Liposome encapsulated anticancer drugs on autophagy in cancer cells - Current and future perspective.

Autophagy act as a double-edged sword in cancer with both tumor promoting and inhibiting roles. Under normal conditions of autophagy, the damaged cell organelles and other debris degrade inside the lysosome to provide energy and macromolecular precursors. However, enhanced autophagy can lead to apoptosis and programmed cell death highlighting its significance in cancer therapy. Liposome-based drug delivery systems for treating cancer patients have significant advantages over their non-formulated or free drug counterparts which could be effectively used to manipulate autophagy pathway in cancer patients. In the current review, drug uptake by the cells and its role in autophagy-mediated cancer cell death are discussed. Besides, the challenges and translational difficulties associated with the use of liposome-based chemotherapeutic drugs in clinical trials and in biomedical applications are also discussed.

Decision Support System and Web-Application Using Supervised Machine Learning Algorithms for Easy Cancer Classifications.

Using a decision support system (DSS) that classifies various cancers provides support to the clinicians/researchers to make better decisions that can aid in early cancer diagnosis, thereby reducing chances of incorrect disease diagnosis. Thus, this work aimed at designing a classification model that can predict accurately for 5 different cancer types comprising of 20 cancer exomes, using the mutations identified from whole exome cancer analysis. Initially, a basic model was designed using supervised machine learning classification algorithms such as K-nearest neighbor (KNN), support vector machine (SVM), decision tree, naïve bayes and random forest (RF), among which decision tree and random forest performed better in terms of preliminary model accuracy. However, output predictions were incorrect due to less training scores. Thus, 16 essential features were then selected for model improvement using 2 approaches. All imbalanced datasets were balanced using SMOTE. In the first approach, all features from 20 cancer exome datasets were trained and models were designed using decision tree and random forest. Balanced datasets for decision tree model showed an accuracy of 77%, while with the RF model, the accuracy improved to 82% where all 5 cancer types were predicted correctly. Area under the curve for RF model was closer to 1, than decision tree model. In the second approach, all 15 datasets were trained, while 5 were tested. However, only 2 cancer types were predicted correctly. To cross validate RF model, Matthew's correlation co-efficient (MCC) test was performed. For method 1, the MCC test and MCC cross validation was found to be 0.7796 and 0.9356 respectively. Likewise, for second approach, MCC was observed to be 0.9365, corroborating the accuracy of the designed model. The model was successfully deployed using Streamlit as a web application for easy use. This study presents insights for allowing easy cancer classifications.

MutaXome: A Novel Database for Identified Somatic Variations of In silico Analyzed Cancer Exome Datasets.

Advancements in the field of cancer research have enabled researchers and clinicians to access a massive amount of data to aid cancer patients and to add to the existing knowledge of research. However, despite the existence of reliable sources for extricating this data, it remains a challenge to accurately comprehend and draw conclusions based on the entirety of available information. Therefore, the current study aimed to design and develop a database for the identified variants of 5 different cancer types using 20 different cancer exomes. The exome data were retrieved from NCBI SRA and an NGS data clean-up protocol was implemented to obtain the best quality reads. The reads which passed the quality checks were then used for calling the variants which were then processed and filtered. This data was used to normalize and the normalized data generated was used for developing the database. MutaXome, which stands for mutations in cancer exome was designed in SQL, with the front end in bootstrap and HTML, and backend in PHP. The normalized data containing the variants inclusive of Single Nucleotide Polymorphisms (SNPs), were added into MutaXome, which contains detailed information regarding each type of identified variant. This database, available online via http://www.vidyalab.rf.gd/, serves as a knowledge base for cancer exome variations and holds much potential for enriching it by linking it to a decision support system as prospective studies.

Autophagy and cancer: Can tetrandrine be a potent anticancer drug in the near future?

Autophagy is an essential catabolic process in mammalian cells to maintain cellular integrity and viability by degrading the old and damaged cell organelles and other contents with the help of lysosomes. Deregulation in autophagy can be one of the major contributors leading to the continuous cell proliferation and development of tumors. Tetrandrine, a bisbenzylisoquinoline alkaloid known to have potent bioactivities such as anticancer, antimicrobial, anti-inflammatory, antidiabetic, antioxidant, immunosuppressive, cardiovascular, and calcium channel blocking effects. The present review evaluated the effectiveness of tetrandrine in targeting key proteins in the autophagy pathway to induce anticancer effect based on the available literature. An attempt is also made to understand the influence of tetrandrine in regulating autophagy by mTOR dependant and mTOR-independent pathways. In addition, the review also highlights the limitations involved and future perspectives in developing tetrandrine as a chemotherapeutic drug to treat cancer.

ABO phenotype and SARS-CoV-2 infection: Is there any correlation?

COVID-19 is the currently evolving viral disease worldwide. It mainly targets the respiratory organs, tissues and causes illness. A plethora of studies has been performing to bring proper treatment and prevent people from the infection. Likewise, susceptibility to some infectious diseases has been associated with blood group phenotypes. The co-relationship of blood group with the occurrence of SARS-CoV-2 infection and death has been examined in numerous studies. This review explained the described studies regarding the correlation of blood group and the other essential factors with COVID-19.

Molecular Docking and Interaction Studies of Identified Abscisic Acid Receptors in Oryza sativa: An In-Silico Perspective on Comprehending Stress Tolerance Mechanisms.

Background: Abiotic stresses affect plants in several ways and as such, phytohormones such as abscisic acid (ABA) play an important role in conferring tolerance towards these stresses. Hence, to comprehend the role of ABA and its interaction with receptors of the plants, a thorough investigation is essential. Aim: The current study aimed to identify the ABA receptors in Oryza sativa, to find the receptor that binds best with ABA and to examine the mutations present to help predict better binding of the receptors with ABA. Methods: Protein sequences of twelve PYL (Pyrabactin resistance 1) and seven PP2C (type 2C protein phosphatase) receptors were retrieved from the Rice Annotation Project database and their 3D structures were predicted using RaptorX. Protein-ligand molecular docking studies between PYL and ABA were performed using AutoDock 1.5.6, followed by 100ns molecular dynamic simulation studies using Desmond to determine the acceptable conformational changes after docking via root mean square deviation RMSD plot analysis. Protein-protein docking was then carried out in three sets: PYL-PP2Cs, PYL-ABA-PP2C and PYL(mut)-ABA-PP2C to scrutinize changes in structural conformations and binding energies between complexes. The amino acids of interest were mapped at their respective genomic coordinates using SNP-seek database to ascertain if there were any naturally occurring single nucleotide polymorphisms (SNPs) responsible for triggering rice PYLs mutations. Results: Initial protein-ligand docking studies revealed good binding between the complexes, wherein PYL6-ABA complex showed the best energy of -8.15 kcal/mol. The 100ns simulation studies revealed changes in the RMSD values after docking, indicating acceptable conformational changes. Furthermore, mutagenesis study performed at specific PYL-ABA interacting residues followed by downstream PYL(mut)-ABA-PP2C protein-protein docking results after induction of mutations demonstrated binding energy of -8.17 kcal/mol for PP2C79-PYL11-ABA complex. No naturally occurring SNPs that were responsible for triggering rice PYL mutations were identified when specific amino acid coordinates were mapped at respective genomic coordinates. Conclusion: Thus, the present study provides valuable insights on the interactions of ABA receptors in rice and induced mutations in PYL11 that can enhance the downstream interaction with PP2C.

Aleurothrixus trachoides (Back) can transmit begomovirus from Duranta to potato, tomato and bell pepper.

Solanum whitefly, Aleurothrixus trachoides (Back). (Hemiptera: Aleyrodidae) was considered as a non-virus vector by European and Mediterranean Plant Protection Organization (EPPO) reports. However, in the present study it was found to transmit Duranta leaf curl virus (DLCV) to tomato, bell pepper and potato. A. trachoides infested field samples of Duranta sp (100%) and tomato (20%) tested positive for begomovirus by PCR using begomovirus degenerate primers and primers specific to Tomato leaf curl New Delhi virus showing amplicon of 520 bp and 2.7 Kb respectively. The DNA samples of A. trachoides collected from virus positive duranta and tomato plants also tested positive for the virus. Virulent whiteflies from duranta could successfully transmit DLCV to bell pepper (26%) and tomato (13 %) plants as confirmed by Rolling Circle Amplification. The rate of virus transmission by A. trachoides from DLCV inoculated tomato to bell pepper and tomato to potato was 100% and tomato to tomato was 80%. The results suggest whitefly A. trachoides as the vector for DLCVand to the best of our knowledge, this is the first report for A. trachoides as vector of begomovirus. These findings suggest need for reconsideration of A. trachoides as a virus-vector. This will have great impact on solanaceous vegetable cultivation in India and other parts of the world.

Tetrandrine isolated from Cyclea peltata induces cytotoxicity and apoptosis through ROS and caspase pathways in breast and pancreatic cancer cells.

Tetrandrine is a bisbenzylisoquinoline alkaloid known to exhibit anticancer activity against different cancers. In the present study, the cytotoxic effect of tetrandrine isolated from Cyclea peltata on pancreatic (PANC-1) and breast (MDA-MB-231) cancer cells was evaluated in vitro with an attempt to understand the role of tetrandrine on the generation of reactive oxygen species (ROS) and caspase activation. Results demonstrate the dose- and time-dependant cytotoxic effect of tetradrine on both MDA-MB-231 and PANC-1 cells with IC50 values ranging between 51 and 54 µM and 22 and 27 µM for 24 h and 48 h of incubation respectively. In addition, treatment of MDA-MB-231 and PANC-1 cells with tetrandrine showed the shrunken cytoplasm and damaged cell membrane in a dose- and time-dependant manner under the microscope. Also, tetrandrine treatment revealed an elevated levels of reactive oxygen species and increased activities of caspase-8, -9 and -3 confirming the apoptosis of cells through both extrinsic death receptor and intrinsic caspase activation. Therefore, the present study suggests the apoptosis of cells with the activation of caspase pathways mainly intrinsic pathway as a downstream event of tetrandrine-induced ROS generation. Hence, reactive oxygen species-mediated caspase activation pathway may be potentially targeted with the use of tetrandrine to treat breast and pancreatic cancers.

Genetic homogeneity in South American tomato pinworm, Tuta absoluta: a new invasive pest to oriental region.

South American tomato leaf miner, Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae), is an important invasive pest of Tomato which invaded India and Nepal in 2014 and 2016, respectively. In the present study, samples from five localities of India and one from Nepal were used for the investigation of genetic diversity of T. absoluta by employing a fragment in the mtDNA gene-encoding cytochrome oxidase I (COI). Based on the partial COI gene, high genetic homogeneity was detected in T. absoluta populations of India and Nepal with rest of the world. Less nucleotide diversity (π 0.00137) was also detected in the populations of T. absoluta from different countries. This is first attempt to analyze molecular data for this new invasive species from India and Nepal.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study.

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

Expression of an insecticidal fern protein in cotton protects against whitefly.

Whitefly (Bemisia tabaci) damages field crops by sucking sap and transmitting viral diseases. None of the insecticidal proteins used in genetically modified (GM) crop plants to date are effective against whitefly. We report the identification of a protein (Tma12) from an edible fern, Tectaria macrodonta (Fee) C. Chr., that is insecticidal to whitefly (median lethal concentration = 1.49 µg/ml in in vitro feeding assays) and interferes with its life cycle at sublethal doses. Transgenic cotton lines that express Tma12 at ∼0.01% of total soluble leaf protein were resistant to whitefly infestation in contained field trials, with no detectable yield penalty. The transgenic cotton lines were also protected from whitefly-borne cotton leaf curl viral disease. Rats fed Tma12 showed no detectable histological or biochemical changes, and this, together with the predicted absence of allergenic domains in Tma12, indicates that Tma12 might be well suited for deployment in GM crops to control whitefly and the viruses it carries.

Tetrandrine--A molecule of wide bioactivity.

Stephania tetrandra and other related species of Menispermaceae form the major source of the bisbenzylisoquinoline alkaloid - tetrandrine. The plant is extensively referenced in the Chinese Pharmacopoeia for its use in the Chinese medicinal system as an analgesic and diuretic agent and also in the treatment of hypertension and various other ailments, including asthma, tuberculosis, dysentery, hyperglycemia, malaria, cancer and fever. Tetrandrine, well-known to act as a calcium channel blocker, has been tested in clinical trials and found effective against silicosis, hypertension, inflammation and lung cancer without any toxicity. Recently, the efficacy of tetrandrine was tested against Mycobaterium tuberculosis, Candida albicans, Plasmodium falciparum and Ebola virus. Tetrandrine's pharmacological property has been proved to be through its action on different signalling pathways like reactive oxygen species, enhanced autophagic flux, reversal of multi drug resistance, caspase pathway, cell cycle arrest and by modification of calcium channels. The present review summarises current knowledge on the synthesis, distribution, extraction, structural elucidation, pharmacological properties and the mechanism of action of tetrandrine. Future perspectives in the clinical use of tetrandrine as a drug are also considered.

Simultaneous expression of regulatory genes associated with specific drought-adaptive traits improves drought adaptation in peanut.

Adaptation of crops to drought-prone rain-fed conditions can be achieved by improving plant traits such as efficient water mining (by superior root characters) and cellular-level tolerance mechanisms. Pyramiding these drought-adaptive traits by simultaneous expression of genes regulating drought-adaptive mechanisms has phenomenal relevance in improving stress tolerance. In this study, we provide evidence that peanut transgenic plants expressing Alfalfa zinc finger 1 (Alfin1), a root growth-associated transcription factor gene, Pennisetum glaucum heat-shock factor (PgHSF4) and Pea DNA helicase (PDH45) involved in protein turnover and protection showed improved tolerance, higher growth and productivity under drought stress conditions. Stable integration of all the transgenes was noticed in transgenic lines. The transgenic lines showed higher root growth, cooler crop canopy air temperature difference (less CCATD) and higher relative water content (RWC) under drought stress. Low proline levels in transgenic lines substantiate the maintenance of higher water status. The survival and recovery of transgenic lines was significantly higher under gradual moisture stress conditions with higher biomass. Transgenic lines also showed significant tolerance to ethrel-induced senescence and methyl viologen-induced oxidative stress. Several stress-responsive genes such as heat-shock proteins (HSPs), RING box protein-1 (RBX1), Aldose reductase, late embryogenesis abundant-5 (LEA5) and proline-rich protein-2 (PRP2), a gene involved in root growth, showed enhanced expression under stress in transgenic lines. Thus, the simultaneous expression of regulatory genes contributing for drought-adaptive traits can improve crop adaptation and productivity under water-limited conditions.

Genotoxic and cytotoxic effects of X-ray on buccal epithelial cells following panoramic radiography: A pediatric study.

BACKGROUND: Ionizing radiation is a potent mutagenic agent capable of inducing both mutation and chromosomal aberrations. Non-lethal doses of ionizing radiation may induce genomic instability favoring carcinogenesis. In spite of their mutagenic potential, this kind of radiation is an important tool for diagnosis of the disease and is used in medical and dental practice. It has been believed that the number of micronucleus and increased frequency of other nuclear alterations, including karyorrhexis, condensed chromatin and pyknosis, are related to the increasing effects of carcinogens. Many approaches and techniques have been developed for the monitoring of human populations exposed to various mutagens, but the analysis of micronuclei (MN) has become a standard approach for the assessment of chromosomal damage in human populations. AIM: To assess the effects of radiation exposure from panoramic radiography on the buccal epithelial cells (BECs) of pediatric patients. MATERIALS AND METHODS: The study included 20 pediatric patients who had to undergo panoramic radiography for further dental treatment. Exfoliated BECs were obtained and examined immediately before and 10 days after radiation exposure. The cells were stained using rapid Papanicolaou (PAP) kit. Evaluation for MN and nuclear alterations was carried out by an oral pathologist and data were statistically analyzed using the "t" test. RESULTS: The mean number of MN in the BECs before exposure of pediatric patients to panoramic radiography was 4.25 and after exposure was 4.40. This difference was not found to be statistically significant (P < 0.0001). However, the mean nuclear alterations of 8.70 and 15.75 before and after exposure were statistically significant (P < 0.0001). CONCLUSION: Panoramic radiographs can induce cytotoxicity but not genotoxic effects in buccal mucosal cells. Hence, dental radiographs should be prescribed only when deemed indispensable.

Whitefly genome expression reveals host-symbiont interaction in amino acid biosynthesis.

BACKGROUND: Whitefly (Bemisia tabaci) complex is a serious insect pest of several crop plants worldwide. It comprises several morphologically indistinguishable species, however very little is known about their genetic divergence and biosynthetic pathways. In the present study, we performed transcriptome sequencing of Asia 1 species of B. tabaci complex and analyzed the interaction of host-symbiont genes in amino acid biosynthetic pathways. METHODOLOGY/PRINCIPAL FINDINGS: We obtained about 83 million reads using Illumina sequencing that assembled into 72716 unitigs. A total of 21129 unitigs were annotated at stringent parameters. Annotated unitigs were mapped to 52847 gene ontology (GO) terms and 131 Kyoto encyclopedia of genes and genomes (KEGG) pathways. Expression analysis of the genes involved in amino acid biosynthesis pathways revealed the complementation between whitefly and its symbiont partner Candidatus Portiera aleyrodidarum. Most of the non-essential amino acids and intermediates of essential amino acid pathways were supplied by the host insect to its symbiont. The symbiont expressed the pathways for the essential amino acids arginine, threonine and tryptophan and the immediate precursors of valine, leucine, isoleucine and phenyl-alanine. High level expression of the amino acid transporters in the whitefly suggested the molecular mechanisms for the exchange of amino acids between the host and the symbiont. CONCLUSIONS/SIGNIFICANCE: Our study provides a comprehensive transcriptome data for Asia 1 species of B. tabaci complex that focusses light on integration of host and symbiont genes in amino acid biosynthesis pathways.

Oxidative status in the macula densa modulates tubuloglomerular feedback responsiveness in angiotensin II-induced hypertension.

AIM: Tubuloglomerular feedback (TGF) is an important mechanism in control of signal nephron glomerular filtration rate. The oxidative stress in the macula densa, primarily determined by the interactions between nitric oxide (NO) and superoxide (O2-), is essential in maintaining the TGF responsiveness. However, few studies examining the interactions between and amount of NO and O2- generated by the macula densa during normal and hypertensive states. METHODS: In this study, we used isolated perfused juxtaglomerular apparatus to directly measure the amount and also studied the interactions between NO and O2- in macula densa in both physiological and slow pressor Angiotensin II (Ang II)-induced hypertensive mice. RESULTS: We found that slow pressor Ang II at a dose of 600 ng kg(-1) min(-1) for two weeks increased mean arterial pressure by 26.1 ± 5.7 mmHg. TGF response increased from 3.4 ± 0.2 µm in control to 5.2 ± 0.2 µm in hypertensive mice. We first measured O2- generation by the macula densa and found it was undetectable in control mice. However, O2- generation by the macula densa increased to 21.4 ± 2.5 unit min(-1) in Ang II-induced hypertensive mice. We then measured NO generation and found that NO generation by the macula densa was 138.5 ± 9.3 unit min(-1) in control mice. The NO was undetectable in the macula densa in hypertensive mice infused with Ang II. CONCLUSIONS: Under physiological conditions, TGF response is mainly controlled by the NO generated in the macula densa; in Ang II induced hypertension, the TGF response is mainly controlled by the O2- generated by the macula densa.

Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors.

A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.

Gamma sensitivity of forest plants of Western Ghats.

Seeds of Artocarpus hirsutus Lam., Garcinia xanthochymus Hook., Saraca asoca Roxb., Rourea minor Gaertn., Pterocarpus marsupium Roxb., Terminalia chebula Retz., Aporusa lindleyana (Wt.) bail., Holoptelea integrifolia Roxb. and Oroxylum indicum (L.) Vent. were collected from different regions of Western Ghats and exposed to different doses of gamma radiation using Co-60 source. The effect of irradiation was examined on germination, growth and vigor parameters. Decrease in the germination and growth attributes with increased dose was observed in A. hirsutus, G. xanthochymus and S. asoca and thus indicating sensitivity of these plants to radiation. In contrast, enhancement in the germination (percentage), vigor and generation of leaves was observed for P. marsupium, T. chebula, H. integrifolia and O. indicum. These plants were classified as radiation tolerant because of the ability of their seedlings to successfully establish under radiation stress. R. minor and A. lindleyana were able to maintain viability up to 100 Gy dose, however, any further increase in the dose found to have negative effect.

Pachyonychia congenita tarda: A rare case report.

Pachyonychia congenita is a rare, but well-characterized autosomal dominant disorder of keratinization. It usually begins within the first few months of life. Here, we are presenting a rare case, which started at the age of 10 years of life and is known as pachyonychia congenita tarda. The case is being reported for its rarer occurrence as the patient had oral leukokeratosis and angular cheilosis present in the same type of the syndrome (Jadassohn-Lewandowsky syndrome), which is still uncommon.

Effect of an herb root extract, herbal dentifrice and synthetic dentifrice on human salivary amylase.

BACKGROUND: Salivary amylase is an enzyme, which plays a vital role in formation of dental plaque. It has the ability to bind on the bacterial surfaces and to hydrolyze starch, giving rise to products that are transformed into acids leading to dental caries. Suppression of salivary amylase activity can lead to decrease in risk of dental caries and plaque associated periodontal diseases. The aim of this study was to evaluate the effect of an herb, Spilanthes calva (in form of a test dentifrice) on human salivary amylase activity and to compare it with other dentifrices. MATERIALS AND METHODS: A total of 80 subjects of age 18-35 years were randomly selected and divided equally into 4 groups. Group 1 subjects were assigned to use Test Dentifrice (with S. calva root extract), while Group 2, Group 3, and Group 4 subjects were assigned to use Herbal Dentifrice (Arodent(™)), Synthetic Dentifrice (Colgate(®)), and Control Dentifrice respectively. Salivary amylase activity was determined by Bernfeld method in each group, before and after using the given dentifrices. RESULTS: Maximum inhibition of salivary amylase activity was found in the group using test dentifrice as compared to others. CONCLUSION: The present study indicates that, the root extract of S. calva possess significant inhibitory activity for salivary amylase. Use of S. calva root extract will provide a wider protection against different pathogenic oral microflora. Use of this extract singly or in combination is strongly recommended in the dentifrice formulations.