Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for gastroprotection in patients undergoing percutaneous coronary intervention (PCI), who are at increased risk of gastrointestinal bleeding due to antiplatelet therapy. However, emerging evidence suggests that PPIs may adversely impact cardiovascular outcomes. This systematic review and meta-analysis sought to assess the relationship between using PPIs and cardiovascular outcomes in patients following PCI. METHODS: We searched various databases up to March 15, 2024, for observational studies and randomized controlled trials (RCTs) assessing the cardiovascular effects of PPIs in PCI patients. Data were extracted on study characteristics, patient demographics, PPI use, and cardiovascular outcomes. The Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool 2 assessed study quality. Meta-analyses were conducted using a random-effects model using R software version 4.3. RESULTS: A total of 21 studies involving diverse populations and study designs were included. Observational studies suggested a moderate increase in risk for composite cardiovascular diseases (CVD), myocardial infarction (MI), and major adverse cardiac events (MACE) associated with PPI use, with pooled hazard ratios (HRs) of 1.20 (95% CI: 1.093-1.308) for CVD, 1.186 (95% CI: 1.069-1.303) for MI, and 1.155 (95% CI: 1.001-1.309) for MACE. However, RCTs showed no significant link between PPI therapy and negative cardiovascular events (Relative Risk: 1.016, 95% CI: 0.878-1.175). Substantial heterogeneity was observed among observational studies but not RCTs. CONCLUSION: The findings indicate that while observational studies suggest a potential risk of adverse cardiovascular events with post-PCI use of PPI, RCTs do not support this association. Further large-scale, high-quality studies are required to understand the cardiovascular implications of individual PPIs better and optimize patient management post-PCI. This analysis shows the complexity of PPI use in patients with coronary artery diseases and the necessity to balance gastroprotective benefits against potential cardiovascular risks.

Recellularization of Acellular Xeno Kidney Scaffold: An In Vivo Method to Generate Bioartificial Kidney.

A significant hurdle for kidney tissue engineering is reproducing the complex three-dimensional structure of the kidney. In our study, a stepwise approach of generating a reproducible Xeno kidney scaffold from a goat kidney is described, which can be implanted and recellularized by host cells. We have proposed a combination of sodium dodecyl sulfate and Triton-X-100-based protocol to generate a reproducible Xeno kidney scaffold, which was then analyzed by histology, DNA quantification, SEM, and renal angiography. Further, a small portion from the cortico-medullar region of the acellular scaffold was implanted in the rat's kidney subcapsular pocket for a period of 1 month, to check the recruitment of host cells into the scaffold. Post implantation, the extracellular matrix of the scaffold was well preserved and it did not induce any damage or inflammation in the native kidney. Implantation of the Xeno scaffold resulted in apparent early vascularization which helped in the recruitment of the host cells, which was characterized by histology, immunohistochemistry, and scanning electron microscopy. Implanted Xeno scaffold showed AQP-1, Nephrin, α-SMA, and VEGF expression in proximal tubules and renal glomerulus. Importantly, Ki-67 and WTAP-expressing cells were also observed near proximal tubules suggesting a high level of proliferation in the scaffold. Thus, showing the potential of Xeno kidney development that can be recellularized by the host cell to engineer into a functional kidney.

Buparvaquone Induces Ultrastructural and Physiological Alterations Leading to Mitochondrial Dysfunction and Caspase-Independent Apoptotic Cell Death in Leishmania donovani.

Leishmaniasis is a neglected tropical disease (endemic in 99 countries) caused by parasitic protozoa of the genus Leishmania. As treatment options are limited, there is an unmet need for new drugs. The hydroxynaphthoquinone class of compounds demonstrates broad-spectrum activity against protozoan parasites. Buparvaquone (BPQ), a member of this class, is the only drug licensed for the treatment of theileriosis. BPQ has shown promising antileishmanial activity but its mode of action is largely unknown. The aim of this study was to evaluate the ultrastructural and physiological effects of BPQ for elucidating the mechanisms underlying the in vitro antiproliferative activity in Leishmania donovani. Transmission and scanning electron microscopy analyses of BPQ-treated parasites revealed ultrastructural effects characteristic of apoptosis-like cell death, which include alterations in the nucleus, mitochondrion, kinetoplast, flagella, and the flagellar pocket. Using flow cytometry, laser scanning confocal microscopy, and fluorometry, we found that BPQ induced caspase-independent apoptosis-like cell death by losing plasma membrane phospholipid asymmetry and cell cycle arrest at sub-G0/G1 phase. Depolarization of the mitochondrial membrane leads to the generation of oxidative stress and impaired ATP synthesis followed by disruption of intracellular calcium homeostasis. Collectively, these findings provide valuable mechanistic insights and demonstrate BPQ's potential for development as an antileishmanial agent.

Impact of age at first calving on fertility and production performance in Murrah buffalo.

The present study analyses the effect of age at first calving (AFC) on future fertility and productivity in Murrah buffaloes. The data of 314 buffalo heifers of animal farm section, ICAR-CIRB, Hisar were collected over a period of 9 years from 2010 to 2018. The buffalo heifers were categorized into six groups according to the AFC named as 30-35, 36-41, 42-47, 48-53, 54-59 and 60-65 months. The influence of AFC on standard lactation milk (SLMY), peak yield (PY), days in milk (DIM), calving to first service, service per conception, calving to conception interval (CCI) and calving interval till fifth lactation were studied. The study revealed poor productive traits in buffalo heifers calved at younger age (30-35 months) during first parity. The productive value positively corresponded with increase in AFC. During successive lactations, higher mean milk yield (SLMY and PY) was found in groups with 36-41, 42-47 and 48-53 months. The mean number of services per conception was lower in buffalo heifers with 36-41 and 42-47 months following first calving till fifth lactation. Similarly, the said groups had lower mean calving to first service, CCI and CI up to fifth lactation. The survival rate was higher in heifers with AFC 36-41, 42-47, 48-53 and 54-59 months than with AFC 30-35 and 60-65 months. The buffalo heifers with 36-41 and 42-47 months of AFC had higher survival rate and better productive and reproductive traits till fifth parity in the current study. The study concluded that a minimum ideal AFC of 36-41 months yielded the highest productive gain.

Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA.

Regulation of RNA stability and translation by RNA-binding proteins (RBPs) is a crucial process altering gene expression. Musashi family of RBPs comprising Msi1 and Msi2 is known to control RNA stability and translation. However, despite the presence of MSI2 in the heart, its function remains largely unknown. Here, we aim to explore the cardiac functions of MSI2. We confirmed the presence of MSI2 in the adult mouse, rat heart, and neonatal rat cardiomyocytes. Furthermore, Msi2 was significantly enriched in the heart cardiomyocyte fraction. Next, using RNA-seq data and isoform-specific PCR primers, we identified Msi2 isoforms 1, 4, and 5, and two novel putative isoforms labeled as Msi2 6 and 7 to be expressed in the heart. Overexpression of Msi2 isoforms led to cardiac hypertrophy in cultured cardiomyocytes. Additionally, Msi2 exhibited a significant increase in a pressure-overload model of cardiac hypertrophy. We selected isoforms 4 and 7 to validate the hypertrophic effects due to their unique alternative splicing patterns. AAV9-mediated overexpression of Msi2 isoforms 4 and 7 in murine hearts led to cardiac hypertrophy, dilation, heart failure, and eventually early death, confirming a pathological function for Msi2. Using global proteomics, gene ontology, transmission electron microscopy, seahorse, and transmembrane potential measurement assays, increased MSI2 was found to cause mitochondrial dysfunction in the heart. Mechanistically, we identified Cluh and Smyd1 as direct downstream targets of Msi2. Overexpression of Cluh and Smyd1 inhibited Msi2-induced cardiac malfunction and mitochondrial dysfunction. Collectively, we show that Msi2 induces hypertrophy, mitochondrial dysfunction, and heart failure.

Cryostress induces fragmentation and alters the abundance of sperm transcripts associated with fertilizing competence and reproductive processes in buffalo.

The study aimed to assess the influence of cryostress on RNA integrity and functional significance in sperm fertilizing ability. The fresh and post-thawed buffalo sperm (n = 6 each) samples were evaluated for their functional attributes, and sperm total RNA was subjected to transcriptome sequencing followed by validation using real-time PCR and dot blot. Overall, 6911 genes had an expression of FPKM > 1, and among these 431 genes were abundantly expressed (FPKM > 20) in buffalo sperm. These abundantly expressed genes regulate reproductive functions such as sperm motility (TEKT2, SPEM1, and PRM3, FDR = 1.10E-08), fertilization (EQTN, PLCZ1, and SPESP1, FDR = 7.25E-06) and the developmental process involved in reproduction (SPACA1, TNP1, and YBX2, FDR = 7.21E-06). Cryopreservation significantly (p < 0.05) affected the structural and functional membrane integrities of sperm. The expression levels of transcripts that regulate the metabolic activities and fertility-related functions were compromised during cryopreservation. Interestingly, cryostress induces the expression of genes involved (p < 0.05) in chemokine signaling (CX3CL1, CCL20, and CXCR4), G-protein coupled receptor binding (ADRB1, EDN1, and BRS3), translation (RPS28, MRPL28, and RPL18A), oxidative phosphorylation (ND1, ND2, and COX2), response to reactive oxygen species (GLRX2, HYAL2, and EDN1), and immune responses (CX3CL1, CCL26, and TBXA2R). These precociously expressed genes during cryopreservation alter the signaling mechanisms that govern sperm functional competence and can impact fertilization and early embryonic development.

Lignocellulolytic extremozymes and their biotechnological applications.

Lignocellulolytic enzymes are used in different industrial and environmental processes. The rigorous operating circumstances of these industries, however, might prevent these enzymes from performing as intended. On the other side, extremozymes are enzymes produced by extremophiles that can function in extremely acidic or basic; hot or cold; under high or low salinity conditions. These severe conditions might denature the normal enzymes that are produced by mesophilic microorganisms. The increased stability of these enzymes has been contributed to a number of conformational modifications in their structures. These modifications may result from a few amino acid substitutions, an improved hydrophobic core, the existence of extra ion pairs and salt bridges, an increase in compactness, or an increase in positively charged amino acids. These enzymes are the best option for industrial and bioremediation activities that must be carried out under difficult conditions due to their improved stability. The review, therefore, discusses lignocellulolytic extremozymes, their structure and mechanisms along with industrial and biotechnological applications.

Ethyl Isothiocyanate as a Novel Antifungal Agent Against Candida albicans.

In the recent years, occurrence of candidiasis has increased drastically which leads to significant mortality and morbidity mainly in immune compromised patients. Glucosinolate (GLS) derivatives are reported to have antifungal activities. Ethyl isothiocyanate (EITC) and its antifungal activity and mechanism of action is still unclear against Candida albicans. The present work was designed to get a mechanistic insight in to the anti-Candida efficacy of EITC through in vitro and in vivo studies. EITC inhibited C. albicans planktonic growth at 0.5 mg/ml and virulence factors like yeast to hyphal form morphogenesis (0.0312 mg/ml), adhesion to polystyrene surface (0.0312 mg/ml) and biofilm formation (developing biofilm at 2 mg/ml and mature biofilm at 0.5 mg/ml) effectively. EITC blocked ergosterol biosynthesis and arrested C. albicans cells at S-phase. EITC caused ROS-dependent cellular death and nuclear or DNA fragmentation. EITC at 0.0312 mg/ml concentration regulated the expression of genes involved in the signal transduction pathway and inhibited yeast to hyphal form morphogenesis by upregulating TUP1, MIG1, and NRG1 by 3.10, 5.84 and 2.64-fold, respectively and downregulating PDE2 and CEK1 genes by 15.38 and 2.10-fold, respectively. EITC has showed haemolytic activity at 0.5 mg/ml concentration. In vivo study in silk worm model showed that EITC has toxicity to C. albicans at 0.5 mg/ml concentration. Thus, from present study we conclude that EITC has antifungal activity and to reduce its MIC and toxicity, combination study with other antifungal drugs need to be done. EITC and its combinations might be used as alternative therapeutics for the prevention and treatment of C. albicans infections.

EEG-Based Emotion Classification in Financial Trading Using Deep Learning: Effects of Risk Control Measures.

Day traders in the financial markets are under constant pressure to make rapid decisions and limit capital losses in response to fluctuating market prices. As such, their emotional state can greatly influence their decision-making, leading to suboptimal outcomes in volatile market conditions. Despite the use of risk control measures such as stop loss and limit orders, it is unclear if these strategies have a substantial impact on the emotional state of traders. In this paper, we aim to determine if the use of limit orders and stop loss has a significant impact on the emotional state of traders compared to when these risk control measures are not applied. The paper provides a technical framework for valence-arousal classification in financial trading using EEG data and deep learning algorithms. We conducted two experiments: the first experiment employed predetermined stop loss and limit orders to lock in profit and risk objectives, while the second experiment did not employ limit orders or stop losses. We also proposed a novel hybrid neural architecture that integrates a Conditional Random Field with a CNN-BiLSTM model and employs Bayesian Optimization to systematically determine the optimal hyperparameters. The best model in the framework obtained classification accuracies of 85.65% and 85.05% in the two experiments, outperforming previous studies. Results indicate that the emotions associated with Low Valence and High Arousal, such as fear and worry, were more prevalent in the second experiment. The emotions associated with High Valence and High Arousal, such as hope, were more prevalent in the first experiment employing limit orders and stop loss. In contrast, High Valence and Low Arousal (calmness) emotions were most prominent in the control group which did not engage in trading activities. Our results demonstrate the efficacy of our proposed framework for emotion classification in financial trading and aid in the risk-related decision-making abilities of day traders. Further, we present the limitations of the current work and directions for future research.

Silver nanomaterials: synthesis and (electro/photo) catalytic applications.

In view of their unique characteristics and properties, silver nanomaterials (Ag NMs) have been used not only in the field of nanomedicine but also for diverse advanced catalytic technologies. In this comprehensive review, light is shed on general synthetic approaches encompassing chemical reduction, sonochemical, microwave, and thermal treatment among the preparative methods for the syntheses of Ag-based NMs and their catalytic applications. Additionally, some of the latest innovative approaches such as continuous flow integrated with MW and other benign approaches have been emphasized that ultimately pave the way for sustainability. Moreover, the potential applications of emerging Ag NMs, including sub nanomaterials and single atoms, in the field of liquid-phase catalysis, photocatalysis, and electrocatalysis as well as a positive role of Ag NMs in catalytic reactions are meticulously summarized. The scientific interest in the synthesis and applications of Ag NMs lies in the integrated benefits of their catalytic activity, selectivity, stability, and recovery. Therefore, the rise and journey of Ag NM-based catalysts will inspire a new generation of chemists to tailor and design robust catalysts that can effectively tackle major environmental challenges and help to replace noble metals in advanced catalytic applications. This overview concludes by providing future perspectives on the research into Ag NMs in the arena of electrocatalysis and photocatalysis.

Wheat straw-based microbial electrochemical reactor for azo dye decolorization and simultaneous bioenergy generation.

Microbial fuel cells have emerged as a technique that can effectively treat wastewater with simultaneous electricity generation. The present study explored the performance of microbial fuel cell for decolorizing and degradation of azo dyes including, remazol brilliant blue (RBB), mordant blue 9 (MB9), acid red1 (AR1), and orange G (OG), while, simultaneously generating electricity. Wheat straw and its hydrolysate was used as a potential substrate in MFC. The hydrolysate was prepared through the degradation of wheat straw by P. floridensis, P. brevispora and P. chrysosporium, while the yeast Pichia fermentans was used as biocatalyst. Dye decolorization was carried out in a fungus-yeast mediated single-chambered MFC batch mode, U-shaped reactor, and bottle reactor in continuous mode. The maximum power density recorded in U shaped continuous reactor was 34.99 mW m-2 on 21st day of the experiment. The best response of dye decolorization was observed in the case of MB9 (96%) with P. floridensis in the continuous electrochemical reactor followed by RBB (90-95%), OG (76%), and AR1 (38%). The toxicity of the treated wastewater was assessed using phytotoxicity analysis.

Ingeniously designed Silica nanostructures as an exceptional support: Opportunities, potential challenges and future prospects for viable degradation of pesticides.

Despite significant advancements in modern agricultural practices, efficient handling of pesticides is a must as they are continuously defiling our terrestrial as well as aquatic life. During the last couple of decades, substantial efforts by various research groups have been devoted to find innovative solutions to remove pesticides from our environment in a greener way. In this regard, functionalized silica nanoparticles (NPs) have gained considerable attention of scientific community due to their notable properties such as amenable design, large surface area as well as fine-tunable and uniform pore structures which make them an ideal material for pesticides removal. The present review aims to proffer current scientific progress attained by silica-based nanostructures as an excellent material for effective removal of noxious agrochemicals. Further, a brief discussion on the synthetic strategies as well as intrinsic benefits associated with different morphologies of silica have also been highlighted in this article. It also summarizes the recent reports on silica assisted degradation of pesticides via enzymatic, chemical as well as advanced oxidation protocols. Additionally, it presents a critical analysis of different support materials for decontamination of our ecosystem. The review concludes with potential challenges, their possible solutions along with key knowledge gaps and future research directions for successful deployment of silica supported materials in degradation of pesticides at commercial scale.

Modeling Bitcoin Prices using Signal Processing Methods, Bayesian Optimization, and Deep Neural Networks.

Bitcoin is a volatile financial asset that runs on a decentralized peer-to-peer Blockchain network. Investors need accurate price forecasts to minimize losses and maximize profits. Extreme volatility, speculative nature, and dependence on intrinsic and external factors make Bitcoin price forecast challenging. This research proposes a reliable forecasting framework by reducing the inherent noise in Bitcoin time series and by examining the predictive power of three distinct types of predictors, namely fundamental indicators, technical indicators, and univariate lagged prices. We begin with a three-step hybrid feature selection procedure to identify the variables with the highest predictive ability, then use Hampel and Savitzky-Golay filters to impute outliers and remove signal noise from the Bitcoin time series. Next, we use several deep neural networks tuned by Bayesian Optimization to forecast short-term prices for the next day, three days, five days, and seven days ahead intervals. We found that the Deep Artificial Neural Network model created using technical indicators as input data outperformed other benchmark models like Long Short Term Memory, Bi-directional LSTM (BiLSTM), and Convolutional Neural Network (CNN)-BiLSTM. The presented results record a high accuracy and outperform all existing models available in the past literature with an absolute percentage error as low as 0.28% for the next day forecast and 2.25% for the seventh day for the latest out of sample period ranging from Jan 1, 2021, to Nov 1, 2021. With contributions in feature selection, data-preprocessing, and hybridizing deep learning models, this work contributes to researchers and traders in fundamental and technical domains.

Copper@ZIF-8 Core-Shell Nanowires for Reusable Antimicrobial Face Masks.

SARS-CoV-2 and other respiratory viruses spread via aerosols generated by infected people. Face masks can limit transmission. However, widespread use of disposable masks consumes tremendous resources and generates waste. Here, a novel material for treating blown polypropylene filtration media used in medical-grade masks to impart antimicrobial activity is reported. To produce thin copper@ZIF-8 core-shell nanowires (Cu@ZIF-8 NWs), Cu NWs are stabilized using a pluronic F-127 block copolymer, followed by growth of ZIF-8 to obtain uniform core-shell structures. The Cu@ZIF-8 NWs are applied to filtration media by dip coating. Aerosol filtration efficiency decreases upon exposure to ethanol (solvent for dip-coating), but increases with addition of Cu@ZIF-8 NWs. Cu@ZIF-8 NWs shows enhanced antibacterial activity, compared to Cu NWs or ZIF-8 alone, against Streptococcus mutans and Escherichia coli. Antiviral activity against SARS-CoV-2 is assayed using virus-infected Vero E6 cells, demonstrating 55% inhibition of virus replication after 48 h by 1 µg of Cu@ZIF-8 NWs per well. Cu@ZIF-8 NWs' cytotoxicity is tested against four cell lines, and their effect on inflammatory response in A549 cells is examined, demonstrating good biocompatibility. This low-cost, scalable synthesis and straightforward deposition of Cu@ZIF-8 NWs onto filter media has great potential to reduce disease transmission, resource consumption, and environmental impact of waste.

Bio-functional properties of probiotic Lactobacillus: current applications and research perspectives.

Lactic acid bacteria as a starter culture are very important component in the fermentation process of dairy and food industry. Application of lactic acid bacteria as probiotic bacteria adds more functionality to the developed product. Gut colonizing bacteria have attractive benefits related to human health. Bio-functional properties such as antimicrobial activity, anti-inflammatory, ACE-inhibitory, antioxidant, antidiarrheal, antiviral, immunomodulatory, hypocholesterolemic, anti-diabetic and anti-cancer activities are the most applicable research areas of lactic acid bacteria. Different strains of Lactobacillus are generally consumed as probiotics and colonize the gastrointestinal tract. Sometimes these bacteria may possess antimicrobial activity and may positively influence the effect of antibiotics. Use of Lactobacillus spp. for the development of functional foods is one of the promising areas of current research and applications. Individual bacterial species have unique biological activity, which may vary from strains to strains and identification of this uniqueness could be helpful in the development of functional and therapeutic food products.

Quantification of field-incurred residues of cyantraniliprole and IN-J9Z38 in cabbage/soil using QuEChERS/HPLC-PDA and dietary risk assessment.

Cyantraniliprole is an anthranilic diamide insecticide used for the effective management of diamondback moth in cabbage. Dietary risk assessment of pesticides in food is a major concern now. This study developed a QuEChERS/HPLC-PDA-based highly efficient and reliable method, registering 89.80-100.11% recoveries of cyantraniliprole and its metabolite IN-J9Z38 from cabbage and soil with a relative standard deviation of 0.43-5.77%. Field experiment was conducted to study the residue dissipation of cyantraniliprole in cabbage and soil. Two foliar treatments of 10.26% formulation (Benevia) at 60 (T1 ) and 120 (T2 ) gram active ingredient/hectare were applied. The dissipation half-lives of cyantraniliprole in cabbage and soil were determined to be 3.5-4.2 and 3.8-5.3 days at T1 and 3.9-4.8 and 4.1-4.7 days at T2 , respectively. The maximum concentrations of IN-J9Z38 at T1 and T2 were 0.819 and 1.061 mg/kg, respectively, on the fifth day. A risk quotient value of <1 indicates no dietary risk to the consumers. The residues in the harvested cabbage were below the tolerance level of 2.0 mg/kg established by the regulatory body in India.

Imidazopyridazine Acetylcholinesterase Inhibitors Display Potent Anti-Proliferative Effects in the Human Neuroblastoma Cell-Line, IMR-32.

Imidazo[1,2-b]pyridazine compounds are a new class of promising lead molecules to which we have incorporated polar nitro and amino moieties to increase the scope of their biological activity. Two of these substituted 3-nitro-6-amino-imidazo[1,2-b]pyridazine compounds (5c and 5h) showed potent acetylcholinesterase (AChE) inhibitory activity (IC50 40-50 nM), which we have previously reported. In this study, we wanted to test the biological efficacy of these compounds. Cytotoxicity assays showed that compound 5h mediated greater cell death with over 43% of cells dead at 100 µM and activation of caspase 3-mediated apoptosis. On the other hand, compound 5c mediated a dose-dependent decrease in cell proliferation. Both compounds showed cell cycle arrest in the G0/G1 phase and reduced cellular ATP levels leading to activation of adenosine monophosphate-activated protein kinase (AMPK) and enhanced mitochondrial oxidative stress. It has to be noted that all these effects were observed at doses beyond 10 µM, 200-fold above the IC50 for AChE inhibition. Both compounds also inhibited bacterial lipopolysaccharide-mediated cyclooxygenase-2 and nitric oxide release in primary rat microglial cells. These results suggested that the substituted imidazo (1,2-b) pyridazine compounds, which have potent AChE inhibitory activity, were also capable of antiproliferative, anti-migratory, and anti-inflammatory effects at higher doses.

Stimuli Responsive In Situ Gelling Systems Loaded with PLGA Nanoparticles of Moxifloxacin Hydrochloride for Effective Treatment of Periodontitis.

The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1 week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1 week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3 weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment.

Design of expert guided investigation of native L-asparaginase encapsulated long-acting cross-linker-free poly (lactic-co-glycolic) acid nanoformulation in an Ehrlich ascites tumor model.

Present study explores native L-asparaginase encapsulated long-acting cross-linker-free PLGA-nanoformulation in an Ehrlich ascites tumor model. L-asparaginase-PLGA nanoparticles for tumor were prepared using a double emulsion solvent evaporation technique, optimized and validated by Box-Behnken Design. L-ASN-PNs showed a particle size of 195 nm ± 0.2 nm and a PDI of 0.2. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) techniques revealed its smooth morphology and elicited an in-vitro release of 80% of the drug, following the Higuchi drug release model. In-vivo studies of L-ASN-PNs on an Ehrlich ascites tumor (EAT) model were completed and compared with the standard medication of 5-fluorouracil (5-FU) treatment. L-ASN-PN treated mice showed a 51.15% decrease in tumor volume and 100% survival rate with no reduction in body weight, no haemotoxicity and no hepatotoxicity, as evident from the hematological parameters, and liver enzyme parameters that were well within the prescribed limits. Chemotherapy has severe side effects and restricted therapeutic success. Henceforth, the purported L-Asparaginase PLGA nanoparticles are a suitable entity for better tumor regression, intra-tumor accumulation and no hematological side-effects.