Liposomes for the treatment of prostate cancer therapy: A review.

One of the cancers that affect men, prostate cancer considerably raises mortality rates for males around the world. Patients with prostate cancer can have a localized or advanced form of the illness. Digital rectal examinations, prostate-specific antigen analyses, and prostate biopsies are all used to identify prostate cancer. The onset, development, and spread of cancer are all correlated with mutations in specific genes. Radical prostatectomy, ablative radiation, and active surveillance are all forms of treatment for localized prostate cancer. Androgen deprivation therapy (ADT), radiation, and chemotherapy are given to men who have metastatic prostate cancer or have experienced a relapse. When compared to traditional cancer chemotherapeutic methods, the liposome-based drug delivery technology offers less toxic, biodegradable, and biocompatible nanomedicine. Liposomes offer great advantages for use in nanomedicines by improving the sensitivity, specificity, and persistence of these anti-malignant cell agents in the body. Liposomal formulations are undergoing clinical trials of variety of cancers including prostate cancer. The present narrative review describes the composition and types of liposomes, its advantages, disadvantages, and the methods of preparation, research studies, clinical applications, drug repurposing and administration.

Utility of Epicardial Fat Thickness in Subclinical Hypothyroid Children to Determine Existence of Subclinical Atherosclerosis in Them.

Context: Adult studies have shown the association of subclinical hypothyroid (SCH) with various cardiovascular dysfunction, which indicates SCH may be a potentially modifiable risk factor of CV disease and mortality. However, there is still controversy about the association of cardiovascular dysfunction in children with SCH. Epicardial fat thickness (EFT) is a reliable and sensitive marker of cardiovascular risk and has become an emerging modality to predict CV risks. Aims: To measure the EFT in children with subclinical hypothyroidism and compare with healthy children. To find its correlation with subclinical atherosclerosis. To compare EFT between TPO positive and TPO negative subclinical hypothyroid patients. Materials and Methods: Children of subclinical hypothyroidism (TSH >5 mIU/ml with normal FT3, FT4, and age and sex matched control were included as per inclusion and exclusion criteria. Clinical data was collected from all study subjects. Thyroid function tests including FT3, FT4 and TSH, TPO antibody, fasting insulin, hsCRP, Lp(a), USG neck for carotid intima media thickness (CIMT), USG brachial artery for flow mediated dilation (FMD) and echocardiography for epicardial fat thickness (EFT) were done in all patients. Results: A total 42 number of SCH and 50 age and sex matched controls were recruited and screened for various parameters of subclinical atherosclerosis. EFT was significantly higher in the cases than in the controls (6.27 mm vs 4.54 mm) with P value < 0.001. Brachial FMD was significantly lower in cases than the cohort (4.5% vs 8.93%, P < 0.001). Difference in CIMT was not significant amongst the cases and controls. EFT failed to correlate with the level of TSH though it had significant positive correlation with hsCRP. The patients who were TPO positive, had higher fasting insulin, HOMAIR, hsCRP, Lp(a) than those who were TPO negative. Conclusion: Results of this study show the presence of subclinical atherosclerosis in children with SCH regardless of the aetiologies. The patients of Hashimoto thyroiditis had significantly high insulin resistance and inflammation than the SCH patients of other aetiologies.

Performance of Trichogramma japonicum under field conditions as a function of the factitious host species used for mass rearing.

Different factitious hosts were used to mass rear Trichogramma japonicum Ashmead in different parts of the globe because thorough details were lacking in both the laboratory and the field. The objective of this study was to compare, parasitoid, T. japonicum reared in different factitious hosts. Three commonly used factitious host eggs, Corcyra cephalonica (Stainton), Ephestia kuehniella Zeller and Sitotroga cerealella Olivier were tested under laboratory conditions and then in the field over a yellow stem borer, Scirpophaga incertulus (Walker) of rice. The highest parasitism by T. japonicum was observed on E. kuehniella eggs. The parasitoid's highest emergence (88.99%) was observed on S. cerealella eggs at 24 h exposure, whereas at 48 h it was on E. kuehniella eggs (94.66%). Trichogramma japonicum females that emerged from E. kuehniella eggs were significantly long-lived. The days of oviposition by hosts and the host species were significant individually, but not their interaction. Higher proportions of flying T. japonicum were observed when reared on E. kuehniella and C. cephalonica eggs. Field results showed that T. japonicum mass-reared on E. kuehniella showed higher parasitism of its natural host, S. incertulus eggs. Hence, by considering these biological characteristics and field results, E. kuehniella could be leveraged for the mass rearing of quality parasitoids of T. japonicum in India, the Asian continent and beyond.

Depletion of TrkB Receptors From Adult Serotonergic Neurons Increases Brain Serotonin Levels, Enhances Energy Metabolism and Impairs Learning and Memory.

Neurotrophin brain-derived neurotrophic factor (BDNF) and neurotransmitter serotonin (5-HT) regulate each other and have been implicated in several neuronal mechanisms, including neuroplasticity. We have investigated the effects of BDNF on serotonergic neurons by deleting BDNF receptor TrkB from serotonergic neurons in the adult brain. The transgenic mice show increased 5-HT and Tph2 levels with abnormal behavioral phenotype. In spite of increased food intake, the transgenic mice are significantly leaner than their wildtype littermates, which may be due to increased metabolic activity. Consistent with increased 5-HT, the proliferation of hippocampal progenitors is significantly increased, however, long-term survival of newborn cells is unchanged. Our data indicates that BDNF-TrkB signaling regulates the functional phenotype of 5-HT neurons with long-term behavioral consequences.

Antidepressant drugs act by directly binding to TRKB neurotrophin receptors.

It is unclear how binding of antidepressant drugs to their targets gives rise to the clinical antidepressant effect. We discovered that the transmembrane domain of tyrosine kinase receptor 2 (TRKB), the brain-derived neurotrophic factor (BDNF) receptor that promotes neuronal plasticity and antidepressant responses, has a cholesterol-sensing function that mediates synaptic effects of cholesterol. We then found that both typical and fast-acting antidepressants directly bind to TRKB, thereby facilitating synaptic localization of TRKB and its activation by BDNF. Extensive computational approaches including atomistic molecular dynamics simulations revealed a binding site at the transmembrane region of TRKB dimers. Mutation of the TRKB antidepressant-binding motif impaired cellular, behavioral, and plasticity-promoting responses to antidepressants in vitro and in vivo. We suggest that binding to TRKB and allosteric facilitation of BDNF signaling is the common mechanism for antidepressant action, which may explain why typical antidepressants act slowly and how molecular effects of antidepressants are translated into clinical mood recovery.

In vitro anticancer activity of Eclipta alba whole plant extract on colon cancer cell HCT-116.

BACKGROUNDS: Colon cancer is the third most deadly and one of the most diagnosed diseases in the world. Although routine screening and early detection during last decades has improved the survival, colon cancer still claims hundreds of thousands lives each year worldwide. Surgery and chemotherapy is mainstay of current treatment, nevertheless toxicity associated with this treatment underscores the urgency of demand of a better therapeutics. Close to 50% of current chemotherapeutic drugs are direct or indirect descendants compounds isolated from medicinal plants, which indicate plants are great potential sources of novel therapeutics. In our literature review we found Eclipta alba to posses many pharmacological activities, including those with anticancer potentials. However, no study on anticancer activity of this kind has been reported. METHODS: Phytochemicals were extracted by maceration method from shade dried whole plant of Eclipta alba using methanol as a solvent. The anticancer effect of extract was investigated on various cancer cell lines like human colorectal carcinoma (HCT-116), human prostate cancer (PC-3), Michigan cancer foundation-breast cancer (MCF-7) and renal cell carcinoma (RCC-45). We have also studied the effects on normal human embryonic lung fibroblast cell (WI-38) using MTT (methyl thiazoldiphenyltetrazolium bromide) assay, clonogenic (colony formation) and migration assay. Finally obtained results were analyzed using ANNOVA and Dunnett's test. RESULTS: Results obtained from MTT assay revealed that the methanolic extract of Eclipta alba carried significant (p < 0.005) specificity against HCT-116 cells as compared to the other cancer cells. This extract also showed minimal or nontoxicity to WI-38 cells. Migration as well as clonogenic assays also confirmed the anticancer potential of the extract against HCT-116 cells. CONCLUSION: This is a unique finding of its kind because the specific anticancer effect with minimal toxicity on normal cells has not been reported on Eclipta alba extract. Finally this finding opens up a great possibility to develop a novel antitumor drug candidate against deadly colon cancer in the future.

Dissipation of chlorantraniliprole in contrasting soils and its effect on soil microbes and enzymes.

An experiment was set up to determine the rate of dissipation of chlorantraniliprole (CTP) from two soils with contrasting properties. The other objective of the study was to find out the effect of CTP on soil microorganisms (population, microbial biomass carbon and soil enzymes) under controlled environment. CTP residues when applied at recommended dose ((RD) (at 40 g a.i./ha)) could not be recovered either from alluvial soil or red soil at 60 days post application of CTP in a microcosm study. Higher clay content led to higher half-life in alluvial soil compared to red soil. CTP could not be recovered from RD treatment at 30 days after pesticide application under controlled environment. Faster dissipation of CTP was observed in rice rhizosphere soil with 23.89 and 34.65 days dissipation half-lives for RD and double the recommended dose (DRD) treatments, respectively. Different doses of chlorantraniliprole did not have considerable negative effect on actinomycetes, fungi, biological nitrogen fixers and phospahte solubilising bacteria except the bacteria population. Among the treatments, DRD recorded the lowest activity of dehyrodeganse, fluoresein diacetate hydrolase, acid and alkaline phosphatases followed by RD treatment. Microbial biomass carbon, ß -glycosidase and urease did not vary significantly among the different doses of CTP. In general, RD did not have negative effcts on soil microbes. Hence, CTP can be recommeded in rice pest managment maintaining existing soil microbes and soil enzymes activity.

Neurotrophin receptor Ntrk2b function in the maintenance of dopamine and serotonin neurons in zebrafish.

Neurotrophins and their receptors have highly conserved evolutionary lineage in vertebrates including zebrafish. The NTRK2 receptor has two isoforms in zebrafish, Ntrk2a and Ntrk2b. The spatio-temporal expression pattern of bdnf and ntrk2b in the zebrafish brain was studied using in situ hybridization. The robust and corresponding expression pattern of ntrk2b to bdnf suggests that ntrk2b is the key receptor for bdnf in the zebrafish brain, unlike its duplicate isoform ntrk2a. To study ntrk2b function, two different genetic strategies, the TILLING mutant and morpholino oligonucleotides (MO), were used. Specific subsets of the dopaminergic and serotonergic neuronal populations were affected in the mutants and morphants. The mutant showed anxiety- like behavior both in larval and adult stages. Our results consistently indicate that BDNF/NTRK2 signaling has a significant role in the development and maintenance of aminergic neuronal populations. Therefore, the ntrk2b-deficient zebrafish is well suited to study mechanisms relevant for psychiatric disorders attributed to a dysfunctional monoaminergic system.

Culturing primary neurons from rat hippocampus and cortex.

Primary neurons from rodent brain hippocampus and cortex have served as important tools in biomedical research over the years. However, protocols for the preparation of primary neurons vary, which often lead to conflicting results. This report provides a robust and reliable protocol for the production of primary neuronal cultures from the cortex and hippocampus with minimal contribution of non-neuronal cells. The neurons were grown in serum-free media and maintained for several weeks without any additional feeder cells. The neuronal cultures maintained according to this protocol differentiate and by 3 weeks develop extensive axonal and dendritic branching. The cultures produced by this method show excellent reproducibility and can be used for histological, molecular and biochemical methods.

A review of concurrent infections of malaria and dengue in Asia

Concurrent infections of malaria and dengue are when both of these mosquito-borne diseases occur simultaneously in an individual. In this review, reported cases with these co-infections in Asia are discussed. The focus is on the overlapping clinical presentations and the difficulties encountered in differential diagnosis. Also, cases reported in some special conditions, viz., pregnancy, foetal infections, and co-infections with one or more other infectious agents are highlighted. Due to similar clinical presentations of malaria and dengue, these co-infections may give rise to an incorrect diagnosis. Moreover, the treatment regimens for these co-infections are not the same as those for mono-infections. Hence, a delay in implementing the appropriate treatment regimen for these concurrent infections due to poor diagnosis can be fatal. The present review is intended to increase awareness about the clinical significance and the importance of these co-infections among clinicians, public health workers and health authorities in the Asian region. Though malaria-dengue concurrent infections are seldom reported from the Asian region, it is probably increasing particularly in the countries known to be endemic for both of the above diseases. A compulsory reporting of the incidences of malaria-dengue concurrent infections is recommended.

Role of mobile phone technology in health education in Asian and African countries: a systematic review.

The objective of this systematic review was to explore the role of mobile phone technologies in delivering health education programs in Asian and African countries. The search engine used was Pubmed during 2008-2011. Randomised controlled trials or controlled studies that improved health outcomes through delivery of health educational interventions using cell phone or text messaging were included in the review. Results showed studies from six Asian and African countries including Philippines, China, Kenya, South Korea, Taiwan and India. Mobile phone technology has shown to improve health outcomes for chronic disease conditions such as diabetes, heart disease and hypertension. Additional conditions include obesity and cardiopulmonary resuscitation guidance. Other studies have shown improvement in self management of breast cancer and post-hospitalisation HIV and pharmaceutical care. Overall results of the present review showed that mobile phone technologies can be a possible solution to improve healthcare outcome.

Validation of assay indicating method development of meloxicam in bulk and some of its tablet dosage forms by RP-HPLC.

A novel, simple and economic reverse phase high performance liquid chromatography (RP-HPLC) method has been developed for the quantification of Meloxicam in bulk and tablet dosage form with greater precision and accuracy. Separation was achieved on Develosil ODS HG-5 RP C18, (15 cm × 4.6 mm i.d. 5 µm) column in isocratic mode with mobile phase consisting of acetonitrile: phosphate buffer(pH 3.4) (60:40) with a flow rate of 1 mL/min. The detection was carried out at 268 nm. The retention time of Meloxicam was found to be 2.09 min. The method was validated as per ICH guidelines. Linearity was established for Meloxicam in the range 20 - 120 µg/ml with R(2) value 0.996. The percentage recovery of Meloxicam was found to be in the range 99.99-100.46%. The high recovery and low relative standard deviation confirm the suitability of the proposed method for the estimation of the drug in bulk and tablet dosage forms. Validation studies demonstrated that the proposed RP-HPLC method is simple, specific, rapid, reliable and reproducible for the determination of Meloxicam for Quality Control level.