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Objective: To manage the increasing burden of skin cancer cases globally and to replace conventional invasive treatments and their side effects, the present study is aimed to develop a transfersomal herbal gel of Green Tea Catechins (GTC) extracted from indigenous green tea and evaluate it for in vivo management of skin cancer in an experimental animal model. Methods: GTC-loaded transfersomes (GTCTF) were prepared by the thin-film hydration method. After optimizing the GTCTFs using the Box-Behnken design, they were characterized for zeta potential, structure, in vitro drug release, and in vitro skin permeation. Carbopol 940 gel was developed for the topical delivery of GTCTF and characterized for pH, viscosity, spreadability and in vitro skin permeation. In vitro MTT assay and in vivo chemopreventive and anticancer efficacy of the GTCTF gel were evaluated in mice. Results: The GTCTF has shown a particle size of 151.4±1.9 nm, entrapment efficiency of 68.25±0.06 %, and drug loading of 10.41±0.02 %. The in vitro MTT assay in B16F10 melanoma cell lines showed promising anticancer efficacy of the GTCTF. GTCTF gel was found suitable for topical delivery with favorable pH, viscosity, spreadability, and permeability and effective in preventing and curing skin cancer in mice, with a significant reduction of tissue biochemical parameters like TNF-α, IL-1β, and IL-6. Conclusion: Collectively, successful prevention and curing of the induced skin cancer in the experimental animal model by the GTCTF gel have established a novel herbal nanomedicine approach for the management of skin cancer.

Tuberculosis (TB) patients present dysregulated immunity, iron metabolism and anaemia of inflammation. In this study, circulatory cytokines, trace metals, and iron-related proteins (hepcidin, ferroportin, transferrin, DMT1, Nramp1, ferritin, ceruloplasmin, hemojuvelin, aconitase, transferring receptor) were monitored in case (active tuberculosis patients: ATB) and control (non-tuberculosis: NTB and healthy) study populations (n=72, male, 42.94 mean age (16-83)). Using serum elemental and cytokine levels, a partial least square discriminate analysis model (PLS-DA) was built and variables with a VIP score of >0.6 were selected as important markers. A biosignature of IL-13, IL-12(p70), IFN-γ, IL-10, IL-5, IL-18, IL-4, Selenium, and Aluminium clustered ATB away from controls. Interestingly, low iron and selenium levels, while high copper and aluminum levels were observed in ATB subjects. All the important serum cytokines were positively correlated in ATB subjects. A low abundance of transferrin, ferroportin, and hemojuvelin, while higher ferritin and ceruloplasmin levels explained an altered iron metabolism in ATB subjects which partially resolved upon completion of treatment. Further, the identified biosignature in TB patients, that explained anemia of inflammation, along with perturbed iron homeostasis could be useful targets for the development of host-directed adjunct therapeutics.

Objectives: In this study, systematic pharmacognostic study and preliminary phytochemical screening of the bark of Cascabela thevetia L. were carried out. Methods: The selected plant part was collected, processed and stored in an airtight container. From the bark different pharmacognostic studies like macroscopic and microscopic evaluation, physicochemical parameters, fluorescence analysis were done. Powdered bark was successively extracted by petroleum ether, chloroform, ethyl acetate, and methanol using a Soxhlet apparatus and finally macerated with the hydro-alcoholic solvent system (30:70). The preliminary phytochemical analysis and thin layer chromatography of the extracts were done to find the nature and number of the different phytoconstituents present. Results: Transverse microscopy reveals the presence of crystal oxalate, cork cell, starch granules, vascular bundle, phloem fiber, parenchyma cells, and collenchyma cells. Powder microscopy also showed the presence of cork cell, fiber and calcium oxalate crystal. Results obtained in different physicochemical analysis like total ash, acid insoluble ash, water soluble ash, alcohol-soluble extractive, water-soluble extractive, and moisture content were 8.67%, 0.83%, 5.33%, 4.53%, 12.27%, and 7.83% respectively. Phytochemical analysis showed the presence of alkaloid, flavonoid, triterpenoid, phytosterol, tannin, saponin, anthraquinone, carbohydrate and fatty acid in the different extracts. TLC (Thin Layer Chromatography) study revealed 4 spots in petroleum ether, chloroform, ethyl acetate, and methanol extracts and 3 spots in the Hydro-alcoholic extract with different solvent systems. Conclusion: The results obtained from the study will provide a reliable basis for identification, purity, and quality of the plant.

Garcinia pedunculata Roxb. is an important medicinal plant of North Eastern (NE) region of India, having number of medicinal properties and used against various diseases in folk medicine. An empirical research was designed to carry out evaluation of hepatoprotective activity of the leaves of G. pedunculata with special reference to its putative protective role. Methanolic extract from the dried leaf powder of G. pedunculata Roxb. was prepared by hot continuous extraction method. The prepared extract was investigated at different dose levels for its hepatoprotective nature and further histopathological study was carried out to ascertain the degree of reversing the hepatotoxic manifestation induced by CCl4 (Carbon tetrachloride). LD50 values of the G. pedunculata Roxb. extract was found to be safe up to 2000 mg. The in vivo biological studies on serum and tissues of male Wister rats at the doses of 100 mg, 300 mg and 600 mg/kg body weight respectively was carried out taking Silymarin as standard. The methanolic extract of G. pedunculata Roxb, improved the cholesterol level along with significant improvement of SGPT (Serum Glutamate Pyruvate Transaminase), SGOT (Serum Glutamate Oxaloacetate Transaminase), ALP (Alkaline Phosphatase) and total protein in respect to Silymarin group. The test extract at the dose 600 mg/kg body weight was found to significantly reverse the elevated marker enzymes i.e. SGOT, SGPT, ALP indicating its hepatoprotective role. The higher dose extracts were also found to have pronounced effect on oxidative stress parameters such as GSH and catalase on CCl4 induced rats. The histopathological studies further augmented the protective activity of G. pedunculata leaf extract thereby endorsing the traditional usage of the plant.

Existing understanding of molecular composition of sputum and its role in tuberculosis patients is variously limited to its diagnostic potential. We sought to identify infection induced sputum proteome alteration in active/non tuberculosis patients (A/NTB) and their role in altered lung patho-physiology. Out of the study population (n = 118), sputum proteins isolated from discovery set samples (n = 20) was used for an 8-plex isobaric tag for relative and absolute concentration analysis. A minimum set of protein with at least log2(ATB/NTB) >±1.0 in ATB was selected as biosignature and validated in 32 samples. Predictive accuracy was calculated from area under the receiver operating characteristic curve (AUC of ROC) using a confirmatory set (n = 50) by Western blot analysis. Mass spectrometry analysis identified a set of 192 sputum proteins, out of which a signature of β-integrin, vitamin D binding protein:DBP, uteroglobin, profilin and cathelicidin antimicrobial peptide was sufficient to differentiate ATB from NTB. AUC of ROC of the biosignature was calculated to 0.75. A shift in DBP-antimicrobial peptide (AMP) axis in the lungs of tuberculosis patients is observed. The identified sputum protein signature is a promising panel to differentiate ATB from NTB groups and suggest a deregulated DBP-AMP axis in lungs of tuberculosis patients.

Hypoxia, the low O2 concentration, is a notable element of a large portion of the strong tumors. Having an extensive comprehension of tumor hypoxia condition might be a key to tumor treatment. The gigantic novel works have been done to create multifunctional nanoparticulate approach for hypoxia imaging–guided tumor theranostic. The multifunctional hypoxia imaging–guided tumor treatment could screen the tumor treatment process and assess tumor restorative impact. In the interim, numerous difficulties and constraints are as yet staying inside the use of multifunctional hypoxia nanoparticles. Here we highlight a general view over hypoxia imaging with multifunctional nanoparticles that proved to be exceptionally compelling in tumor theranostic.

Mycobacterium tuberculosis (Mtb) adapts many strategies to persist and replicate inside human tissue. One such strategy is the manipulation of CD4A case-control study was conducted in newly diagnosed active pulmonary tuberculosis (APTBs) patients and 2 sets of controls: (i) individuals infected with latent tuberculosis infection (LTBI) and (ii) healthy close tuberculosis healthy contacts (HCs). The frequencies of different subsets of CD4Frequencies of CD4CD4

Nanomedicine and nanodrug delivery systems have furnished a platform to upgrade drug delivery using the new idea and carrier systems that conventional formulations have failed to acquire. Drug delivery in relation to nanomedicines should be observed as a science and technology of nanocomplex systems that drive to a special mechanism related to diagnosing, treating and inhibiting multiple diseases. As nanocomplex system comprises materials that are designed at the molecular, atomic and macromolecular level, they are generally tiny particles with distinct physicochemical properties. By manipulating their distinct physicochemical properties, nanomedicines and nanodrug delivery systems can control, monitor and repair the biological systems by aligning to address diseases. These advanced technologies can offer significant advantages like higher drug loading capacity, specificity, stability and are capable of delivering both hydrophilic and lipophilic drug molecules. Recently, several nanomedicines have already been marketed by various pharmaceutical and medical device manufacturer companies in the form of polymeric micelles, nanosuspensions, nanocrystals, liposomes, SPIONs and protein-based nanoparticles that confirmed their effectiveness over a longer period. However, the benefits of nanomedicines in the healthcare sector are escorted by challenges in the regulation of such products. Enough knowledge on their efficacy, quality, safety and toxicity must be learned to support their smooth translational research towards clinical applications. The present chapter highlights the recent trends and perspectives of nanomedicines and nanodrug delivery systems with potential benefits to targeted drug delivery.

Nanomedicine is the application of nanobiotechnologies to medicine. This chapter highlights the recent trends and applications of nanobiotechnology in emerging fields of nanodiagnostics, nanotherapeutics, and nanotheranostics including clinical nanomedicine.

In recent days, nanotechnology in the form of nanopharmaceuticals and nanostructured materials has found a significant niche in different spheres of pharmaceutical science, for instance, diagnostic imaging, gene therapy, drug delivery, immunotherapy, microsurgery and dentistry. The polymer-based nanopharmaceuticals have relatively gained the interest of researchers lately, by virtue of their tuneable characteristics to achieve the intended response in targeted drug delivery. This chapter lays special prominence to the inclusion of synthetic and natural biopolymers in nanomedicines. Synthetic biopolymers have been found competent in delivering biologics besides several active pharmaceutical ingredients (API) in multiple clinical complications. This chapter additionally elucidates the employment of natural biopolymers in delivering API derived from both synthetic and natural source. The currently available FDA-approved biopolymer-based nanomedicines and those under clinical trials have been also enumerated.

The surface modification of polymeric nanoparticle (NP) with bioactive ligands and/or secondary polymeric layers is a common strategy to govern the interaction of NPs with cells, proteins, and other biomolecules. But such surface engineering is not always so simple when the surface is chemically nonreactive. Because of this, NP surface modification processes generally employ reactive connector or coupling agents or prefunctionalization of the polymer, which are very tricky and ineffective. However, prefunctionalization of polymers can reduce the ability of drug encapsulation efficiency if the inserted ligands hamper the chemical properties of the polymer. To solve this issue, scientists have discovered a method of dopamine polymerization as a way of NP surfaces functionalization. In brief, this method involves the incubation of raw NPs in a weak alkaline solution of dopamine and subsequent incubation with ligands. This reaction furnishes a universal coating of polydopamine for metals, polymers, and ceramics, irrespective of their physicochemical characteristics. Polydopamine-based surface modified nanomaterials emerge as novel nanocomposite and get the interests in the area of drug delivery and therapy because of their unique physicochemical features, such as multifaceted adhesive property, great chemical reactivity, exceptional biocompatibility and biodegradability, and strong photothermal conversion capacity. This chapter highlights the recent development of polydopamine-based surface modified polymeric nanoparticles for smart drug delivery and therapy.

PURPOSE Detailed understanding of host pathogen interaction in tuberculosis is an important avenue for identifying novel therapeutic targets. Small extracellular vesicles (EVs) like exosomes that are rich in proteins, nucleic acids and lipids, act as messengers and may show altered composition in disease conditions. EXPERIMENTAL DESIGN In this case control study, small EVs are isolated from serum of 58 subjects (all male, 33 (15-70) in years) including drug naive active tuberculosis (ATB: n = 22), non-tuberculosis (NTB: n = 18), and healthy subjects (n = 18). Serum small EVs proteome analysis is carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent sample (n = 36) is used for validation. RESULTS A set of 132 and 68 proteins are identified in iTRAQ-I (ATB/Healthy) and iTRAQ-II (ATB/NTB) experiments, respectively. Four proteins (KYAT3, SERPINA1, HP, and APOC3) show deregulation (log2 -fold change > ±0.48, p

Garcinia pedunculata Roxb. is an important medicinal plant of North Eastern (NE) region of India, having number of medicinal properties and used against various diseases in folk medicine. An empirical research was designed to carry out evaluation of hepatoprotective activity of the leaves of G. pedunculata with special reference to its putative protective role. Methanolic extract from the dried leaf powder of G. pedunculata Roxb. was prepared by hot continuous extraction method. The prepared extract was investigated at different dose levels for its hepatoprotective nature and further histopathological study was carried out to ascertain the degree of reversing the hepatotoxic manifestation induced by CCl(4) (Carbon tetrachloride). LD(50) values of the G. pedunculata Roxb. extract was found to be safe up to 2000 mg. The in vivo biological studies on serum and tissues of male Wister rats at the doses of 100 mg, 300 mg and 600 mg/kg body weight respectively was carried out taking Silymarin as standard. The methanolic extract of G. pedunculata Roxb, improved the cholesterol level along with significant improvement of SGPT (Serum Glutamate Pyruvate Transaminase), SGOT (Serum Glutamate Oxaloacetate Transaminase), ALP (Alkaline Phosphatase) and total protein in respect to Silymarin group. The test extract at the dose 600 mg/kg body weight was found to significantly reverse the elevated marker enzymes i.e. SGOT, SGPT, ALP indicating its hepatoprotective role. The higher dose extracts were also found to have pronounced effect on oxidative stress parameters such as GSH and catalase on CCl(4) induced rats. The histopathological studies further augmented the protective activity of G. pedunculata leaf extract thereby endorsing the traditional usage of the plant.