Product development and characterization of the Ayurvedic herbo-mineral-metallic compound- Hridayarnava Rasa.

BACKGROUND: Herbo-mineral-metallic formulations are an inseparable part of the Ayurveda system of traditional medicine. Hridayarnava Rasa (HR) is a preparation containing metals like copper, sulphur, and mercury in processed forms and other herbs that do not produce toxic effects and adverse drug reactions when taken in appropriate dosage. Ayurveda practitioners use it in treating cardiac diseases like hypertension, cardiotoxicity and many more. The rasa-aushadhis possess characteristics such as rapid efficacy, little dosage required, and extensive therapeutic applicability. Hridayarnava Rasa [AFI Part-1, 20:55] has been employed for the treatment of various diseases from ancient times. A systematic study of these formulations manufacturing is required to maintain their quality, safety, and efficacy is a need of time to protect the immense faith of patients in Ayurveda. OBJECTIVES: The present study aimed to prepare HR as per standard operating procedures mentioned in the classical text and to characterize it physio-chemically using advanced analytical techniques. MATERIALS AND METHODS: HR was prepared and physicochemical analyses and assay of elements by ICP-AES were carried out as per Ayurvedic Pharmacopoeia of India (API). Powder X-ray diffraction (XRD), Field emission gun scanning electron microscopy with energy dispersive spectroscopy (FEG SEM, EDAX), CHNS-O analysis, Fourier Transform Infrared Spectroscopy (FTIR), Thermo-gravimetric analysis (TGA), Particle size distribution analysis (PSD) was carried out. RESULTS: The XRD analysis of HR showed the presence of unreacted sulphur and sulfides of copper and mercury. FEG SEM revealed the particles in the form of aggregates as nanocrystallites in the range of 100-1000 nm. Elemental analysis showed the presence of copper, sulphur, and mercury in major, along with traces of iron, calcium, sodium, potassium, and magnesium. In FTIR analysis, 18 peaks were observed, which strongly suggests the presence of various organic groups. In the TGA, four peaks were seen, which can be attributed to sulphur volatilization and oxidative changes in mercury. In PSD analysis, 50% of the material was found below 16.40 µm. CONCLUSION: To establish a piece of fundamental knowledge and ensure uniformity of these rasa-aushadhis, it is imperative to conduct an analysis of their characteristics as per classical texts and modern analytical techniques. Additionally, it is crucial to investigate the significance of each procedural step included in the preparation process. The inferences drawn are helpful as an essential aid for quality assurance and standardization of this herbo-mineral-metallic formulation.

Bacillus sp. extract used to fabricate ZnO nanoparticles for their antagonist effect against phytopathogens.

In order to achieve the food demand of a growing population, agricultural productivity needs to be increased by employing safe strategies. In the present study we have evaluated ZnONPs that were synthesized from the culture supernatant of Bacillus subtilis. Bio mimetically synthesized ZnONPs showed a surface resonance peak of 355 nm corresponding to NPs formation. Further, NPs were examined for their size, shape and element confirmation by DLS, AFM, SEM, TEM and EDAX, which confirmed the synthesized NPs were nearly spherical in size with average diameter of 32 nm by TEM. Surface charge of + 34.3 mV was observed for NPs with a low poly-dispersity index of 0.21. In vitro efficacy studies against fungi Colletotrichum capsici, Sclerotium rolfsii, Alternaria solani and Fusarium oxysporum f. sp. cicero showed up to 99% mycelial growth inhibition at 0.125% ZnONPs. Further, in-vitro disk-diffusion assay showed inhibition zones of 23 ± 0.4 mm and 12.67 ± 0.24 mm for Xanthomonas axonopodis pv. punicae (Xap) and Xanthomonas oryzae pv. oryzae (Xoo) bacterial cultures. Plant toxicity study was observed that ≤ 0.14% NPs concentration was safe under greenhouse conditions. Overall, the present study emphasizes the potential effect of ZnONPs against agricultural pathogens which play an important role in agriculture production.

Clinicopathological Evaluation of Tobacco-related Oral Mucosal Lesions.

AIM: To clinically evaluate the nature of precancerous and cancerous lesions associated with tobacco consumption habit and to correlate clinical profile with the histopathological findings of clinically suspected precancerous and cancerous lesions. MATERIALS AND METHODS: These included the examination of patients who visited the outpatient department (OPD) of the institute that includes 1,500 patients who had tobacco chewing habits were classified into the following two groups according to their characteristics. The study group comprised 270 patients, of which 170 gave consent for biopsy and 100 patients who not gave consent were counseled for tobacco cessation. RESULTS: Among 270 patients, the highest number of patients, 146 (54.07%) patients, were found to be smokeless tobacco consumers followed by 65 (24.07%) patients who were smoked tobacco consumers while 59 (21.85%) patients were found to have both the habits. Wide variation was noted in duration and frequency of habit. Most prevalent site was the buccal mucosa affected in 138 (51.11%) patients who consumed both smoked as well as smokeless tobacco. And on clinical examination, 138 (51%) patients had leukoplakia followed by 54 (20%) patients with oral squamous cell carcinoma and 40 (15%) patients with oral submucous fibrosis (OSMF). Other patients were tobacco pouch keratosis 17 (6%), smoker's melanosis 8 (3%), smoker's palate 7 (3%), and erythroplakia 6 (2%). The patients who gave consent (170 patients) were evaluated histopathologically to correlate with clinical findings. CONCLUSION: Tobacco-related oral lesions are also high, which brings an alarming signal toward the development of cancer. Our contribution as healthcare providers can be made by conducting more oral health education programs and educating the general population about the adverse effects of tobacco. The appropriate clinical assessment and categorization of all these lesions aided us in motivating patients to undergo necessary treatments and also to discontinue their habits in order to prevent deterioration of their conditions. CLINICAL SIGNIFICANCE: Set up de-addiction centers in dental colleges and help tobacco users in discontinuing their habits. Interestingly, this study also served as a mirror for those patients who were unaware of the lesions they were giving abode to in their oral cavities.

Glucose derived carbon nanosphere (CSP) conjugated TTK21, an activator of the histone acetyltransferases CBP/p300, ameliorates amyloid-beta 1-42 induced deficits in plasticity and associativity in hippocampal CA1 pyramidal neurons.

The master epigenetic regulator lysine acetyltransferase (KAT) p300/CBP plays a pivotal role in neuroplasticity and cognitive functions. Recent evidence has shown that in several neurodegenerative diseases, including Alzheimer's disease (AD), the expression level and function of p300/CBP are severely compromised, leading to altered gene expression causing pathological conditions. Here, we show that p300/CBP activation by a small-molecule TTK21, conjugated to carbon nanosphere (CSP) ameliorates Aß-impaired long-term potentiation (LTP) induced by high-frequency stimulation, theta burst stimulation, and synaptic tagging/capture (STC). This functional rescue was correlated with CSP-TTK21-induced changes in transcription and translation. Mechanistically, we observed that the expression of a large number of synaptic plasticity- and memory-related genes was rescued, presumably by the restoration of p300/CBP mediated acetylation. Collectively, these results suggest that small-molecule activators of p300/CBP could be a potential therapeutic molecule for neurodegenerative diseases like AD.

Heterogeneous Distribution of Genetic Mutations in Myosin Binding Protein-C Paralogs.

Myosin binding protein-C (MyBP-C) is a sarcomeric protein which regulates the force of contraction in striated muscles. Mutations in the MYBPC family of genes, including slow skeletal (MYBPC1), fast skeletal (MYBPC2) and cardiac (MYBPC3), can result in cardiac and skeletal myopathies. Nonetheless, their evolutionary pattern, pathogenicity and impact on MyBP-C protein structure remain to be elucidated. Therefore, the present study aimed to systematically assess the evolutionarily conserved and epigenetic patterns of MYBPC family mutations. Leveraging a machine learning (ML) approach, the Genome Aggregation Database (gnomAD) provided variants in MYBPC1, MYBPC2, and MYBPC3 genes. This was followed by an analysis with Ensembl's variant effect predictor (VEP), resulting in the identification of 8,618, 3,871, and 3,071 variants in MYBPC1, MYBPC2, and MYBPC3, respectively. Missense variants comprised 61%-66% of total variants in which the third nucleotide positions in the codons were highly altered. Arginine was the most mutated amino acid, important because most disease-causing mutations in MyBP-C proteins are arginine in origin. Domains C5 and C6 of MyBP-C were found to be hotspots for most mutations in the MyBP-C family of proteins. A high percentage of truncated mutations in cMyBP-C cause cardiomyopathies. Arginine and glutamate were the top hits in fMyBP-C and cMyBP-C, respectively, and tryptophan and tyrosine were the most common among the three paralogs changing to premature stop codons and causing protein truncations at the carboxyl terminus. A heterogeneous epigenetic pattern was identified among the three MYBP-C paralogs. Overall, it was shown that databases using computational approaches can facilitate diagnosis and drug discovery to treat muscle disorders caused by MYBPC mutations.

Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy.

Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10-7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (odds ratio 6.7-58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP.

Pharmacognostical and phytochemical screening of root and fruit of Ficus semicordata Buch.-Ham. Ex Sm. - An extra pharmacopoeial drug.

Introduction: Root and fruits of Bhumi Udumbara (Ficus semicordata Buch.-Ham. ex Sm.) are traditionally used in the treatment of aphthous complaints, leprosy, headache, abdominal diseases, bladder ailments, visceral obstruction, and various disorders. Aim: Present study reports the microscopic including powder microscopy, physiochemical and preliminary phytochemical characters of root and fruit of F. semicordata. Materials and methods: Root and fruit of the plant, after proper authentication, were evaluated following standard pharmacopoeial recommended procedures. Results: Striking characters of the F. semicordata root is the presence of profusely branched root-like structures, nearer to the trunk, and reaches the ground as a supporting root (aerial root or false root). The diagrammatic section of the root, circular in outline, made up of an outer cork, followed by cortex, vascular bundle, and central pseudo pith. Fruit is shortly peduncled, in pairs or clusters, globose in shape, hispid and warted surface, reddish brown in color. Loss on drying at 110°C was found to be 10.54% and 11.73% of root and fruit respectively. High-performance thin-layer chromatography results showed 2 peaks at 254 and 366 nm of root and 3 peaks at 254 and 1 peak at 366 nm of fruit respectively. Conclusion: F. semicordata is a small or medium-sized evergreen tree, bears a supporting root (aerial root or false root) nearer to the trunk region. Root reddish brown in color with smooth surface, prominent nodes, and internodes, presence of fruits over nodes and internodes is the key identifying character. Stone cells found in root and the presence of pollen grains, simple starch grains, and compound starch grains in fruit are the diagnostic characteristics of F. semicordata.

Association and functional significance of genetic variants present in regulatory elements of SERPINB5 gene in gallbladder cancer.

SERPINB5 is a mammary serine protease inhibitor, which is involved in various cellular functions. The aberrant expression of SERPINB5 is reported in many cancers along with GBC but limited information is available about its role in genetic predisposition for GBC. We carried out case-control study in 206 cases and 219 controls. Promoter SNPs were genotyped by Sanger's sequencing. In-silico promoter analysis and luciferase reporter assay were done to elucidate the role of promoter variants in regulation of SERPINB5 expression. Out of four SNPs, three SERPINB5 promoter variants showed association with GBC in different models. The 'C' allele of variant rs17071138 was found to be significantly associated with GBC (p = 0.017). The 'T' allele of rs3744940 significantly increased the risk for GBC in dominant (p = 0.035) and additive models (p = 0.005). Also, rs3744941 'T' allele increased the risk for GBC by dominant (p = 0.042) as well as additive models (p = 0.016). In-silico promoter analysis and luciferase reporter assay revealed the probable regulatory role of the SERPINB5 promoter variant rs17071138 on the expression. Overall, our study reveals the genetic association of SERPINB5 promoter variants with GBC and possible role of rs17071138 in the regulation of expression.

Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM. METHODS AND RESULTS: Here, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect. CONCLUSIONS: Our study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.

Label-Free Protein Glycosylation Analysis Using NanoMonitor-An Ultrasensitive Electrochemical Biosensor.

Glycans (oligosaccharide chains attached to glycoproteins) are a promising class of biomarkers, found in body fluids such as serum, saliva, urine, etc., that can be used for the diagnosis of disease conditions. Subtle changes in glycans resulting from altered glycosylation machinery have been reported during various diseases, including carcinogenesis. In this article, we detail protocols for the rapid, label-free analysis of glycans using a previously developed highly sensitive and selective electrochemical impedance spectroscopy-based biosensing diagnostic platform called "NanoMonitor." The glycosensor operation is based on the specific affinity capture of the target glycans on the sensor surface by glycan-binding proteins known as lectins. This glycan-lectin binding activity modulates the impedance of the electrical double layer at the buffer-electrode interface. Protocols for the preparation of glycoprotein samples and glycosylation analysis using NanoMonitor and lectin-based ELISA are described here. The data obtained using these protocols show that NanoMonitor is capable of distinguishing between glycoform variants of the glycoprotein fetuin and glycoproteins derived from cultured human pancreatic cancer cells with high sensitivity (orders of magnitude higher than lectin-based ELISA) and selectivity. The results obtained indicate that NanoMonitor protocols can be further developed to enable use of NanoMonitor as a handheld electronic biosensor device for routine multiplexed detection of glycan biomarkers from clinical samples. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Preparing the NanoMonitor surface for glycan biosensing Support Protocol: Synthesis of glycoform variants of fetuin Basic Protocol 2: Performing Electrochemical Impedance Spectroscopy (EIS) for analyzing glycoprotein structures.

SERPINB5 Genetic Variants rs2289519 and rs2289521 are Significantly Associated with Gallbladder Cancer Risk.

Serine protease inhibitor b5 (SERPINB5) is a tumor suppressor gene that plays a critical role in various cellular processes. In gallbladder cancer (GBC), SERPINB5's aberrant expression is reported but its role in genetic predisposition is not known. We enrolled 270 cases and 296 controls and genotyped them for single nucleotide polymorphisms (SNPs) using direct DNA sequencing, followed by genotype-phenotype analysis in GBC and other cancer cell lines. Luciferase assay was done to determine the role of rs2289521 SNP on expression regulation. We found that two SERPINB5 variants rs2289519 and rs2289521 are significantly associated with GBC and contribute to genetic predisposition. The TT genotype of variant rs2289519 was found to be significantly associated (p = 0.008) with GBC in a recessive model. C allele of rs2289521 increased the risk for GBC significantly at genotypic (CT, p = 0.026) and allelic (p = 0.04) levels. In silico analysis and luciferase assay uncovered the probable regulatory role of the rs2289521 variant on expression. Genotype-phenotype correlation in GBC and breast cancer cell lines showed reduced expression of SERPINB5 in the presence of C allele that was consistent with the result of luciferase assay. Overall, our study reveals the genetic association of two SERPINB5 variants with GBC and rs2289521's possible role in the regulation of expression.

Canal occlusion in cemented primary total hip replacement: autologous compacted bone block compared to a commercially available gelatine plug.

AIMS: To evaluate the stability of 2 canal occlusion systems; an autologous, compacted bone block and the biodegradable C-plug. We also sought to investigate any relationship between stability of the systems and the quality of cementation. A retrospective radiographic comparative review was conducted. METHODS: A total of 203 consecutive patients were analysed, 89 received an autologous bone block and 114 had C-plugs. There was no significant differences between the groups in terms of age, sex and primary diagnosis. The mean cement tail length in the bone block group (6.42 mm; range 0-31) was significantly shorter than in the C-plug group (17.11 mm; range 0-65.7). RESULTS: The proportion of patients with good quality of cementation (Barrack grade A) was significantly higher in the bone block group (80.6%) as compared to the C-plug group (56%) (p < 0.001). There was a negative correlation between the length of the cement tail and the Barrack grade, indicating that a short cement tail is associated with better quality cementation. CONCLUSIONS: We have shown that improved cement penetration and shorter cement tails can be achieved with the cheapest of all options for canal occlusion, an autologous compacted bone block and hence recommend this technique.

Shodhana (processing) of Rakta-Snuhi (Euphorbia caducifolia Haines.) latex with Chincha (Tamarindus indica L.) leaf juice: A pharmaceutical analysis.

BACKGROUND: Latex of Euphorbia caducifolia Haines. (Euphorbiaceae), botanical source of Rakta Snuhi, a caustic irritant, is being used in different Ayurvedic therapeutics, after proper processing (Shodhana) in some specific media. Shodhana of Snuhi latex with Chincha-Patra Swarasa (juice of tamarind leaves) using Raudra Yantra (instrument/pot kept under sunlight for drying) has been recommended in Ayurveda texts. Snuhi is one of the Upavisha (sub toxic group of herbal drugs) and a well-known plant in the Indian system of medicine. It is used in pharmaceutical procedures like preparation and processing of drugs. AIM: The aim of the study was to carry out Shodhana of E. caducifolia latex with Chincha-Patra Swarasa. MATERIAL AND METHODS: Fresh latex of Snuhi was collected from the Sapada area of Jamnagar, Gujarat and fresh leaves of Tamarindus indica L. were collected from the herbal garden of the university and Swarasa was extracted by traditional expression technique. Shodhana of Snuhi Kshira was done under sunlight dried and shade dried method by mixing it with leaf juice of Tamarindus indica L. in a glass bowl in different ratio i.e. Kshira: leaf juice was 8:4, 8:2, 8:1 respectively. RESULTS: This study reveals certain changes in physico-chemical parameters (pH) and organoleptic characters of processed E. caducifolia latex by Tamarind leaf juice both in shade-dried and sunlight-dried samples. Under HPTLC, Shodhana of E. caducifolia latex with Tamarind leaf juice alters the number of spots both sunlight-dried and shade-dried samples. In sun-dried sample, the number of spots increased when the concentration of Tamarind leaf juice is decreased in HPTLC study. The study reveals that in case of shade-dried Shodhita (processed) Snuhi latex sample, the concentration of lupeol increases with the increasing quantity of Tamarind leaf juice. CONCLUSION: Shodhana with Tamarind leaf juice changes both qualitative and quantitative property of Snuhi latex.

Standard operating procedure of Purification of Chitraka (Plumbago zeylanica Linn.) along with pharmacognostical and analytical profiles of Plumbagin.

INTRODUCTION: Shodhana (purification) is the process by which one can remove the impurity or toxicity of the raw drug and make the drug suitable for therapeutic purpose. Chitraka (Plumbago zeylanica Linn.) is well known drug in Ayurveda and root of this plant is being used for therapeutic purpose and requires purification before used as a medicine. AIMS AND OBJECTIVE: There is no data available for pharmacognostical and analytical profile of processed Chitraka, hence it was planned to develop SOP of processed Chitraka for its identity, purity and strength through pharmacognostical and analytical profile. MATERIALS AND METHODS: Chitraka roots were procured from Pharmacy, Gujarat Ayurved University, Jamnagar. Purification was done in five batches with Churnodaka (lime water). Organoleptic characters, microscopic features, pH, loss on drying, ash value, water soluble extracts, methanol soluble extracts and plumbagin quantification through high-performance thin layer chromatography (HPTLC) were carried out, before and after the purification. RESULTS: Average 98.07% yield of Chitraka was obtained after purification. Differences were found in the processed samples of Chitraka in organoleptic features, pharmacognostical characters and physicochemical parameters, which show the impact of purification procedure on Chitraka. In HPTLC profile, plumbagin content was 0.29% in unpurified Chitraka powder, where in it was noted 0.98% after purification. CONCLUSION: Increase in plumbagin content through pharmaceutical process of Chitraka purification with lime water indicates that, this operating procedure is simple, convenient and can be considered as standard procedure. The organoleptic features, pharmacognostical characters, values of physicochemical parameters and quantity of plumbagin of purified Chitraka powder may be utilized for quality assurance in future studies.

Functional interplay between YY1 and CARM1 promotes oral carcinogenesis.

Coactivator associated arginine methyltransferase 1 (CARM1) has been functionally implicated in maintenance of pluripotency, cellular differentiation and tumorigenesis; where it plays regulatory roles by virtue of its ability to coactivate transcription as well as to modulate protein function as an arginine methyltransferase. Previous studies establish an oncogenic function of CARM1 in the context of colorectal and breast cancer, which correlate to its overexpressed condition. However, the mechanism behind its deregulated expression in the context of cancer has not been addressed before. In the present study we uncover an oncogenic function of CARM1 in the context of oral cancer, where it was found to be overexpressed. We also identify YY1 to be a positive regulator of CARM1 gene promoter, where silencing of YY1 in oral cancer cell line could lead to reduction in expression of CARM1. In this context, YY1 showed concomitant overexpression in oral cancer patient samples compared to adjacent normal tissue. Cell line based experiments as well as xenograft study revealed pro-neoplastic functions of YY1 in oral cancer. Transcriptomics analysis as well as qRT-PCR validation clearly indicated pro-proliferative, pro-angiogenic and pro-metastatic role of YY1 in oral cancer. We also show that YY1 is a substrate of CARM1 mediated arginine methylation, where the latter could coactivate YY1 mediated reporter gene activation in vivo. Taken together, CARM1 and YY1 were found to regulate each other in a positive feedback loop to facilitate oral cancer progression.

Haploinsufficient tumor suppressor Tip60 negatively regulates oncogenic Aurora B kinase.

The Aurora kinases represent a group of serine/threonine kinases which are crucial regulators of mitosis. Dysregulated Aurora kinase B (AurkB) expression, stemming from genomic amplification, increased gene transcription or overexpression of its allosteric activators, is capable of initiating and sustaining malignant phenotypes. Although AurkB level in cells is well-orchestrated, studies that relate to its stability or activity, independent of mitosis, are lacking. We report that AurkB undergoes acetylation in vitro by lysine acetyltransferases (KATs) belonging to different families, namely by p300 and Tip60. The haploinsufficient tumor suppressor Tip60 acetylates two highly conserved lysine residues within the kinase domain of AurkB which not only impinges the protein stability but also its kinase activity. These results signify a probable outcome on the increase in "overall activity" of AurkB upon Tip60 downregulation, as observed under cancerous conditions. The present work, therefore, uncovers an important functional interplay between AurkB and Tip60, frailty of which may be an initial event in carcinogenesis.

Unraveling the role of aurora A beyond centrosomes and spindle assembly: implications in muscle differentiation.

Aurora kinases are critical mitotic serine/threonine kinases and are often implicated in tumorigenesis. Recent studies of the interphase functions for aurora kinase (Aurk)A have considerably expanded our understanding of its role beyond mitosis. To identify the unknown targets of AurkA, we used peptide array-based screening and found E2F4 to be a novel substrate. Phosphorylation of E2F4 by AurkA at Ser75 regulates its DNA binding and subcellular localization. Because E2F4 plays an important role in skeletal muscle differentiation, we attempted to gain insight into E2F4 phosphorylation in this context. We observed that a block in E2F4 phosphorylation retained it better within the nucleus and inhibited muscle differentiation. RNA sequencing analysis revealed a perturbation of the gene network involved in the process of muscle differentiation and mitochondrial biogenesis. Collectively, our findings establish a novel role of AurkA in the process of skeletal muscle differentiation.-Dhanasekaran, K., Bose, A., Rao, V. J., Boopathi, R., Shankar, S. R., Rao, V. K., Swaminathan, A., Vasudevan, M., Taneja, R., Kundu, T. K. Unravelling the role of aurora A beyond centrosomes and spindle assembly: implications in muscle differentiation.

Establishment of quality function deployment with special reference to good manufacturing practice of Chandraprabha Vati.

CONTEXT: Quality function deployment (QFD) is a powerful tool for the translation of vague, imprecise customer requirements into clear, measurable technical requirements. AIMS: The objective of this article is twofold: (a) to propose a platform conceptual model for Chandraprabha Vati and (b) to present 10-step procedure to build QFD matrix. MATERIALS AND METHODS: The method deals with, first, preparing two conceptual models for Chandraprabha Vati for the sake of manufacturing unit. The survey study was carried out for two products for the selection of customer requirement. Then, with the help of survey study QFD's house of quality matrix was prepared which contained two products, i.e., classical product prepared by pharmacy of university and marketed product. High performance thin layer chromatography study was also carried out. STATISTICAL ANALYSIS USED: Principal component analysis (PCA) was applied to the data using unscrambler software. RESULTS: The results of QFD chart and PCA analysis were obtained from the two surveys. The first survey reveals that if proper care is taken during preparation on hardness and capping of Vati, then product goes toward zero defects. The second survey reveals that if proper care is taken during preparation on hardness, capping and sticking, then physically Vati goes toward zero defects. CONCLUSIONS: The 10-step procedure facilitates the process of reasoning and reduces the time spent for manufacturing with zero defect in product.

Association of serum testosterone levels and testicular volume in adult patients.

A retrospective observational study was undertaken to gain new insight into the relationship between total testicular volume and levels of serum testosterone, luteinising hormone, follicle-stimulating hormone, prolactin and clinical variables. A total of 312 men with sexual dysfunction or infertility were divided into groups A and B (156 each) on the basis of basal plasma testosterone ≤5 nmol/L of ≥12 nmol/L respectively. Group A was subclassified in A1 (primary hypogonadism) and A2 (secondary hypogonadism). There were significant differences in total testicular volume between group A (15.33 ± 11.94 ml) and group B (36.74 ± 6.9; p < .001) and also between subgroup A1 (11.07 ± 8.49 ml) and subgroup A2 (23.62 ± 13.04 ml; p < .001). Only 13.5% of patients in group B had a total testicular volume <30 ml. Differences in all studied parameters were found between group A and group B. There were no variations when comparing age, body mass index and testosterone in groups A1 and A2 . The use of total testicular volume and body mass index together for predicting testosterone levels yields a sensitivity and specificity of 85.3% and 86.5% respectively. Logistic regression analysis, univariate and multivariate models, using the measurement of total testicular volume resulted in a high capacity to predict testosterone levels.

Triterpenoid and Fatty Acid Contents from the Stem Bark of Cordia dichotoma (Forst f.).

AIM: To isolate and determine the chemical constituents of the stem bark of Cordia dichotoma (Forst f.), a plant used for medicinal purpose in folk medicine. MATERIALS AND METHODS: Petroleum ether extract of the stem bark was used for this study. Saponification process was performed to separate fatty acid and unsaponifiable matter. RESULTS: One triterpenoids, α-amyrin was isolated from the bark by using isocratic elution. The chemical compounds isolated, for the first time, were analyzed by GC/MS, IR, and UV. The chemical composition of the fatty acids methyl esters (FAMEs) in bark of Cordia dichotoma were also analyzed by gas chromatography-mass spectrometry. After methyl-esterification, 17 components were identified in the bark. The derivatization conditions were investigated in order to validate this method. CONCLUSION: The present analysis revealed that Cordia dichotoma stem bark contains 17 fatty acid. The principal themes of the review highlight the development and application of chromatographic techniques for the separation, isolation and detection of the compounds.