Secondary metabolites in topical infectious diseases and nanomedicine applications.

Topical infection affects nearly one-third of the world's population; it may result from poor sanitation, hygienic conditions and crowded living and working conditions that accelerate the spread of topical infectious diseases. The problems associated with the anti-infective agents are drug resistance and long-term therapy. Secondary metabolites are obtained from plants, microorganisms and animals, but they are metabolized inside the human body. The integration of nanotechnology into secondary metabolites is gaining attention due to their interaction at the subatomic and skin-tissue levels. Hydrogel, liposomes, lipidic nanoparticles, polymeric nanoparticles and metallic nanoparticles are the most suitable carriers for secondary metabolite delivery. Therefore, the present review article extensively discusses the topical applications of nanomedicines for the effective delivery of secondary metabolites.

Unravelling the potential of mitochondria-targeted liposomes for enhanced cancer treatment.

Mitochondria are the primary organelles of cells involved in various physiochemical and biochemical processes. Owing to their crucial role in cellular metabolism, mitochondria are favored therapeutic targets for the treatment and prevention of cancers. Recently, there has been growing interest in the use of mitochondria-specific functional nanoparticles for targeted delivery of therapeutic agents to these organelles. Among several nanosystems, liposomes have garnered considerable attention owing to their exceptional drug delivery capabilities, biocompatibility, biodegradability, ease of manufacturing and established regulatory guidelines for market approval. In this context, the present review provides a brief insight into the association between mitochondria and tumor formation and advantages of mitochondrial targeting in cancer therapy. Furthermore, it discusses mitochondria-targeting functional liposomes for the treatment of various cancers, such as breast, lung, colon, among others.

Bedaquiline-Loaded Solid Lipid Nanoparticles Drug Delivery in the Management of Non-Small-Cell Lung Cancer (NSCLC).

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (-) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of -0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential.

Biodegradation of di-2-ethylhexyl phthalate by Bacillus firmus MP04 strain: parametric optimization using full factorial design.

Di-2-ethylhexyl phthalate (DEHP) is used as a plasticizer in making plastics and released from landfills. This study attempted to degrade DEHP using microbial isolates. Isolates of Bacillus spp. were tested for their efficacy in degrading DEHP. Degradation was assessed using liquid chromatography-mass spectrometry (LC-MS). The most efficient DEHP degradation was achieved by Bacillus firmus MP04, which has been identified as Bacillus firmus MP04. This strain was found to use DEHP as the sole source of carbon without carbon source supplementation. Full factorial design was used to optimize the conditions for DEHP degradation which revealed the suitability of pH 7, 5% salt concentration, 20 to 37 °C temperature, and yeast extract as a nitrogen source. LC-MS elucidated the possible degradation mechanism via benzoic acid formation. However, prolonged incubation formed a typical compound denatonium benzoate due to reactions with other compounds. As maximum degradation was achieved in 4 days, prolonged incubation is not suggested. It can be concluded that new strain Bacillus firmus MP04 is the most efficient strain among all the tested strains for DEHP degradation.

Baicalin-Loaded Lipid-Polymer Hybrid Nanoparticles Inhibiting the Proliferation of Human Colon Cancer: Pharmacokinetics and In Vivo Evaluation.

This research work is focused on pharmacokinetic and biochemical experiments to assess baicalin-loaded lipid-polymer hybrid nanoparticles (LPHNPs) with colon-targeting specificity. The nanoprecipitation method was used to develop the LPHNPs, and the characterized formulation revealed the 184.3 nm particle size, PDI of 0.177, spherical shape, and zeta potential of -19.8 mV. The baicalin LPHNPs are said to be poorly absorbed in the stomach and small intestine, and in vitro drug release tests have shown that the drug is released mostly in the caecal fluid. Additionally, the LPHNPs showed stability and nonsignificant drug loss at 25 °C for 3 months. The least viable population of baicalin-loaded LPHNPs was detected at a lower IC50 value after 48 h, and no cytotoxicity was observed by blank suspension and blank LPHNPs up to the concentration of 100 µg/mL. Apart from this, the pharmacokinetics study showed that baicalin from LPHNPs is much less absorbed and least available in the blood plasma and maximum available in the colon. Concurrently, organ distribution studies demonstrated that baicalin-loaded LPHNPs were distributed more widely in the colon compared to baicalin suspension. Moreover, baicalin-loaded LPHNPs were found to be superior to a baicalin suspension in reducing elevated liver enzyme levels. In a nutshell, baicalin-loaded LPHNPs show superior efficacy and can be maximally localized into the colon rectal cancer along with systemic availability of the drug.

Resveratrol-Loaded Chia Seed Oil-Based Nanogel as an Anti-Inflammatory in Adjuvant-Induced Arthritis.

Natural anti-inflammatory nutraceuticals may be useful in preventing rheumatoid arthritis from worsening. Resveratrol (RV) and chia seed oil, having antioxidant potential, can assist in avoiding oxidative stress-related disorders. This investigation developed and evaluated resveratrol-loaded chia seed oil-based nanoemulsion (NE) gel formulations through in vitro and in vivo studies. The physical stability and in vitro drug permeability of the chosen formulations (NE1 to NE10) were studied. The optimized RV-loaded nanoemulsion (NE2) had droplets with an average size of 37.48 nm that were homogeneous in shape and had a zeta potential of -18 mV. RV-NE2, with a permeability of 98.21 ± 4.32 µg/cm2/h, was gelled with 1% carbopol-940P. A 28-day anti-arthritic assessment (body weight, paw edema, and levels of pro-inflammatory mediators including TNF-α, IL-6, IL-1ß, and COX-2) following topical administration of RV-NE2 gel showed significant reversal of arthritic symptoms in arthritic Wistar rats induced by Freund's complete adjuvant injection. Therefore, RV-NE2 gel demonstrated the potential to achieve local therapeutic benefits in inflammatory arthritic conditions due to its increased topical bioavailability and balancing of pro-inflammatory mediators.

UPLC-MS/MS Method Development for Simultaneous Estimation of Diclofenac and Resveratrol-Loaded Liposomal Gel Formulation in Mice Skin Model: Application to Dermatokinetic Study.

The current research work describes the development of a simple, fast, sensitive and efficient bioanalytical UPLC/MS-MS method for the simultaneous estimation of diclofenac and resveratrol in mice skin samples. Quetiapine was used as an internal standard (IS). Analytical separation was performed on ACQUITY UPLC C18 Column (2.1 × 100 mm; 1.7 µm) using ammonium acetate (5 mM) in water and methanol (B) with isocratic elution at ratio of (50, 50 v/v) and flow rate of 0.4 mL/min. The duration of separation was maintained for 3 min. Electrospray ionization mass spectrometry in a positive and negative ionization mode was used for detection. Selective ion mode monitoring was used for the quantification of m/z 296.025> 249.93 for diclofenac, m/z 229.09 > 143.03 for resveratrol and MRM/ES+ve mode applied in m/z 384.25> 253.189 for IS transitions from parent to daughter ion. The lower detection and quantification limits were accomplished, and precision (repeatability and intermediate precision) with a coefficient of variation below 10% produced satisfactory results. The developed bioanalytical method was found to be useful for its suitability for the dermatokinetic evaluation of treatments through rat skin. Improvement in AUC (1.58-fold for diclofenac and 1.60-fold for resveratrol) and t1/2 in the dermis (2.13 for diclofenac and 2.21-fold for resveratrol) followed by epidermis was observed for diclofenac and resveratrol-loaded liposomal gel formulation over the conventional gel. Overall, the developed method for the dermatokinetic studies of the above-mentioned dual drugs-loaded liposome gel was found to be reproducible and effective for bioanalytical.

Hispolon-Loaded Liquid Crystalline Nanoparticles: Development, Stability, In Vitro Delivery Profile, and Assessment of Hepatoprotective Activity in Hepatocellular Carcinoma.

The present work describes the development and characterization of liquid crystalline nanoparticles of hispolon (HP-LCNPs) for treating hepatocellular carcinoma. HP-LCNPs were prepared by a top-down method utilizing GMO as the lipid and Pluronic F-127 as the polymeric stabilizer. The prepared formulations (HP1-HP8) were tested for long-term stability, where HP5 showed good stability with a particle size of 172.5 ± 0.3 nm, a polydispersity index (PDI) of 0.38 ± 0.31 nm, a zeta potential of -10.12 mV ± 0.05, an entrapment efficiency of 86.81 ± 2.5%, and a drug loading capacity of 12.51 ± 1.12%. Optical photomicrography and transmission electron microscopy images demonstrated a consistent, low degree of aggregation and a spherical shape of LCNPs. The effect of temperature and pH on the optimized formulation (HP5) indicated good stability at 45 °C and at pH between 2 and 5. In vitro gastrointestinal stability indicated no significant change in the particle size, PDI, and entrapment efficiency of the drug. The drug release study exhibited a biphasic pattern in simulated gastric fluid (pH 1.2) for 2 h and simulated intestinal fluid (pH 7.4) for up to 24 h, while the best fitting of the profile was observed with the Higuchi model, indicating the Fickian diffusion mechanism. The in vivo pharmacokinetic study demonstrated nearly 4.8-fold higher bioavailability from HP5 (AUC: 1774.3 ± 0.41 µg* h/mL) than from the HP suspension (AUC: 369.11 ± 0.11 µg* h/mL). The anticancer activity evaluation revealed a significant improvement in antioxidant parameters and serum hepatic biomarkers (SGOT, SGPT, ALP, total bilirubin, and GGT) in the diethyl nitrosamine-treated group of rats with the optimized LCNP formulation (HP5) vis-à-vis HP suspension.

EGF-functionalized lipid-polymer hybrid nanoparticles of 5-fluorouracil and sulforaphane with enhanced bioavailability and anticancer activity against colon carcinoma.

The present research work describes development of dual drug-loaded lipid-polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)-functionalized LPHNPs coloaded with 5-fluorouracil (FU) and sulforaphane (SFN) were prepared by one-step nanoprecipitation method. Box-Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential -25.3 mV, and drug loading efficiency 19-20.3% for 5-FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non-Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT-15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF-functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF-functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma.

Crotamiton-loaded tea tree oil containing phospholipid-based microemulsion hydrogel for scabies treatment: in vitro, in vivo evaluation, and dermatokinetic studies.

Crotamiton (CRT) is a commonly approved drug prescribed for the scabies treatment in many countries across the globe. However, poor aqueous solubility and low bioavailability, and side effects restrict its use. To avoid such issues, an appropriate carrier system is necessary which can address the aforementioned challenges for attaining enhanced biopharmaceutical attributes. The current study intends to provide a detailed account on the development and evaluation of CRT-loaded microemulsion (ME) hydrogel formulation containing tea tree oil (TTO) for improved drug delivery for scabies treatment in a safe and effective manner. Pseudo-ternary phase diagrams were constructed with TTO as the oily phase, and Cremophor®EL was used as the surfactant in a mass ratio 2:1 with co-surfactants (mixture of phospholipid 90G and Transcutol®P), and aqueous solution as the external phase. The optimized drug-loaded ME formulation was evaluated for skin penetration, retention, compliance, and dermatokinetics. The nonirritant behavior of the formulation was revealed by skin histopathology, which showed no changes in normal skin histology. In comparison to the conventional product, dermatokinetic experiments revealed that CRT has greater penetration and distribution in the epidermis of the mice skin. The findings imply that the proposed lipid-based ME hydrogel can aid in the resolution of CRT issues by providing a better and safer delivery option to epidermis and deeper epidermis in substantial quantities.

Three 'D's: Design approach, dimensional printing, and drug delivery systems as promising tools in healthcare applications.

The development of pharmaceutical drug products is required for the treatment of disease, which has resulted in an increasing number of approvals by regulatory agencies across the globe. To establish a hassle-free manufacturing process, the systematic use of a quality-by-design (QbD) approach combined with process analytical technology (PAT) and printing techniques can revolutionize healthcare applications. Printing technology has been emerged in various dimensions, such as 3D, 4D, and 5D printing, with respect to their production capabilities, durability, and accuracy of pharmaceutical manufacturing, which can efficiently deliver novel patient-centric healthcare products with holistic characteristics. In this review, we provide current trends in pharmaceutical product development using a design approach and high-quality printing techniques.

Paclitaxel and naringenin-loaded solid lipid nanoparticles surface modified with cyclic peptides with improved tumor targeting ability in glioblastoma multiforme.

The present work describes the systematic development of paclitaxel and naringenin-loaded solid lipid nanoparticles (SLNs) for the treatment of glioblastoma multiforme (GBM). So far only temozolomide therapy is available for the GBM treatment, which fails by large amount due to poor brain permeability of the drug and recurrent metastasis of the tumor. Thus, we investigated the drug combination containing paclitaxel and naringenin for the treatment of GBM, as these drugs have individually demonstrated significant potential for the management of a wide variety of carcinoma. A systematic product development approach was adopted where risk assessment was performed for evaluating the impact of various formulation and process parameters on the quality attributes of the SLNs. I-optimal response surface design was employed for optimization of the dual drug-loaded SLNs prepared by micro-emulsification method, where Percirol ATO5 and Dynasan 114 were used as the solid lipid and surfactant, while Lutrol F188 was used as the stabilizer. Drug loaded-SLNs were subjected to detailed in vitro and in vivo characterization studies. Cyclic RGD peptide sequence (Arg-Gly-Asp) was added to the formulation to obtain the surface modified SLNs which were also evaluated for the particle size and surface charge. The optimized drug-loaded SLNs exhibited particle size and surface charge of 129 nm and 23 mV, drug entrapment efficiency >80% and drug loading efficiency >7%. In vitro drug release study carried out by micro dialysis bag method indicated more than 70% drug was release observed within 8 h time period. In vivo pharmacokinetic evaluation showed significant improvement (p < 0.05) in drug absorption parameters (Cmax and AUC) from the optimized SLNs over the free drug suspension. Cytotoxicity evaluation on U87MG glioma cells indicated SLNs with higher cytotoxicity as compared to that of the free drug suspension (p < 0.05). Evaluation of uptake by florescence measurement indicated superior uptake of SLNs tagged with dye over the plain dye solution. Overall, the dual drug-loaded SLNs showed better chemoprotective effect over the plain drug solution, thus construed superior anticancer activity of the developed nanoformulation in the management of glioblastoma multiforme.

Probing sulfatide-tissue lectin recognition with functionalized glycodendrimersomes.

The small 3-O-sulfated galactose head group of sulfatides, an abundant glycosphingolipid class, poses the (sphinx-like) riddle on involvement of glycan bridging by tissue lectins (sugar code). First, synthesis of head group derivatives for functionalization of amphiphilic dendrimers is performed. Aggregation of resulting (biomimetic) vesicles, alone or in combination with lactose, demonstrates bridging by a tissue lectin (galectin-4). Physiologically, this can stabilize glycolipid-rich microdomains (rafts) and associate sulfatide-rich regions with specific glycoproteins. Further testing documents importance of heterobivalency and linker length. Structurally, sulfatide recognition by galectin-8 is shown to involve sphingosine's OH group as substitute for the 3'-hydroxyl of glucose of lactose. These discoveries underscore functionality of this small determinant on biomembranes intracellularly and on the cell surface. Moreover, they provide a role model to examine counterreceptor capacity of more complex glycans of glycosphingolipids and to start their bottom-up glycotope surface programming.

Nanotechnology Based Approach for Hepatocellular Carcinoma Targeting.

Hepatocellular carcinoma (HCC) is the primary liver cancer that has shown a high incidence and mortality rate worldwide among several types of cancers. A large variety of chemotherapeutic agents employed for the treatment have a limited success rate owing to their limited site-specific drug targeting ability. Thus, there is a demand to develop novel approaches for the treatment of HCC. With advancements in nanotechnology-based drug delivery approaches, the challenges of conventional chemotherapy have been continuously decreasing. Nanomedicines constituted of lipidic and polymeric composites provide a better platform for delivering and opening new pathways for HCC treatment. A score of nanocarriers such as surface-engineered liposomes, nanoparticles, nanotubes, micelles, quantum dots, etc., has been investigated in the treatment of HCC. These nanocarriers are considered to be highly effective clinically for delivering chemotherapeutic drugs with high site-specificity ability and therapeutic efficiency. The present review highlights the current focus on the application of nanocarrier systems using various ligand-based receptor-specific targeting strategies for the treatment and management of HCC. Moreover, the article has also included information on the current clinically approved drug therapy for hepatocellular carcinoma treatment and updates of regulatory requirements for approval of such nanomedicines.

Nanocarriers-loaded with natural actives as newer therapeutic interventions for treatment of hepatocellular carcinoma.

Introduction: Cancer has always been a menace for the society. Hepatocellular carcinoma (HCC) is one of the most lethal and 3rdlargest causes of deaths around the world.Area covered: The emergence of natural actives is considered as the greatest boon for fighting cancer. The natural actives take precedence over the traditional chemotherapeutic drugs in terms of their multi-target, multi-level and coordinated effects in the treatment of HCC. Literature reports have indicated the tremendous potential of bioactive natural products in inhibiting the HCC via molecular drug targeting, augmented bioavailability, and the ability for both passive or active targeting and stimulus-responsive drug release characteristics. This review provides a newer treatment approaches involved in the mechanism of action of different natural actives used for the HCC treatment via different molecular pathways. Besides, the promising advantage of natural bioactive-loaded nanocarriers in HCC treatment has also been also presented in this review. Expert opinion: The remarkable outcomes have been observed with therapeutic efficacy of the nanocarriers of natural actives in the treatment of HCC.Furthermore, it requires a thorough assessment of the safety and efficacy evaluation of the nanocarriers for the delivery of targeted natural active ingredients in HCC.].

Synthesis, In-Vitro and In-Silico Evaluation of Silver Nanoparticles with Root Extract of Withania somnifera for Antibacterial Activity via Binding of Penicillin-Binding Protein-4.

BACKGROUND: Metal Nanoparticles (NPs) have been widely used for various applications in biomedical sciences, including in drug delivery, and as therapeutic agents, but limited owing to their toxicity towards the healthy tissue. This warrants an alternative method, which can achieve the desired activity with much reduced or no toxicity. Being a biological product, Withania somnifera (W. somnifera) is environment friendly, besides being less toxic as compared to metal-based NPs. However, the exact mechanism of action of W. somnifera for its antibacterial activities has not been studied so far. OBJECTIVE: To develop "silver nanoparticles with root extract of W. somnifera (AgNPs-REWS)" for antimicrobial and anticancer activities. Furthermore, the analysis of their mechanism of action will be studied. METHODS: Using the in-silico approach, the molecular docking study was performed to evaluate the possible antibacterial mechanism of W. somnifera phytochemicals such as Anaferine, Somniferine, Stigmasterol, Withaferin A, Withanolide- A, G, M, and Withanone by the inhibition of Penicillin- Binding Protein 4 (PBP4). Next, we utilized a bottom-up approach for the green synthesis of AgNPs- REWS, performed an in-detail phytochemical analysis, confirmed the AgNPs-REWS by SEM, UVvisible spectroscopy, XRD, FT-IR, and HPLC. Eventually, we examined their antibacterial activity. RESULTS: The result of molecular docking suggests that WS phytochemicals (Somniferine, Withaferin A, Withanolide A, Withanolide G, Withanolide M, and Withanone) possess the higher binding affinity toward the active site of PBP4 as compared to the Ampicillin (-6.39 kcal/mol) reference molecule. These phytochemicals predicted as potent inhibitors of PBP4. Next, as a proof-of-concept, AgNPs- REWS showed significant antibacterial effect as compared to crude, and control; against Xanthomonas and Ralstonia species. CONCLUSION: The in-silico and molecular docking analysis showed that active constituents of W. somnifera such as Somniferine, Withaferin A, Withanolide A, Withanolide G, Withanolide M, and Withanone possess inhibition potential for PBP4 and are responsible for the anti-bacterial property of W. somnifera extract. This study also establishes that AgNPs via the green synthesis with REWS showed enhanced antibacterial activity towards pathogenic bacteria.

Glycan binding profile of a fucolectin-related protein (FRP) encoded by the SP2159 gene of Streptococcus pneumoniae.

The recombinant fucolectin-related protein (FRP) of unknown function, encoded by the SP2159 gene of Streptococcus pneumoniae, was expressed in E. coli. In this study, its glycan-recognition epitopes and their binding potencies were examined by enzyme-linked lectinosorbent and inhibition assays. The results indicate that FRP reacted strongly with human blood group ABH and l-Fucα1→2-active glycotopes and in their polyvalent (super) forms. When expressed by mass relative potency, the binding affinities of FRP to poly-l-Fucα1→glycotopes were about 5.0 × 105 folds higher than that of the mono-l-Fucα1→glycotope form. This unique binding property of FRP can be used as a special tool to differentiate complex forms of l-Fucα1→2 and other forms of glycotopes.

Awareness of Biomedical Waste Management in Dental Students in Different Dental Colleges in Nepal.

AIM: The aim of this study is to assess the awareness of biomedical waste management in dental students of various dental colleges of Nepal. METHODOLOGY: A structured pretested questionnaire was used among 434 (323 males and 111 females) undergraduate dental students of five different dental colleges of Nepal. First part of the questionnaire was used to describe demographic profile of the participants. Second part of the questionnaire assessed the knowledge, attitude, and practice regarding biomedical waste management. Chi-square test was applied to find out the association between different responses obtained from different colleges. RESULT: Majority (91.82%) of participants had a positive attitude towards safe management of biomedical waste. Regarding the knowledge of BMW management policies, majority of the students (83.1% to 98.9%) had positive attitude towards the safe management of biomedical waste, whereas more than 50% of the students were unaware of the guidelines laid down by Government of Nepal. Regarding biomedical waste disposal technique in the hospital, only 29.9% to 79.8% are aware; this shows that there is lack of strict protocol in the BMW management. Association between different responses and colleges for "improper waste management causes various health hazards" ranged from 93.3% to 98.9%. CONCLUSION: There exists a lacuna in the knowledge and practice of biomedical waste management among the undergraduate dental students in Nepal. Since the students had positive attitude towards addressing this concern, workshops and trainings related to proper biomedical waste management would be a step forward towards attaining a healthy environment for the future.

Network monitoring of adhesion/growth-regulatory galectins: localization of the five canonical chicken proteins in embryonic and maturing bone and cartilage and their introduction as histochemical tools.

Divergence from an ancestral gene leads to a family of homologous proteins. Whether they are physiologically distinct, similar, or even redundant is an open question in each case. Defining profiles of tissue localization is a step toward giving diversity a functional meaning. Due to the significance of endogenous sugar receptors (lectins) as effectors for a wide range of cellular activities we have focused on galectins. The comparatively low level of network complexity constituted by only five canonical proteins makes chicken galectins (CGs) an attractive choice to perform comprehensive analysis, here studied on bone/cartilage as organ system. Galectin expression was monitored by Western blotting and immunohistochemistry using non-cross-reactive antibodies. Overall, three galectins (CG-1B, CG-3, CG-8) were present with individual expression patterns, one was found exclusively in the mesenchyme (CG-1A), the fifth (CG-2) not being detectable. The documented extents of separation are a sign for functional divergence; in cases with overlapping stainings, as for example in the osteoprogenitor layer or periosteum, cooperation may also be possible. Recombinant production enabled the introduction of the endogenous lectins as tools for binding-site localization. Their testing revealed developmental regulation and cell-type-specific staining. Of relevance for research on mammalian galectins, this study illustrates that certain cell types can express more than one galectin, letting functional interrelationships appear likely. Thus, complete network analysis irrespective of its degree of complexity is mandatory.

Biochemical and histopathological effects on liver due to acute oral toxicity of aqueous leaf extract of Ecliptaalba on female Swiss albino mice.

BACKGROUND: Limited data is available about the toxicity of herbal remedies used for self-medication. Since a popular medicinal plant Ecliptaalba contains various bioactive molecules, the present study aimed to observe the biochemical and histological changes in liver associated with acute oral toxicity (LD50) of aqueous extract of E. alba (L.) Hassk. in female Swiss albino mice. MATERIALS AND METHODS: For the acute oral toxicity study, the animals were divided into six groups of 6 mice each. Group- I was normal control and the treatment groups were administered aqueous leaf extract of E. alba orally at different doses of 500 mg (group - I),1750 mg (group-III), 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg/ kg/b.wt.(group- VI) for seven consecutive days. The mice were sacrificed on the eighth day and blood was collected for the analysis of ALP (alkaline phosphatase), SGPT (serum glutamic pyruvic transferase), total protein and albumin. The liver was dissected, weighed, and processed for histopathological analysis. RESULTS: The LD50 was found to be 2316.626 mg/kg /body weight in female mice. Serum SGPT, total protein and albumin increased in treated group- IV (P < 0.05), V (P < 0.01), and VI (P < 0.01) as compared to the control (group- I). ALP level significantly decreased in the treated group- IV (P < 0.05), V (P < 0.01) and VI (P < 0.01). Histopathological changes were observed at dose of 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg (group- VI). CONCLUSION: It was concluded that oral administration of aqueous leaf extract of E. alba had detrimental effects on biochemical parameters and induced histopathological alterations in liver of female Swiss albino mice at doses higher than 2000 mg/kg/day indicating that its indiscriminate use should be avoided.