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XIST (X-inactive specific transcript) long noncoding RNA (lncRNA) is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both X chromosomes in human female preimplantation embryos without triggering X chromosome silencing. The XACT (X-active coating transcript) lncRNA coaccumulates with XIST on active X chromosomes and may antagonize XIST function. Here, we used human embryonic stem cells in a naive state of pluripotency to assess the function of XIST and XACT in shaping the X chromosome chromatin and transcriptional landscapes during preimplantation development. We show that XIST triggers the deposition of polycomb-mediated repressive histone modifications and dampens the transcription of most X-linked genes in a SPEN-dependent manner, while XACT deficiency does not significantly affect XIST activity or X-linked gene expression. Our study demonstrates that XIST is functional before XCI, confirms the existence of a transient process of X chromosome dosage compensation and reveals that XCI and dampening rely on the same set of factors., (© 2024. The Author(s).)

Background  The keystone design perforator island flap (KDPIF) is unique among local flaps because of its high potential for adaptation. We describe our experience with the use of the keystone flap for the reconstruction of a variety of defects in different regions of the body concerning its versatility, surgical outcomes, complications, postoperative pain, operative time, and esthetic outcomes. Methods  A prospective observational study was conducted at our institute from June 2021 to June 2023 where the use of KDPIFs in resurfacing soft tissue defects of different etiopathogenesis was evaluated and the data were analyzed. Results  Forty-four patients were included in the study with soft tissue defects of various etiologies and at different locations. The largest flap raised was 18 × 10 cm and the smallest was 4 × 2 cm. The average intraoperative time for completion of the procedure was 74.86 minutes (range: 45-120 minutes). The success rate of flap survivability was 95.45% with two patients having total flap loss necessitating another reconstructive option. Partial flap dehiscence which healed secondarily was observed in two patients. Postoperative pain showed a significant fall of 83.7% from baseline and 82.9% of cases were extremely satisfied with the esthetic outcome. Conclusion  The keystone flap is a valuable reconstructive tool in the armamentarium of a plastic surgeon. It is technically reproducible, suitable to be done in resource-limited settings, and provides contiguous tissue with good vascularity and fewer complications., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The advent of novel 2D and 3D models for human development, including trophoblast stem cells and blastoids, has expanded opportunities for investigating early developmental events, gradually illuminating the enigmatic realm of human development. While these innovations have ushered in new prospects, it has become essential to establish well-defined benchmarks for the cell sources of these models. We aimed to propose a comprehensive characterization of pluripotent and trophoblastic stem cell models by employing a combination of transcriptomic, proteomic, epigenetic, and metabolic approaches. Our findings reveal that extended pluripotent stem cells share many characteristics with primed pluripotent stem cells, with the exception of metabolic activity. Furthermore, our research demonstrates that DNA hypomethylation and high metabolic activity define trophoblast stem cells. These results underscore the necessity of considering multiple hallmarks of pluripotency rather than relying on a single criterion. Multiplying hallmarks alleviate stage-matching bias., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With a recent amendment, India joined other countries that have removed the legislative barrier toward the use of human-relevant methods in drug development. Here, global stakeholders weigh in on the urgent need to globally harmonize the guidelines toward the standardization of microphysiological systems. We discuss a possible framework for establishing scientific confidence and regulatory approval of these methods., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Berberis aristata (BA) has been described in Ayurveda in formulations for treating conditions related to the buccal cavity, including tumours and inflammation. Oral cancer (OC) is a major global health problem with high rates of recurrence and metastasis. Natural product based therapies are being explored as safer therapeutic strategies for OC., Aim of the Study: Evaluating the potential of standardized BA extract loaded buccal spray formulation in OC., Material and Methods: BA stem bark extract was prepared using sonication and standardized with respect to Berberine. The standardized extract was characterized and formulated as a buccal spray (SBAE-BS) using hydroxyl propyl methyl cellulose K15M, polyethylglycol 400, Miglyol®812N and ethanol. The SBAE-BS was characterized and evaluated in vitro in KB cell line and in vivo in OC hamster model., Results: The SBAE-BS had pH, viscosity, mucoadhesive strength and BBR content corresponding to 6.8, 25.9 cP, 345 dyne/cm2 and 0.6 mg/mL respectively. In vitro cytotoxicity of SBAE-BS was comparable to 5 fluorouracil (5FU). In hamsters, SBAE-BS treatment lead to tumour regression (p = 0.0345), improved body weights (p < 0.0001), no organ toxicity, downregulation of inflammatory mediators and improved survival outcomes as compared to standard systemic 5FU., Conclusion: Thus, SBAE-BS showed cytotoxic and chemo-protective effects in the OC hamster model, evidencing its ethnopharmacological use and demonstrating translational potential to be developed as therapy for OC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The past decade has seen expeditious developments in our ability to grow and maintain a variety of human cells and tissues, with properties closely mimicking those in the human body. Prominent researchers and entrepreneurs from all over the world assembled in Hyderabad, India to discuss developments in this field that have not only aided fundamental understanding of organ development and disease processes but have served as good physiological models for toxicity testing and drug development. The speakers presented ingenious, cutting-edge technology and forward-thinking ideas. This report presents the salient aspects of their discussions, highlights the importance of identifying unmet needs, and discusses setting of standards that will help regulatory approvals as we move into a new era, with nominal animal use in research and effective drug discovery., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Background: In India, for the treatment of cold, fever and inflammation, people consume herbal remedies containing Andrographis paniculata Nees (APE) as main ingredient, along with NSAIDs. So the purpose of this study is to investigate the effect of APE and pure andrographolide (AN) on the pharmacokinetic of with aceclofenac (ACF) and celecoxib (CXB) after oral co-administration in wistar rats. After co-administration of APE (equivalent to 20 mg/kg of AN) and AN (20 mg/kg) with ACF (5 mg/kg) and CXB (5 mg/kg) in rats, orally, drug concentrations in plasma were determined using HPLC method. Non-compartment model was used to calculate pharmacokinetic parameters like Cmax, Tmax, t 1/2, MRT, Vd, CL, and AUC., Results: Co-administration of ACF and CXB with APE and pure AN altered the systemic exposure level of each compound in vivo. The Cmax, Tmax, MRT of CXB were increased whereas Vd and Cl of CXB were decreased significantly after co-administration of CXB with APE. Whereas co-administration of CXB with AN significantly decreased Vd, CL, and MRT of CXB. The concentration of ACF was increased significantly in co-administered groups with pure AN and APE. The AUC0-∞, AUMC0-∞, MRT, Vd and t 1/2 of ACF were also significantly decreased in co-administered groups, hence CL of ACF was increased significantly., Conclusion: This study concludes that APE and pure AN have effect on pharmacokinetic of CXB and ACF in rat. Not only patients but medical practitioners using Andrographis paniculata should have awareness regarding probable herb-drug interactions with ACF and CXB., Competing Interests: Consent for publicationThe authors declare no conflict of interest.Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

Skeletal muscle mass responds rapidly to growth stimuli, precipitating hypertrophies (increased protein synthesis) and hyperplasia (activation of the myogenic program). For ages, muscle degeneration has been attributed to changes in the intracellular myofiber pathways. These pathways are tightly regulated by hormones and lymphokines that ultimately pave the way to decreased anabolism and accelerated protein breakdown. Despite the lacunae in our understanding of specific pathways, growing bodies of evidence suggest that the changes in the myogenic/regenerative program are the major contributing factor in the development and progression of muscle wasting. In addition, inflammation plays a key role in the pathophysiology of diseases linked to the failure of skeletal muscles. Chronic inflammation with elevated levels of inflammatory mediators has been observed in a spectrum of diseases, such as inflammatory myopathies and chronic obstructive pulmonary disease (COPD). Although the pathophysiology of these diseases varies greatly, they all demonstrate sarcopenia and dysregulated skeletal muscle physiology as common symptoms. Medicinal plants harbor potential novel chemical moieties for a plenitude of illnesses, and inflammation is no exception. However, despite the vast number of potential antiinflammatory compounds found in plant extracts and isolated components, the research on medicinal plants is highly daunting. This review aims to explore the various phytoconstituents employed in the treatment of inflammatory responses in skeletal muscles, while providing an in-depth molecular insight into the latter., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Dipanjan Karati et al.)

Introduction A ventral hernia is a common problem in the population. Many patients with umbilical/epigastric hernia often present with diastasis recti (DR) too. Diastasis recti is the thinning of the linea alba with an abnormal increase in the distance between the recti without a concomitant fascial defect. The presence of diastasis recti complicates the repair of the existing umbilical/epigastric hernia. Repair of only the umbilical/epigastric hernia in the presence of DR results in incomplete repair and predisposes to recurrence. There are various options available for the repair of umbilical hernia with diastasis recti. Open hernia repairs often have unsatisfactory cosmetic outcomes and, furthermore, involve complications frequently associated with large incisions such as surgical site occurrences (SSO), pain, dermal flap necrosis, and delayed postoperative recovery, to name a few. The era of minimal access surgery leaves us with a vast array of creative solutions to the same. Laparoscopic onlay repair has been given various names in literature, e.g., minimally invasive linea alba reconstruction (MILAR), pre-aponeurotic endoscopic repair (REPA), endoscopic linea alba reconstruction (ELAR), subcutaneous onlay laparoscopic approach (SCOLA), and totally endoscopic assisted linea alba reconstruction (TESLAR), with similar principles for all the procedures. The average rate of seroma formation in these procedures varies from 5% to 40%. SCOLA has been used in our study, with an added modification of the operating port and limiting the extent of lateral dissection with the aid of spinal needles, resulting in restrained dissection and creation of smaller lipocutaneous flaps, leading to reduced incidence of seroma formation. Methods Patients with symptomatic primary ventral hernia with concomitant diastasis recti were enrolled in the participating center from the period of May 2020 to December 2021. Thirty patients were enrolled for this prospective study. The patients underwent subcutaneous laparoscopic onlay repair of midline ventral hernia with diastasis recti, with plication of the defect and onlay placement of a polypropylene mesh. Results Six point sixty-six percent (6.66%) of the patients developed seroma and SSO. The incidence is congruent with the results available in current literature. None of the patients had necrosis of umbilical skin. There were no recurrences at the three months follow-up. Conclusion Our modification of SCOLA is an ergonomically favorable procedure and has comparable outcomes to other approaches, with minimal complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Shinde et al.)

Background: Sequencing technologies are prone to errors, making error correction (EC) necessary for downstream applications. EC tools need to be manually configured for optimal performance. We find that the optimal parameters (e.g., k-mer size) are both tool- and dataset-dependent. Moreover, evaluating the performance (i.e., Alignment-rate or Gain) of a given tool usually relies on a reference genome, but quality reference genomes are not always available. We introduce Lerna for the automated configuration of k-mer-based EC tools. Lerna first creates a language model (LM) of the uncorrected genomic reads, and then, based on this LM, calculates a metric called the perplexity metric to evaluate the corrected reads for different parameter choices. Next, it finds the one that produces the highest alignment rate without using a reference genome. The fundamental intuition of our approach is that the perplexity metric is inversely correlated with the quality of the assembly after error correction. Therefore, Lerna leverages the perplexity metric for automated tuning of k-mer sizes without needing a reference genome., Results: First, we show that the best k-mer value can vary for different datasets, even for the same EC tool. This motivates our design that automates k-mer size selection without using a reference genome. Second, we show the gains of our LM using its component attention-based transformers. We show the model's estimation of the perplexity metric before and after error correction. The lower the perplexity after correction, the better the k-mer size. We also show that the alignment rate and assembly quality computed for the corrected reads are strongly negatively correlated with the perplexity, enabling the automated selection of k-mer values for better error correction, and hence, improved assembly quality. We validate our approach on both short and long reads. Additionally, we show that our attention-based models have significant runtime improvement for the entire pipeline-18[Formula: see text] faster than previous works, due to parallelizing the attention mechanism and the use of JIT compilation for GPU inferencing., Conclusion: Lerna improves de novo genome assembly by optimizing EC tools. Our code is made available in a public repository at: https://github.com/icanforce/lerna-genomics ., (© 2021. The Author(s).)

X chromosome activity is a defining attribute of naive pluripotency, with naive pluripotency being a rare context in which both X chromosomes of females are active. RNA-fluorescence in situ hybridization (RNA-FISH) is a powerful tool to determine the transcriptional status of specific genes with allelic and single-cell resolution and has been widely used in the context of X chromosome inactivation, the process ensuring dosage compensation for X-linked genes between sexes in mammals. RNA-FISH using genomic or intronic probes allows the detection of newly synthesized transcripts at the site of transcription. This technique is invaluable for appreciating the putative heterogeneity in the expression profiles within cell populations. RNA-FISH has the added advantage of allowing the visualization of gene transcription in a spatial perspective. Here, we provide a detailed protocol describing the application of RNA-FISH to detect nascent X-linked transcripts in female naive human embryonic stem cells to assess their X chromosome status, along with another complementary technique, DNA-FISH., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To develop and validate bioanalytical RP-HPLC method to evaluate pharmacokinetics and tissue distribution pattern of momordicinin (MRN)., Significance: MRN is one of the major cucurbitane triterpenoid found in Momordica charantia Linn (MC). However, MRN has not been explored for its pharmacokinetic profile, tissue distribution, and stability in order to establish it as an antidiabetic agent., Methods: In 28 days pharmacokinetic study, 54 diabetic male wistar rats were divided into three different groups and administered with 25, 50, and 100 mg/kg MRN orally. The blood samples were collected at 1, 7, 14, 21, and 28th day of the treatment and plasma quantification of MRN was done by validated RP-HPLC method. The rats were sacrificed at end of the study for tissue distribution., Results: The developed method was successfully applied to investigate pharmacokinetic profile of MRN. In pharmacokinetic analysis, the C max for 25, 50, and 100 mg/kg was found to be 8.412, 10.443, and 11.829 µg/mL respectively suggesting the dose dependent activity. The maximum plasma concentration was achieved at 2 h for all doses. MRN showed major distribution in liver followed by kidney, spleen, and pancreas., Conclusion: The newly developed and validated method was used to assay MRN in plasma as well as in tissues to evaluate pharmacokinetics of the drug for the first time. Undoubtedly, these findings can be taken into consideration while concluding its therapeutic effects after oral administration.

The dry powder of MC fruits was extracted by maceration, ultrasonication, liquid-liquid partition and soxhlation. The in vitro antidiabetic and antioxidant assays were used to screen extracts and fractions. Refluxed and liquid partitioned extracts were fractionated using petroleum ether and ethyl acetate and purified with the help of preparative HPLC to give 2 phytoconstituents M1 and M2 respectively. Compound M1 (1) was identified as charantin and Compound M2 (2) was identified as momordicinin using spectral studies. Momordicinin showed potent α-amylase inhibitory activity with IC 50 15.86μg/ml which was reported for the first time.

Background: Honey bee propolis is one of the natural products reported in various traditional systems of medicines, including Ayurveda. Caffeic acid phenethyl ester (CAPE) is an active constituent of propolis which is well known for its anticancer potential. The therapeutic effects of CAPE are restricted owing to its less aqueous solubility and low bioavailability., Objective: In this study CAPE loaded folic acid conjugated nanoparticle system (CLFPN) was investigated to enhance solubility, achieve sustained drug release, and improved cytotoxicity of CAPE Methods: Formulation development, characterization, and optimization were carried out by the design of experiment approach. In vitro and in vivo cytotoxicity study was carried out for optimized formulations., Results: Developed nanoparticles showed particle size and encapsulation efficiency of 170 ± 2-195 ± 3 nm and 75.66 ± 1.52-78.80 ± 1.25%, respectively. Optimized formulation CLFPN showed sustained drug release over a period of 42 h. GI50 concentration was decreased by 46.09% for formulation compared to CAPE in MCF-7 cells, indicating the targeting effect of CLFPN. An improved in vitro cytotoxic effect was reflected in the in vivo Daltons Ascites Lymphoma model by reducing tumor cell count., Conclusion: The desired nanoparticle characteristic with improved in vivo and in vitro cytotoxicity was shown by the developed formulation. Thus it can be further investigated for biomedical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Pregnancy is a stress test of maternal thyroid function. The prevalence of thyroid dysfunction in pregnant women is high. Subclinical hypothyroidism occurs in 10% of all pregnancies. Effects of hypothyroidism in pregnancy are anemia, low birth weight and mental retardation in neonate. This study is aimed to evaluate maternal and fetal outcomes in pregnant women with deranged thyroid profile. The relevance of this study is to document the association of hypothyroidism and its adverse effects on mother and fetus., Methods: This prospective observational study was carried out at R.D. Gardi Medical College, Ujjain, India. Subjects of this study were 198 antenatal women in third trimester with singleton pregnancy admitted in the obstetric ward, and informed consent was obtained. Women were chosen irrespective of age, parity, residence and socioeconomic status. Women with multiple pregnancy, a known case of thyroid disorder, or any pre-existing medical disorder were excluded. Routine hematological parameters and estimation of T3, T4 and TSH was conducted. Patients with deranged thyroid profile were subsequently assessed for maternal and fetal complications. History of infertility, family history of thyroid disease, menstrual pattern, recurrent abortion, hemoglobin level and fetal outcome were the main study variables. Data was analysed in SPSS software for statistical co-relation., Results: Prevalence of thyroid disorder is 11%; with subclinical hypothyroidism, overt hypothyroidism and subclinical hyperthyroidism occurring in 5.6, 3.5 and 1.5% of subjects respectively. In women with subclinical and overt hypothyroidism, anemia was present in 26.3% being significantly associated with hypothyroidism (p = 0.008). With respect to fetal outcome, LBW 31.6% (p = 0.001), NICU admission 42.1%, (p = 0.000) and low APGAR Score (21.1%, p = 0.042) were statistically associated with hypothyroidism. Risk of anemia, Low Birth weight, NICU admissions, and low APGAR score was 4.8, 6.3, 0.14 and 3.64 times higher respectively in women with hypothyroidism than in women who are euthyroid., Conclusion: Prevalence of subclinical hypothyroidism is 5.6% in 3rd trimester of pregnancy. Anemia, pre-eclampsia, high caesarean rates and neonatal morbidities is significantly associated with hypothyroidism.

Targeted drug delivery across the blood-brain barrier is an extremely challenging quest in the fight with fatal brain ailments, with the major hurdles being short circulation time, reticuloendothelial system (RES) uptake, and excretion of nanocarriers. PEGylation has emerged as a boon for targeted drug delivery to the brain. It is well established that PEGylation can increase the circulation time of nanocarriers by avoiding RES uptake, which is indispensable for increasing the brain's uptake of nanocarriers. PEGylation also acts as a linker for ligand molecules to achieve active targeting to the brain. Using PEGylation, novel approaches are being investigated to facilitate ligand-receptor interactions at the brain endothelium to ease the entry of therapeutic drugs into the brain. In addition, PEGylation made it simpler to assess the brain tissue for delivering diagnostic molecules and theranostic nanocarriers. The potential of PEGylated nanocarriers is being investigated vastly to boost the therapeutic effect several fold in the treatment of brain diseases. This review sheds light on the contribution of PEGylated nanocarriers, especially liposomes, polymeric nanoparticles, and dendrimers for brain-specific delivery of bioactives., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Doubling of C-section rates from year 2000 to 2015 globally was declared an eye-opener on October 13, 2018, in FIGO World Congress. Rapid increase in rates without clear evidence of concomitant decrease in maternal or neonatal morbidity or mortality raises significant concern that cesarean delivery is overused. This review addresses issues related to exponentially rising rates, reasons for it, and strategies to reduce. Previous cesarean delivery has main contribution to rising rates as per evidence from the literature search in last 5 years. Focus on optimizing indications of primary C-section resulted in making us rethink modifiable indications like labor dystocia, indeterminate fetal heart rate tracing, suspected fetal macrosomia, malposition, risk-adapted obstetrics, litigation fears, on demand cesarean in literate women and overuse of labor induction. Use of uniform classification system (Robson/WHO classification) with recommendations of WHO, FIGO and annual audits with cloud-based anonymous registry will streamline decisions for cesarean in nullipara and help to control the situation., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Federation of Obstetric & Gynecological Societies of India 2019.)

Remarkable advancements in high-throughput gene sequencing technologies have led to an exponential growth in the number of sequenced genomes. However, unavailability of highly parallel and scalable de novo assembly algorithms have hindered biologists attempting to swiftly assemble high-quality complex genomes. Popular de Bruijn graph assemblers, such as IDBA-UD, generate high-quality assemblies by iterating over a set of k-values used in the construction of de Bruijn graphs (DBG). However, this process of sequentially iterating from small to large k-values slows down the process of assembly. In this paper, we propose ScalaDBG, which metamorphoses this sequential process, building DBGs for each distinct k-value in parallel. We develop an innovative mechanism to "patch" a higher k-valued graph with contigs generated from a lower k-valued graph. Moreover, ScalaDBG leverages multi-level parallelism, by both scaling up on all cores of a node, and scaling out to multiple nodes simultaneously. We demonstrate that ScalaDBG completes assembling the genome faster than IDBA-UD, but with similar accuracy on a variety of datasets (6.8X faster for one of the most complex genome in our dataset).

Chrysin (CH), a phytoconstituent has numerous pharmacological activities including anticancer activity. However, CH suffers from a drawback of poor aqueous solubility and in turn poor bioavailability limiting its clinical utility. In this work CH loaded folate-conjugated pluronic PF127-pluronic F68 mixed micelles were prepared with an objective to augment oral bioavailability and cytotoxicity of CH in human breast cancer cell line MCF-7 by active targeting mechanism. Folate-conjugated PF127 was synthesized and used for preparation of CH-MM. Optimized batch (using factorial design) of CH-MM was characterized by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), atomic force microscopy (AFM), in vitro CH release, in vivo study, and in vitro cell line study. FTIR study suggested encapsulation of CH into the micelle core. CH-MM showed controlled release of CH releasing higher amount (2.5 fold) in 24 h when compared to CH alone (A-CH). Further significant increase in C max (2 fold) and AUC 0-∞ (3 fold) for CH-MM when compared to A-CH suggested significant improvement in oral bioavailability of CH. Additionally, CH-MM showed 5 fold reduction in GI 50 value of CH when tested in MCF-7 cells reducing GI 50 value of CH significantly. CH-MM can serve as a platform carrier system for active targeting of BCS class II molecules with potential anticancer activity.

Background: Propolis from apiculture is known for wide range of medicinal properties owing to its vast chemical constituents including polyphenols, flavonoids and anticancer agent Caffeic acid phenethyl ester (CAPE)., Objectives: The objective of the study was to extract and standardize Indian propolis (IP) with respect to selected markers by newly developed High performance liquid chromatography (HPLC) method, to evaluate in vitro and in vivo anticancer activity and biosafety of Indian propolis., Materials and Methods: IP was extracted, optimized and standardized using a newly developed and validated HPLC method for simultaneous estimation of caffeic acid, apigenin, quercetin and CAPE. The standardised ethanolic extract of IP (EEIP) was screened for in vitro cytotoxicity using sulforhodamine B (SRB) assay, in vivo anti-carcinogenic effect against Dalton's Lymphoma ascites (DLA) cells, hemolytic effect and pesticide analysis., Results: The EEIP was found to contain more amount of total flavonoids (23.61 ± 0.0452 mg equivalent of quercetin/g), total polyphenolics (34.82 ± 0.0785 mg equivalent of gallic acid/g) and all selected markers except caffeic acid compared to all other extracts. EEIP showed better anti-cancer potential than CAPE on MCF-7 and HT-29 cell line and significant (p < 0.01) in vivo anti-carcinogenic effects against DLA in comparison with 5-fluorouracil. EEIP was found to be non-hemolytic., Conclusion: From in vitro cytotoxicity, in vivo anti-carcinogenicity and biosafety studies it can be concluded that the standardized EEIP is safe and can be considered for further development as a biomedicine., (Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

Piperine has been widely used as a bioenhancer. Simvastatin belongs to a group of medicines known as statins. It acts by inhibiting HMG CoA reductase and acts primarily as a hypolipidemic agent. In this study some derivatives of Piperine were synthesized. They were studied for their bioenhencing effect (10 mg kg -1 ) and this effect was compared with that of Piperine. The pharmacokinectic profile of Simvastatin alone and in combination with Piperine and Piperine derivatives were investigated by validated HPLC method as per USFDA guidelines. It was seen that the two synthesized derivatives of Piperine significantly improved the bioavailability of Simvastatin in Wistar rats. The 5-(benzo) [1,3]dioxol-5-yl)-N-(pyridin-4-yl)penta-2,4-dienamide was better amongst the synthesized in increasing the bioavailability of Simvastatin in Wistar rat.

Candida albicans, a human pathogen, carries an expanded family of Zn(II)2Cys6 transcription factors. A CTG clade-specific protein Zcf32 and its closely related protein Upc2, a well-conserved transcription factor across the various fungal species, belong to this family of proteins. Unlike Upc2, Zcf32 is poorly studied in C. albicans. Here, we examined roles played by these two related transcription factors in biofilm development and virulence of C. albicans. Our data show that the null mutants of each of Zcf32 or Upc2 form better biofilms than the wild-type suggesting that both of them negatively regulate the biofilm development. While acting as negative regulators of biofilm formation, these two transcription factors target a different set of biofilm genes. A mouse model of candidiasis reveals that zcf32/zcf32 was hypervirulent, while upc2/upc2 shows compromised virulence compared to the wild-type. Notably, the absence of Zcf32 enhances detrimental inflammation brought about by TNFα, IFNβ and IFNγ. upc2/upc2 failed to generate a similar feedback, instead demonstrated an elevated anti-inflammatory (IL4 and IL10) host response. Taking together, we show how a recently evolved transcription factor Zcf32 retained functional resemblance with a more ubiquitous member Upc2 but also functionally diverged from the latter in the regulation of biofilm development and virulence of the pathogen.

Tissue repair is a complex process that necessitates an interplay of cellular processes, now known to be dictated by epigenetics. Intriguingly, macrophages are testimony to a large repertoire of evolving functions in this process. We identified a role for BMP signaling in regulating macrophage responses to Candida albicans infection during wound repair in a murine model. In this study, the RNA binding protein, AU-rich element-binding factor 1, was posttranslationally destabilized to bring about ubiquitin ligase, NEDD4-directed activation of BMP signaling. Concomitantly, PI3K/PKCδ mobilized the rapid phosphorylation of BMP-responsive Smad1/5/8. Activated BMP pathway orchestrated the elevated recruitment of EZH2 at promoters of genes assisting timely wound closure. In vivo, the repressive H3K27 trimethylation was observed to persist, accompanied by a robust upregulation of BMP pathway upon infection with C. albicans, culminating in delayed wound healing. Altogether, we uncovered the signaling networks coordinated by fungal colonies that are now increasingly associated with the infected wound microbiome, resulting in altered wound fate., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Pulmonary disease represents a major global health issue. They are commonly treated by various synthetic molecules. But, frequent high-dose of oral and injectable drugs may lead to severe side effects and this juncture demands inhaled formulations that facilitate effective drug delivery to the lower airways with negligible side effects. Natural phytoconstituents or phytoalexin (i.e. plant antibiotics) have showed an unique treatment array with minimum side effects and great capability to treat intrapulmonary and extrapulmonary diseases compared to synthetic drugs. Moreover, the progress of disciplines such as nanotechnology, material science and particle engineering allows further improvement of the treatment capability and efficiency. This article review and analyze literatures on inhaled phytoconstituents which were published in the last 10 years. Additionally, it will also offer the researcher with some basic background information for phytoconstituents profile, formulation requirements and drug delivery systems., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Fisetin (FIS), a bioactive flavonol found in the smoke tree (Cotinus coggygria), vegetables, fruits and nuts. It exhibits various therapeutic activities such as anti-oxidant, anti-inflammatory, anti-invasive, anti-tumorigenic, anti-angiogenic, anti-diabetic, cardioprotective and neuroprotective activities. In spite of the ever rising support for therapeutic activities, its clinical application is mainly limited because of poor water solubility, high lipophilicity and low oral bioavailability. Till date, numerous efforts have been made to surpass these limitations with the development of new improved delivery platforms. This article aims to review and analyze the various delivery strategies used to improve the biopharmaceutical properties of FIS. Furthermore, an attempt has been made to touch upon various features related to the progress of drug delivery including their influence on FIS chemistry, pharmacokinetics and other physicochemical attributes are discussed thoroughly., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Sarasvata ghrita (SG), a polyherbal formulation from ayurveda, an ancient medicinal system of India, has been used to improve intelligence and memory, treat speech delay, speaking difficulties and low digestion power in children., Aim of the Study: Study aimed to validate the ethno use of SG in memory enhancement through systematic scientific protocol. The effect of SG and modern extracts of ingredients of SG was compared on cognitive function and neuroprotection in amyloid-β peptide 25-35(Aβ25-35) induced memory impairment in wistar rats. Further the underlying mechanism for neuroprotective activity was investigated., Materials and Methods: SG was prepared as per traditional method, ethanolic extract (EE) was prepared by conventional method and lipid based extract was prepared by modern extraction method. All extracts were standardised by newly developed HPLC method with respect to marker compounds. SG, EE and LE were administered orally to male Wistar rats at doses of 100,200 and 400 mg/kg Body Weight by feeding needle for a period of 21 days after the intracerebroventricular administration of Aβ25-35 bilaterally. Spatial memory of rats was tested using Morris water maze (MWM) and Radial arm maze (RAM) test. The possible underlying mechanisms for the cognitive improvement exhibited by SG, EE and LE was investigated through ex-vivo brain antioxidant effect, monoamine level estimation, acetylcholine esterase (AchE) inhibitory effect and Brain-derived neurotropic factor (BDNF) levels estimation., Results: SG, EE and LE were analyzed by HPLC method, results showed that EE extract has high percent of selected phytoconstituents as compared with SG and LE. SG and LE decrease escape latency and searching distance in a dose dependant manner during MWM test. In case of RAM significant decrease in number of errors and increase in number of correct choices indicate an elevation in retention and recall aspects of learning and memory after administration of SG an LE. SG and LE extract can efficiently prevent accumulation of β-amyloid plaque in hippocampus region. There was increase in SOD, GSH, CAT and NO level and decrease in MDA levels in SG and LE administered animals. SG and LE have found to exhibit AchE inhibitiory activity and significant dose-dependant increase in BDNF level in the plasma. SG and LE significantly increased the levels of noradrenaline, dopamine and 5-hydroxytryptamine in the brain., Conclusion: The study validated the neuroprotective activity of SG. The study concludes the extraction efficiency of SG for selected phytoconstituents is less than modern methods. However the neuroprotective activity of SG and LE was found to be greater than EE., (Copyright © 2018. Published by Elsevier B.V.)

Competing Interests: Compliance with Ethical StandardsAuthors declare that they have no conflict of interest.This case report text was approved by Institutional Ethics Committee. An informed written consent was taken from the patient after explaining about the study.

Mycobacteria propelled modulation of host responses is of considerable interest in the face of emerging drug resistance. Although it is known that Abl tyrosine kinases affect entry and persistence of mycobacteria, mechanisms that couple c-Abl to proximal signaling pathways during immunity are poorly understood. Loss-of-function of c-Abl through Imatinib, in a mouse model of tuberculosis or RNA interference, identified bone morphogenesis protein (BMP) signaling as its cellular target. We demonstrate that c-Abl promotes mycobacterial survival through epigenetic modification brought about by KAT5-TWIST1 at Bmp loci. c-Abl-BMP signaling deregulated iNOS, aggravating the inflammatory balance. Interestingly, BMP signaling was observed to have far-reaching effects on host immunity, as it attenuated TLR3 pathway by engaging miR27a. Significantly, these events were largely mediated via WhiB3 and DosR/S/T but not SecA signaling pathway of mycobacteria. Our findings suggest molecular mechanisms of host pathways hijacked by mycobacteria and expand our understanding of c-Abl inhibitors in potentiating innate immune responses.

The motive of study was to develop biotinylated chitosan (BI-CHI) decorated docetaxel (DTX) loaded nanocochleates (BI-CHI-DTX-NC) to achieve controlled drug release, improve bioavailability, targeted delivery and enhanced anticancer potency with the reduced systemic toxicity of DTX. The development involved the loading of DTX to nanocochleates (DTX-NC) through conversion of dimyristoylphosphatidylglycerol-sodium (DMPG-Na) and cholesterol bearing liposome on addition of calcium ions, followed by encapsulated DTX-NC with BI-CHI (BI-CHI-DTX- NC) and compared with DTX and DTX-NC. The release of DTX indicated strong pH dependence and implies strong hydrogen-bonding between nanocochleates and DTX. Formulated BI-CHI-DTX-NC demonstrated higher in-vitro anticancer activity in biotin over expressed human breast cancer MCF-7 cells. The targeting effect for the BI-CHI-DTX-NC was also demonstrated. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 1.8 μg/ml for free DTX while it was decreased by 33.34% for the DTX-NC (1.2 μg/ml). Furthermore, the GI50 value of BI-CHI-DTX-NC was 0.2 μg/ml, i.e. an 88.89% decrease was observed as compared to DTX solution. Moreover, bioavailability of DTX from BI-CHI-DTX-NC was increased by 10-folds with longer circulation time and slower plasma elimination with low tissue distribution as compared to DTX solution. The results indicate that the BI-CHI-DTX- NC has the potential to be applied for targeting anticancer drug delivery.

The study aimed at the investigation of neuroprotective activity of macerated ethanolic extract of Indian propolis (MEEP) against β-Amyloid 25-35 (Aβ 25-35 ) induced memory impairment in Alzheimer's disease. MEEP was administrated orally to Wistar rats at doses of 100, 200 and 300mg/kg. Behavioral performances were evaluated using morris water maze and radial arm maze. At the end of behavioral study, the brains were removed and antioxidant parameters and brain monoamines were estimated. Further acetylcholinesterase (AchE) inhibition and brain-derived neurotropic factor (BDNF) were evaluated. In addition hematological parameters and histopathological tests were also carried out. In behavioral models, MEEP significantly (P<0.05) reversed the cognitive impairment of β amyloid-induced rats. The antioxidant potential was significantly increased (P<0.05) after administration of MEEP. Malondialdehyde levels were significantly (P<0.01) decreased in brain homogenate after treatment with MEEP extract as compared with diseased control group (group III). MEEP showed dose-dependent AChE inhibition and increased the levels of brain monoamines (P<0.05) as compared with group III. MEEP improved memory deficits by increasing BDNF in plasma (P<0.05). The study concludes that MEEP has anti-Alzheimer potential in rats through multiple mechanisms and further studies are ongoing for fractionation and biological screening., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

NQO1 and TRXR1 are important host reductases implicated in the regulation of inflammation and apoptosis. Although the transcriptional machinery governing these processes have been extensively investigated, the associated epigenetic regulatory events remain unclear. Here, we report that SET8, a histone H4 lysine 20 monomethylase (H4K20me1), is highly induced during Mycobacterium tuberculosis infection that orchestrates immune evasion strategies through the induction of NQO1 and TRXR1 in vivo. SET8, along with FoxO3a, mediates an active NQO1-PGC1-α complex, which promotes the anti-inflammatory M2 macrophage phenotype, and assists TRXR1-regulated arrest of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Strikingly, the loss-of-function analysis in an in vivo mouse tuberculosis model further corroborated the pivotal role of SET8-responsive NQO1 and TRXR1 in mycobacterial survival. Thus, augmenting host immune responses against Mycobacterium tuberculosis by harnessing the SET8-NQO1/TRXR1 axis with its specific and potent inhibitors could lead to promising host-directed therapeutic adjuvants for tuberculosis treatment., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Surgical site infections (SSI) are one of the most common healthcare associated infections in the low-middle income countries. Data on incidence and risk factors for SSI following surgeries in general and Obstetric and Gynecological surgeries in particular are scare. This study set out to identify risk factors for SSI in patients undergoing Obstetric and Gynecological surgeries in an Indian rural hospital., Methods: Patients who underwent a surgical procedure between September 2010 to February 2013 in the 60-bedded ward of Obstetric and Gynecology department were included. Surveillance for SSI was based on the Centre for Disease Control (CDC) definition and methodology. Incidence and risk factors for SSI, including those for specific procedure, were calculated from data collected on daily ward rounds., Results: A total of 1173 patients underwent a surgical procedure during the study period. The incidence of SSI in the cohort was 7.84% (95% CI 6.30-9.38). Majority of SSI were superficial. Obstetric surgeries had a lower SSI incidence compared to gynecological surgeries (1.2% versus 10.3% respectively). The risk factors for SSI identified in the multivariate logistic regression model were age (OR 1.03), vaginal examination (OR 1.31); presence of vaginal discharge (OR 4.04); medical disease (OR 5.76); American Society of Anesthesia score greater than 3 (OR 12.8); concurrent surgical procedure (OR 3.26); each increase in hour of surgery, after the first hour, doubled the risk of SSI; inappropriate antibiotic prophylaxis increased the risk of SSI by nearly 5 times. Each day increase in stay in the hospital after the surgery increased the risk of contacting an SSI by 5%., Conclusions: Incidence and risk factors from prospective SSI surveillance can be reported simultaneously for the Obstetric and Gynecological surgeries and can be part of routine practice in resource-constrained settings. The incidence of SSI was lower for Obstetric surgeries compared to Gynecological surgeries. Multiple risk factors identified in the present study can be helpful for SSI risk stratification in low-middle income countries.

Ethnopharmacological Relevance: Andrographis paniculata Nees (Acanthacae) have broad range of pharmacological effects such as hepatoprotective, antifertility, antimalarial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties and is widely used medicinal plant in the traditional Unani and Ayurvedic medicinal systems. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug., Aim of the Study: To evaluate the pharmacokinetic and pharmacodynamic (anti arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with naproxen (NP) after oral co-administration in wistar rats., Materials and Methods: After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with NP (7.5mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of C max , t max , t 1/2 , MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity., Results: Co-administration of NP with APE and pure AN decreased systemic exposure level of NP in vivo. The C max , t max, AUC 0-t of NP was decreased. In pharmacodynamic study, NP (10mg/kg) alone and NP+AN (10+60mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups NP+APE, APE and AN alone., Conclusion: The results obtained from this study suggested that NP, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. The knowledge regarding possible herb-drug interaction of NP might be helpful for physicians as well as patients using AP. So further studies should be done to understand the effect of other herbal ingredients of APE on NP as well as to predict the herb-drug interaction in humans., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of the study was to investigate the herb-drug interaction of Andrographis paniculata Nees (Acanthaceae) and Andrographolide (AN) with nabumetone (NAB) in wistar rats. Pharmacokinetic and pharmacodynamic interactions were studied after co-administration of APE and AN with NAB in Wistar rats. In pharmacokinetic studies, significant decrease in Cmax, AUC 0-t and AUC 0-∞ of 6-MNA after co-administration with pure AN and APE has been observed. T max of 6-MNA has been increased to 2 h from 1.5 h in AN + NAB treated group. Changes in mean residential time, clearance and volume of distribution of 6-MNA in APE + NAB treated group and AN + NAB treated group indicated interference of other components of APE other than AN. In pharmacodynamic study, significant decrease in antiarthritic activity of NAB on concomitant administration with APE and AN has been observed. The study concludes that NAB exhibits pharmacokinetic and pharmacodynamic interactions with APE and AN in rats thus alarms the concomitant use of herbal preparations containing APE and AN with NAB. Further study is needed to understand the mechanism and predict the herb-drug interaction in humans. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Foamy macrophages (FM)s harbor lipid bodies that not only assist mycobacterial persistence within the granulomas but also are sites for intracellular signaling and inflammatory mediators which are essential for mycobacterial pathogenesis. However, molecular mechanisms that regulate intracellular lipid accumulation in FMs during mycobacterial infection are not clear. Here, we report for the first time that jumonji domain containing protein (JMJD)3, a demethylase of the repressive H3K27me3 mark, orchestrates the expression of M. tuberculosis H37Rv-, MDR-JAL2287-, H37Ra- and M. bovis BCG-induced genes essential for FM generation in a TLR2-dependent manner. Further, NOTCH1-responsive RNA-binding protein MUSASHI (MSI), targets a transcriptional repressor of JMJD3, Msx2-interacting nuclear target protein, to positively regulate infection-induced JMJD3 expression, FM generation and M2 phenotype. Investigations in in vivo murine models further substantiated these observations. Together, our study has attributed novel roles for JMJD3 and its regulators during mycobacterial infection that assist FM generation and fine-tune associated host immunity.

Ethnopharmacological Relevance: Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug, Aim of the Study: To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats., Materials and Methods: After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity., Results: Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone., Conclusion: The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible herb-drug interaction with ETO., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: Curcumin has a wide range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antibacterial, wound healing, antiatherosclerotic, hepatoprotective and anti-carcinogenic. However, its clinical applications are limited owing to its poor aqueous solubility, multidrug pump P-gp efflux, extensive in vivo metabolism and rapid elimination due to glucuronidation/sulfation., Purpose: The objective of the current work was to prepare novel curcumin loaded mixed micelles (CUR-MM) of Pluronic F-127 (PF127) and Gelucire® 44/14 (GL44) in order to enhance its oral bioavailability and cytotoxicity in human lung cancer cell line A549., Study Design: 3(2) Factorial design was used to assess the effect of formulation variables for optimization of mixed micelle batch., Methods: CUR-MM was prepared by a solvent evaporation method. The optimized CUR-MM was evaluated for size, entrapment efficiency (EE), in vitro curcumin release, cytotoxicity and oral bioavailability in rats., Results: The average size of CUR-MM was found to be around 188 ± 3 nm with an EE of about 76.45 ± 1.18% w/w. In vitro dissolution profile of CUR-MM revealed controlled release of curcumin. Additionally, CUR-MM showed significant improvement in cytotoxic activity (3-folds) and oral bioavailability (around 55-folds) of curcumin as compared to curcumin alone. Such significant improvement in cytotoxic activity and oral bioavailability of curcumin when formulated into mixed micelles could be attributed to solubilization of hydrophobic curcumin into micelle core along with P-gp inhibition effect of both, PF127 and GL44., Conclusion: Thus the present work propose the formulation of mixed micelles of PF127 and GL44 which can act as promising carrier systems for hydrophobic drugs such as curcumin with significant improvement in their oral bioavailability., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: The current study was designed to investigate the influence of monofloral Indian mustard bee pollen (MIMBP) and processed monofloral Indian mustard bee pollen (PMIMBP) supplementation on chronic swimming exercise-induced oxidative stress implications in the gastrocnemius muscle of Wistar rats., Methods: MIMBP was processed with an edible lipid-surfactant mixture (Captex 355:Tween 80) to increase the extraction of polyphenols and flavonoid aglycones as analyzed by UV spectroscopy and high performance liquid chromatography-photo diode array. Wistar rats in different groups were fed with MIMBP or PMIMBP supplements at a dose of 100 mg/kg, 200 mg/kg and 300 mg/kg individually, while being subjected to chronic swimming exercise for 4 weeks (5 d/wk). Various biochemical [superoxide dismutase (SOD), glutathione (GSH), malonaldehyde (MDA), nitric oxide (NO), and total protein content], mitochondrial (Complex I, II, III, and IV enzyme activity), and molecular (myostatin mRNA expression) parameters were monitored in the gastrocnemius muscle of each group., Results: Administration of both MIMBP (300 mg/kg) and PMIMBP (100 mg/kg, 200 mg/kg, and 300 mg/kg) wielded an antioxidant effect by significantly improving SOD, GSH, MDA, NO, and total protein levels. Further MIMBP (300 mg/kg) and PMIMBP (200 mg/kg and 300 mg/kg) significantly improved impaired mitochondrial Complex I, II, III, and IV enzyme activity. Significant down-regulation of myostatin mRNA expression by MIMBP (300 mg/kg) and PMIMBP (200 mg/kg and 300 mg/kg) indicates a muscle protectant role in oxidative stress conditions., Conclusion: The study establishes the antioxidant, mitochondrial upregulatory, and myostatin inhibitory effects of both MIMBP and PMIMBP in exercise-induced oxidative stress conditions, suggesting their usefulness in effective management of exercise-induced muscular stress. Further, processing of MIMBP with an edible lipid-surfactant mixture was found to improve the therapeutic efficiency of pollen.

Herbal medicine, the backbone of traditional medicine, has played an important role in human health and welfare for a long period. Traditional therapeutic approaches of regional significance are found in Africa, South and Central America, China, India, Tibet, Indonesia, and the Pacific Islands. The considerable scientific significance and commercial potential of traditional medicines have resulted in increased international attention and global market demands for herbal medicines, especially Chinese herbal medicines. Herbal medicines currently are the primary form of health care for the poor in the developing countries, and also are widely used as a supplement or substitute for conventional drugs in developed countries. These traditional medicines have a pivotal role in the treatment of various ailments and more than 50% of drugs used in Western pharmacopoeia are isolated from herbs or derived from modifications of chemicals found in plants. Herbal medicines usually contain a complex mixture of various bioactive molecules, which make its standardization complicated, and there is little information about all compounds responsible for pharmacological activity. Several research papers have been published that claim pharmacological activity of herbal medicines but few are discussing the role of the exact phytoconstituent. Understanding the pharmacokinetic profile of such phytoconstituents is essential. Although there are research papers that deal with pharmacokinetic properties of phytoconstituents, there are a number of phytoconstituents yet to be explored for their kinetic properties. This article reviews the pharmacokinetic profile of 50 different therapeutically effective traditional medicinal plants from the year 2003 onward.

Macrophages regulate cell fate decisions during microbial challenges by carefully titrating signaling events activated by innate receptors such as dectin-1 or Toll-like receptors (TLRs). Here, we demonstrate that dectin-1 activation robustly dampens TLR-induced proinflammatory signature in macrophages. Dectin-1 induced the stabilization of β-catenin via spleen tyrosine kinase (Syk)-reactive oxygen species (ROS) signals, contributing to the expression of WNT5A. Subsequently, WNT5A-responsive protein inhibitors of activated STAT (PIAS-1) and suppressor of cytokine signaling 1 (SOCS-1) mediate the downregulation of IRAK-1, IRAK-4, and MyD88, resulting in decreased expression of interleukin 12 (IL-12), IL-1β, and tumor necrosis factor alpha (TNF-α). In vivo activation of dectin-1 with pathogenic fungi or ligand resulted in an increased bacterial burden of Mycobacteria, Klebsiella, Staphylococcus, or Escherichia, with a concomitant decrease in TLR-triggered proinflammatory cytokines. All together, our study establishes a new role for dectin-1-responsive inhibitory mechanisms employed by virulent fungi to limit the proinflammatory environment of the host., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4 and karyopherin-2 (KPNA2) have been helpful in differentiating ovarian yolk sac tumor from dysgerminoma, teratomas, and other pictures of hepatoid, endometrioid, clear cell carcinomatous, and adenocarcinomatous tissues with varied malignant potential. Before platinum therapy, these tumors were almost fatal in children. Fertility-conserving surgery with bleomycin, etoposide, and cisplatin has dramatically changed the survival rates in these patients. This modality gives cancer cure with healthy offspring to female patients with childhood ovarian tumor. Evidence also supports this protocol resulting in successful pregnancy rates and safety of cytotoxic drugs in children born to these patients.

This article describes the design of biphenyl moiety linked with aryl piperazine and syntheses of fourteen 1-(biphenyl-4-yl)-2-[4-(substituted phenyl)-piperazin-1-yl]ethanone derivatives along with their pharmacological evaluation for antipsychotic activity and computational studies including quantitative structure activity relationship (QSAR) and descriptor based similarity study. All compounds were found to exhibit considerable anti-dopaminergic and anti-serotonergic activity in behavioural models. Among all derivatives, compound 1-(biphenyl-4-yl)-2-[4-(2-methoxyphenyl)-piperazin-1-yl]ethanone (3c) and 1-(biphenyl-4-yl)-2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethanone (3k) showed impressive antipsychotic profile with lower potency for catalepsy induction. These results were found to be sturdily matching with docking study in designing of compounds with homology model of human dopamine D2 receptor. Also the QSAR study strongly supports the obtained results., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: To isolate and characterize the alcohol-producing yeasts from Woodfordia fruticosa flowers, which are used for the induction and maintenance of fermentation in the making of Ayurvedic formulations., Materials and Methods: Initially twenty four yeasts strains were isolated on MGYP agar plate. Among them, four strains were selected for further studies on the basis of their alcohol generation capacity using jaggery media (50% w/v). Physiological, biochemical and genetic characterization (18S rRNA sequencing) of selected strains were carried out., Results: Physiological, biochemical and genetic characterization (18S rRNA sequencing) confirmed the strains as Saccharomycopsis fibuligera Jm.8, S. fibuligera Jm.10, S. fibuligera Jm.16 and Saccharomyces cerevisiae Jm.20. Under the controlled conditions, S. cerevisiae Jm.20 produced 69.57 g/l of alcohol, whereas remaining strains produced the alcohol in the range of 6.04-7.32 g/l., Conclusion: Among selected strains, strains S. fibuligera are a newer in the flowers. Kinetic study of alcohol generation revealed the strain S. cerevisiae Jm.20 can be efficiently used in making of fermented Ayurvedic formulations instead of use W. fruticosa flowers.

Objectives: Antibacterial drugs (hereafter referred to as antibiotics) are crucial to treat infections during delivery and postpartum period to reduce maternal mortality. Institutional deliveries have the potential to save lives of many women but extensive use of antibiotics, add to the development and spread of antibiotic resistance. The aim of this study was to present antibiotic prescribing among inpatients during and after delivery in a non-teaching, tertiary care hospital in the city of Ujjain, Madhya Pradesh, India., Methods: A prospective cross-sectional study was conducted including women having had either a vaginal delivery or a cesarean section in the hospital. Trained nursing staff collected the data on daily bases, using a specific form attached to each patient file. Statistical analysis, including bivariate and multivariable logistic regression was conducted., Results: Of the total 1077 women, 566 (53%) had a vaginal delivery and 511 (47%) had a cesarean section. Eighty-seven percent of the women that had a vaginal delivery and 98% of the women having a cesarean section were prescribed antibiotics. The mean number of days on antibiotics in hospital for the women with a vaginal delivery was 3.1 (±1.7) and for the women with cesarean section was 6.0 (±2.5). Twenty-eight percent of both the women with vaginal deliveries and the women with cesarean sections were prescribed antibiotics at discharge. The most commonly prescribed antibiotic group in the hospital for both the women that had a vaginal delivery and the women that had a cesarean section were third-generation cephalosporins (J01DD). The total number of defined daily doses (DDD) per100 bed days for women that had a vaginal delivery was 101, and 127 for women that had a cesarean section., Conclusions: The high percentage of women having had a vaginal delivery that received antibiotics and the deviation from recommendation for cesarean section in the hospital is a cause of concern. Improved maternal health and rational use of antibiotics are intertwined. Specific policy and guidelines on how to prescribe antibiotics during delivery at health care facilities are needed. Additionally, monitoring system of antibiotic prescribing and resistance needs to be developed and implemented.

Background: Ashwagandharishtha is a liquid polyherbal formulation traditionally prepared by fermentation process using the flowers of Woodfordia fruticosa. It contains roots of Withania somnifera as a major crude drug. Alcohol generated during the fermentation causes the extraction of water insoluble phytoconstituents. Yeasts present on the flowers are responsible for this fermentation., Methods: Total nine formulations of ashwagandharishtha were prepared by fermentation process using traditional Woodfordia fruticosa flowers (ASG-WFS) and using yeasts isolated from the same flowers. During fermentation, kinetic of alcohol generation, sugar consumption, changes in pH and withanolides extraction were studied. All the formulations were tested for in vitro antioxidant potential by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, hydrogen peroxide scavenging and total reducing power assay. The results were compared with standard ascorbic acid., Results: Traditional formulation (ASG-WFS) showed the highest activity (p < 0.001) relative to other formulations and standard ascorbic acid. ASG-WFS showed significant (DPPH) free radical scavenging (78.75%) and hydrogen peroxide scavenging (69.62%) at the concentration of 1000 μg/mL and 100 μg/mL, respectively., Conclusion: Traditional process is the best process for preparing ashwagandharishtha to obtain significant antioxidant activity.

Background: Commensal Escherichia coli are a prominent reservoir of genes coding for antibiotic resistance and also responsible for endogenous infections in pregnant women. We studied the factors in pregnant women associated with carriage of multi-drug resistant (MDR) E. coli and genetic determinants of antibiotic resistance in them., Methods: Women attending to Obstetric and Gynaecology department outpatient clinics for routine antenatal check-up were administered a questionnaire. Peri-anal swabs were collected for culture isolation and identification of E.coil. Antibiotic sensitivity was done using the Kirby-Bauer disc diffusion method as recommended by the CLSI guidelines. MICs for quinolones and third generation cephalosporins were done using the agar dilution method. Genes coding for production of beta lactamses and for the quinolone resistance determinant were screened by polymerase chain reaction. Rep-PCR was done on MDR isolates for detecting possible genetic similarity. Multiple logistic regression models were used to determine the independent factors associated with carriage of MDR isolates., Results: A total of 710 isolates of E. coli from 710 women (mean age 26 years) were included in the study. Resistance to at least one antibiotic tested was detected in 94% of the E. coli isolates. A total of 109 isolates were ESBL producing and 35 isolates were MDR. In the MDR isolates MIC(50) and MIC(90) for quinolones and third generation cephalosporins were high for those isolates that carried bla(TEM) gene (26 isolates) and bla(CTX-M) gene (24 isolates). Both bla(TEM) and bla(CTX-M) genes were detected in 19 isolates. The commonest Plasmid Mediated Quinolone Resistance (PMQR) gene identified was aac(6')-Ib-cr (n = 23/25). All isolates carrying the PMQR genes were also positive for bla(CTX-M) and bla(TEM) gene. Mutations in gyr A and par C genes were present in all 35 MDR isolates. The statistically significant risk factors for carriage of MDR E. coli were graduate or post-graduate education, a self-employed status, a family size of more than 10 members, antibiotic usage in last four weeks, and history of hospitalization in the last four weeks., Conclusions: The presence of genes coding for extended spectrum of beta lactamases and plasmid mediated quinolone resistance in commensal E. coli is disconcerting. The study provides strong basis good antibiotic stewardship.

Context: Caffeine/oxalic acid 2:1 cocrystal exhibited superior stability to humidity over caffeine, but compressional behavior is not studied yet., Objective: To compare compressional properties of caffeine/oxalic acid 2:1 cocrystal obtained by different cocrystallization techniques., Materials and Methods: Cocrystal was obtained by solvent precipitation and ultrasound assisted solution cocrystallization (USSC) and characterized by X-ray powder diffraction and scanning electron microscopy. Compaction study was carried out at different compaction forces. Compact crushing strength, thickness and elastic recovery were determined., Results and Discussion: Compaction was in order, caffeine > solvent precipitation cocrystal > USSC cocrystal. Caffeine exhibited sticking and lamination, where solvent precipitation compacts showed advantage. Caffeine and solvent precipitation compacts showed sudden drop in compactability, higher elastic recovery with severe lamination at 20,000 N. This was due to overcompaction. Crystal habit of two cocrystal products was same, but USSC cocrystals were difficult to compact. Uniform needle shaped USSC cocrystals must be difficult to orient in different direction and fracture during compression. Elastic recovery of USSC cocrystals was also more compared to other powders indicating less fracture and poor bonding between particles resulting in poor compaction., Conclusion: Cocrystal formation did not improve compressional property of caffeine. Cocrystals exposed to different crystallization environments in two techniques may have resulted in generation of different surface properties presenting different compressional properties.

There is paucity of surveillance studies on antibiotic resistance in commensal Escherichia coli. The main aim of this cross-sectional study was to determine factors associated with peri-anal carriage of multi-resistant E. coli by healthy postmenopausal women. A structured questionnaire was completed for consecutive healthy postmenopausal women aged 45 y and above attending the outpatient clinics of the Department of Obstetrics and Gynaecology at R.D. Gardi Medical College, Ujjain, India. Antibiotic susceptibility testing was done by the Kirby-Bauer disk diffusion method, as recommended in the Clinical and Laboratory Standards Institute guidelines. The study showed that 28% of healthy women carried multidrug-resistant (MDR) E. coli in the peri-anal region. The factors significantly associated with carriage of MDR E. coli were family size > 10 (OR 8.23, 95% CI 2.73-24.73; p < 0.001), antibiotic use in the past 2 weeks (OR 5.39, 95% CI 2.36-12.34; p < 0.001), and hospitalization in the past 2 weeks (OR 4.02, 95% CI 1.73-9.31; p = 0.001). This is the first study from India reporting the MDR E. coli carriage rate in healthy women aged over 45 y.