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Introduction: Karimnagar District has consistently achieved highest rates of no-scalpel vasectomy (NSV) in the past decade when compared to state and national rates. This study was conducted to elucidate the underlying causes for higher acceptance of NSV in the district. Materials and Methods: A community-based, case control study was conducted. Sampling techniques used were purposive and simple random sampling. A semi-structured questionnaire was used to evaluate the socio-demographic, family characteristics, contraceptive history and predictors of contraceptive choice in 116 NSV acceptors and 120 other contraceptive users (OCUs). Postoperative complications and experiences were ascertained in NSV acceptors. Results: Age (χ2 =11.79, P value = 0.008), literacy (χ2 =17.95, P value = 0.03), duration of marriage (χ2 =14.23, P value = 0.008) and number of children (χ2 =10.45, P value = 0.01) were significant for acceptance of NSV. Among the predictors, method suggested by peer/ health worker (OR = 1.5, P value = 0.01), method does not require regular intervention (OR = 1.3, P value = 0.004) and permanence of the method (OR = 1.2, P value = 0.031) were significant. Acceptors were most satisfied with the shorter duration required to return to work and the most common complication was persistent postoperative pain among 12 (10.34%) of the acceptors. Conclusion: Advocating and implementing family planning is of high significance in view of the population growth in India and drawing from the demographic profile, predictors, pool of trainers and experiences in Karimnagar District, a similar achievement of higher rates of this simple procedure with few complications can be replicated.

The green synthesized silver nanoparticles (AgNPs) with the aqueous extract of the leaves of household vegetable, Trigonella foenumgraecum were characterized and tested for their anti-oxidant and anti-bacterial efficacy with sixteen human clinical isolates. The Formation of AgNPs was confirmed with the surface plasmon spectra of the dark brown solution centered at 448 nm. The Particle size calculated with XRD data was 41.23 nm and the SEM size ranged between 52.56 nm and 80.51 nm. The presence of -NH and -OH groups that effectively react and reduce Ag+ ions to Ag0 was evident from the FT-IR spectra. The particles are predominantly spherical in shape and varied from 5 to 80 nm in size. As Suggested from the analysis by SEM and TEM, majority of them fall between 5 nm and 20 nm. A composite solution of AgNPs with polyvinyl alcohol (PVA) was electrospun into films and tested on 8 human clinical isolates including methicillin-resistant Staphylococcus aureus (MRSA). The PVA-AgNP films showed enormous activity against the MRSA prompting further study as wound dressings in the Wistar albino rat model. Although the animal study was abruptly terminated owing to the pandemic-induced lock down, the preliminary study results for 9 days suggest the potential clinical applications of these wound dressings. The synthesized AgNPs with and without PVA demonstrated good anti-oxidant activity and highly significant (P = 0.001) zones of inhibition with eighteen clinical isolates were tested. [ABSTRACT FROM AUTHOR]

Introduction: Karimnagar District has consistently achieved highest rates of no-scalpel vasectomy (NSV) in the past decade when compared to state and national rates. This study was conducted to elucidate the underlying causes for higher acceptance of NSV in the district. Materials and Methods: A community-based, case control study was conducted. Sampling techniques used were purposive and simple random sampling. A semi-structured questionnaire was used to evaluate the socio-demographic, family characteristics, contraceptive history and predictors of contraceptive choice in 116 NSV acceptors and 120 other contraceptive users (OCUs). Postoperative complications and experiences were ascertained in NSV acceptors. Results: Age (χ² =11.79, P value = 0.008), literacy (χ² =17.95, P value = 0.03), duration of marriage (χ² =14.23, P value = 0.008) and number of children (χ² =10.45, P value = 0.01) were significant for acceptance of NSV. Among the predictors, method suggested by peer/ health worker (OR = 1.5, P value = 0.01), method does not require regular intervention (OR = 1.3, P value = 0.004) and permanence of the method (OR = 1.2, P value = 0.031) were significant. Acceptors were most satisfied with the shorter duration required to return to work and the most common complication was persistent postoperative pain among 12 (10.34%) of the acceptors. Conclusion: Advocating and implementing family planning is of high significance in view of the population growth in India and drawing from the demographic profile, predictors, pool of trainers and experiences in Karimnagar District, a similar achievement of higher rates of this simple procedure with few complications can be replicated. [ABSTRACT FROM AUTHOR]

An isocratic, stability-indicating, reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the quantitative determination of doxofylline and terbutaline sulphate, used for the treatment of respiratory problems. The chromatographic separation was achieved on a Zorbax-SB Phenyl 250 x 4.6mm x 5 μm column with the mobile phase consisting of a mixture of 25 mM ammonium acetate (pH 5.0): acetonitrile (85:15 %v/v) at a flow rate of 1.0 ml/min. The eluate was monitored at 274 nm using a PDA detector. Forced degradation studies were performed on the bulk sample of doxofylline and terbutaline sulphate using acid (0.1 N HCI), base (0.1N NaOH), oxidation (10% hydrogen peroxide), photolytic, and thermal degradation conditions. Good resolution was observed between the degradants and analytes. Degradation products resulting from the stress studies did not interfere with the detection of doxofylline and terbutaline sulphate, thus the assay is stability-indicating. The method has the requisite accuracy, selectivity, sensitivity, and precision for the simultaneous estimation of doxofylline and terbutaline sulphate in bulk and pharmaceutical dosage forms. The limit of quantitation and limit of detection were found to be 1.16 ug/ml and 0.38 μg/ml for doxofylline, 2.08 μg/ml and 0.62 μg/ml for terbutaline sulphate, respectively [ABSTRACT FROM AUTHOR]

Elevated levels of reactive oxygen species (ROS) reduce replication fork velocity by causing dissociation of the TIMELESS-TIPIN complex from the replisome. Here, we show that ROS generated by exposure of human cells to the ribonucleotide reductase inhibitor hydroxyurea (HU) promote replication fork reversal in a manner dependent on active transcription and formation of co-transcriptional RNA:DNA hybrids (R-loops). The frequency of R-loop-dependent fork stalling events is also increased after TIMELESS depletion or a partial inhibition of replicative DNA polymerases by aphidicolin, suggesting that this phenomenon is due to a global replication slowdown. In contrast, replication arrest caused by HU-induced depletion of deoxynucleotides does not induce fork reversal but, if allowed to persist, leads to extensive R-loop-independent DNA breakage during S-phase. Our work reveals a link between oxidative stress and transcription-replication interference that causes genomic alterations recurrently found in human cancer., (© 2023. The Author(s).)

Genome integrity must be tightly preserved to ensure cellular survival and to deter the genesis of disease. Endogenous and exogenous stressors that impose threats to genomic stability through DNA damage are counteracted by a tightly regulated DNA damage response (DDR). RNA binding proteins (RBPs) are emerging as regulators and mediators of diverse biological processes. Specifically, RBPs that bind to adenine uridine (AU)-rich elements (AREs) in the 3' untranslated region (UTR) of mRNAs (AU-RBPs) have emerged as key players in regulating the DDR and preserving genome integrity. Here we review eight established AU-RBPs (AUF1, HuR, KHSRP, TIA-1, TIAR, ZFP36, ZFP36L1, ZFP36L2) and their ability to maintain genome integrity through various interactions. We have reviewed canonical roles of AU-RBPs in regulating the fate of mRNA transcripts encoding DDR genes at multiple post-transcriptional levels. We have also attempted to shed light on non-canonical roles of AU-RBPs exploring their post-translational modifications (PTMs) and sub-cellular localization in response to genotoxic stresses by various factors involved in DDR and genome maintenance. Dysfunctional AU-RBPs have been increasingly found to be associated with many human cancers. Further understanding of the roles of AU-RBP S in maintaining genomic integrity may uncover novel therapeutic strategies for cancer.

In recent years, fluorescent sensors have emerged as attractive imaging probes due to their distinct responses toward bio-relevant metal ions. However, the bioimaging application main barrier is the 'turn-off' response toward paramagnetic metal ions such as Cu 2+ under physiological conditions. Herein, we report a new sensor (2-methyl(4-bromo-N-ethylpiperazinyl-1,8-naphthalimido)-4-(1H-phenanthro[9,10-d]imidazole-2-yl) phenol)NPP with multifunctional (Naphthalimide, Piperazine, Phenanthroimidazole) units for fluorescent and colourimetric detection of Cu 2+ in an aqueous medium. Both absorption and fluorescence spectral titration strategies were used to monitor the Cu 2+ -sensing property of NPP. The NPP displays a weak emission at ca. 455 nm, which remarkably enhances (⁓3.2-fold) upon selective binding of Cu 2+ over a range of metal ions, including other paramagnetic metal ions (Mn 2+ , Fe 3+ , Co 2+ ). The stoichiometry, binding constant (K a ) and the LOD (limit of detection) of NPP toward Cu 2+ ions were found to be 1:1, 5.0 (± 0.2) × 10 4  M -1 and 6.5 (± 0.4) × 10 -7  M, respectively. We have also used NPP as a fluorescent probe to detect Cu 2+ in live (human cervical HeLa) cancer cells. The emission intensity of NPP was almost recovered in HeLa cells by incubating 'in situ' the derived Cu 2+ complex (NPP-Cu 2+ ) in the presence of a benchmark chelating agent such as EDTA (ethylenediaminetetraacetate). The fluorescent emission of NPP was reverted significantly in each cycle upon sequencial addition of Cu 2+ and EDTA to the NPP solution. Overall, NPP is a novel, simple, economic and portable sensor that can detect Cu 2+ in biological and environmental scenarios., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation. Here, we show that these DNA transactions are promoted by RECQ5 DNA helicase in a manner dependent on its Ser727 phosphorylation by CDK1. Upon replication stress, RECQ5 associates with CFSs in early mitosis through its physical interaction with MUS81 and promotes MUS81-dependent mitotic DNA synthesis. RECQ5 depletion or mutational inactivation of its ATP-binding site, RAD51-interacting domain, or phosphorylation site causes excessive binding of RAD51 to CFS loci and impairs CFS expression. This leads to defective chromosome segregation and accumulation of CFS-associated DNA damage in G1 cells. Biochemically, RECQ5 alleviates the inhibitory effect of RAD51 on 3'-flap DNA cleavage by MUS81-EME1 through its RAD51 filament disruption activity. These data suggest that RECQ5 removes RAD51 filaments stabilizing stalled replication forks at CFSs and hence facilitates CFS cleavage by MUS81-EME1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A fungus was isolated from the stem cuttings of Taxus celebica, which produced paclitaxel in liquid-grown cultures. The fungus was identified as Fusarium solani based on colony characteristics, morphology of conidia and the 26S rDNA sequence. Paclitaxel was identified by chromatographic and spectroscopic comparison with authentic paclitaxel and its cytotoxic activity towards Jurkat cells in vitro.

Plant ribosome-inactivating proteins (RIPs) are RNA N-glycosidases that inhibit protein synthesis in cells. Abrin, a type II RIP, is an AB type toxin, which is one of the most lethal types of toxin known. The B chain facilitates the entry of the molecule into the cell, whereas the A chain exerts the toxic effect. We have generated hybridomas secreting antibodies of the immunoglobulin G class specific to the recombinant A chain of abrin. One monoclonal antibody, namely, D6F10, rescued cells from abrin toxicity. Importantly, the antibody also protected mice from lethal doses of the toxin. The neutralizing effect of the antibody was shown to be due to interference with abrin attachment to the cell surface.

Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that approximately 200-2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate.

Ribosome inactivating proteins (RIPs) are protein toxins that are of plant or microbial origin that inhibit protein synthesis by inactivating ribosomes. Recent studies suggest that RIPs are also capable of inducing cell death by apoptosis. Though many reports are available on cell death induced by RIPs, the mechanism involved is not well studied. Comparison of pathways of apoptosis and cellular events induced by various RIPs suggests a central role played by mitochondria, probably acting as an integrator of cellular stress and cell death. The purpose of this review is to compare the various apoptotic pathways that may be involved and propose a general pathway in RIP-induced cell death.