH and its associated factors among newly diagnosed TB patients.Methods: A single centre prospective study was conducted from January-December 2020. All patients who were newly-diagnosed for TB, started anti-TB medication and diagnosed with drug-induced liver injury during anti-tubercular treatment included in the study.Results: Total of four hundred and ninety-two (492) TB patients taking anti-TB drugs were involved in this study with male predominance and maximum in the age group of 30-45 years. Smear-positive pulmonary TB accounted for 66.9% of all cases. During the study period, 9.3% TB patients developed anti-TB DIH. Among the cases of anti-TB DIH, female patients account for 52%. Patients with extra-pulmonary TB (n=23), low BMI (n=16), alcohol consumption (n=21) had developed anti-TB DIH. The time interval from the initiation of treatment to the onset of hepatotoxicity was 16-45 days.Conclusion: The chances of hepatotoxicity among TB patients taking anti-TB drugs are always there. Thus, it is necessary to monitor liver function in patients receiving anti-TB drugs routinely

Pojava bruceloze na farmi mliječnih krava i mogućnost njenog prijenosa na ljude u Himachal Pradesh, Indija.

Brucellosis is an important disease of livestock species and wild animals, as well as a significant health hazard in contact human beings, causing a variety of reproductive disorders in cattle under intensive farming. This report is about an outbreak of brucellosis in an organized dairy farm, leading to abortions, retained placenta and stillbirths in cows. The Brucella abortus biotype-I was isolated from placentas, uterine discharges, vaginal swabs and foetal stomach contents collected from infected animals. The serological study, employing rose bengal plate test (RBPT) and serum agglutination test (SAT), revealed involvement of both B. abortus and B. melitensis in all affected cows. Seropositive cases for B. melitensis were also found among 10% of contact animal handlers, having a history of human brucellosis-like symptoms. The isolates were found sensitive to streptomycin, chlortetracycline, ciprofloxacin, ampicillin, tetracycline and gentamicin. The haematological study revealed severe monocytosis averaging 33% and lymphocytosis averaging 32.8% in all infected animals.Bruceloza je važna bolest domaćih i divljih životinja, koja predstavlja prijetnju za zdravlje ljudi u dodiru s inficiranim životinjama. Očituje se različitim reprodukcijskim poremećajima. Opisana je pojava bruceloze na farmi mliječnih krava, gdje je uzrokovala pobačaje, zaostajanje posteljice i mrtvorođenja. Brucella abortus biotip I bila je izdvojena iz posteljica, materničnih iscjedaka i vaginalnih obrisaka te sadržaja sirišta pobačenih plodova. Serološkim pretragama pomoću aglutinacijskog i serum aglutinacijskog testa u zaraženih životinja bile su dokazane vrste B. abortus i B. melitensis. Serološki pozitivni nalazi za B. melitensis dokazani su u 10% osoba koje su bile u dodiru sa životinjama, a u anamnezi je bilo ustanovljeno da su imale kliničke znakove slične brucelozi. Izdvojene brucele bile su osjetljive na streptomicin, klortetraciklin, ciprofloksacin, ampicilin, tetraciklin i gentamicin. Hematološkom pretragom dokazana je monocitoza u 33% te limfocitozu u 32,8% svih inficiranih životinja

A triphenylethylene nonsteroidal SERM attenuates cervical cancer growth

Selective estrogen receptor modulator drug molecules of triphenylethylene family have gained considerable attention as anti-cancer agents. Despite recent advances in screening and development of HPV vaccines, cervical cancer remains one of the deadliest malignancies as advanced stage metastatic disease is mostly untreatable, thus warrants newer therapeutic strategies. Ormeloxifene (ORM) is a well-known SERM of triphenylethylene family that has been approved for human use, thus represents an ideal molecule for repurposing. In this study, we for the first time have demonstrated the anti-cancerous properties of ormeloxifene in cervical cancer. Ormeloxifene efficiently attenuated tumorigenic and metastatic properties of cervical cancer cells via arresting cell cycle at G1-S transition, inducing apoptosis, decreasing PI3K and Akt phosphorylation, mitochondrial membrane potential, and modulating G1-S transition related proteins (p21, cyclin E and Cdk2). Moreover, ORM repressed the expression of HPV E6/ E7 oncoproteins and restored the expression of their downstream target tumor suppressor proteins (p53, Rb and PTPN 13). As a result, ormeloxifene induces radio-sensitization in cervical cancer cells and caused potent tumor growth inhibition in orthotopic mouse model. Taken together, ormeloxifene represents an alternative therapeutic modality for cervical cancer which may have rapid clinical translation as it is already proven safe for human use

Emerging Roles and Potential Applications of Non-Coding RNAs in Cervical Cancer

Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome’s composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemoresistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC.We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC.We also address contemporary technologies such as antisense oligonucleotides, CRISPR–Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC

Smoking and Drinking Activates NF-κB /IL-6 Axis to Promote Inflammation During Cervical Carcinogenesis

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated the molecular mechanisms involved in the interplay of smoking and/or drinking with HPV infectivity and defined a systematic therapeutic approach for their attenuation in cervical cancer. Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in cell proliferation, clonogenicity, biophysical properties, cell migration, and invasion. Expression of HPV16 E6/E7, NF-κB, cytokines, cell cycle, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay and confocal microscopy. Results: The exposure of cervical cancer cells to B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers; it also enhanced cellular clonogenicity, migration, and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGFA. These molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by Cur/PLGA-Cur. Conclusion: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. However, these events were determined to be attenuated by treatment with Cur/PLGA-Cur treatment, implying its role in cervical cancer prevention/treatment

Interaction of oxygen (O+7) ion beam on polyaniline thin films

High-energy ion beam irradiation of the polymers is a good technique to modify the properties such as electrical conductivity, structural behaviour and mechanial properties. Polyaniline thin films doped with hydrochloric acid (HCl) were prepared by oxidation of ammonium persulphate. The effect of Swift Heavy Ions irradiation on the electrical and structural properties of polyaniline has been measured in this study. Polyaniline films were irradiated by oxygen ions (energy 80 MeV, charge state O+7) with fluence varying from 1 × 1010 to 3 × 1012 ions/cm2. The studies on electrical and structural properties of the irradiated polymers were investigated by measuring V-I using four probe set-up and X-ray diffraction (XRD) using Bruker AXS, X-ray powder diffractometer. V-I measurements shows an increase in the conductivity of the film, XRD pattern of the polymer shows that the crystallinity improved after the irradiation with Swift Heavy Ions (SHI), which could be attributed to cross linking mechanism.Subhash Chandra1*, S Annapoorni2, R G Sonkawade3, P K Kulriya3 Fouran Singh3, D K Avasthi3, J M S Rana1 and R C Ramola1 1Department of Physics, H N B Garhwal University, Badshahi Thaul Campus, Tehri Garhwal-249 199, Uttarakhand, India 2Department of Physics and Astrophysics, University of Delhi, Delhi-110 007, India 3Inter University Accelerator Center, Aruna Asaf Ali Marg, New Delhi-110 067, India E-mail : [email protected] of Physics, H N B Garhwal University, Badshahi Thaul Campus, Tehri Garhwal-249 199, Uttarakhand, India Department of Physics and Astrophysics, University of Delhi, Delhi-110 007, India Inter University Accelerator Center, Aruna Asaf Ali Marg, New Delhi-110 067, Indi