Impact of HPV strains on molecular mechanisms of cervix cancer.

PURPOSE: Cervical cancer accounts for a high number of deaths worldwide. Risk factors are extensive for cervix cancer but Human papillomavirus (HPV) plays a prime role in its development. Different strains of HPV are prevalent globally, which show different grades of mortality and morbidity among women. This study is planned to evaluate the molecular mechanism of different strains of HPV infection and progression leading to cervix cancer. METHODS: This review includes different research articles on cervix cancer progression reported from India and all over the world. RESULTS: HPV 16 and 18 are prevalent strains using heparan sulfate-independent and dependent pathways for viral replication inside the cell. It also uses transcription mechanisms through NF-kappa B, FOXA-1, and AP-1 genes while strains like HPV-35, 45, and 52 are also predominant in India, which showed a very slow mechanism of progression due to which mortality rate is low after their infection with these strains. CONCLUSION: HPV uses E6 and E7 proteins which activate NF-kappa B and AP-1 pathway which suppresses the tumor suppressor gene and activates cytokine production, causing inflammation and leading to a decrease in apoptosis due to Caspase-3 activation. In contrast, the E7 protein involves HOXA genes and decreases apoptotic factors due to which mortality and incidence rates are low in viruses that use E7 motifs. Some HPV strains employ the cap-dependent pathway, which is also associated with lower mortality and infection rates.

Photophysical Study of Heteroatom-Doped Carbon Dots-MnO2-Based Nanosensor: Selective Detection of Glutathione in the Nanomolar Level.

Heteroatom doping on carbon dots (Cdots) has been developed as an efficient approach to modify its optical and electronic properties. The four different types of heteroatom-doped Cdots (undoped Cdots (u-Cdots, nitrogen-doped Cdots (N-Cdots), sulfur-doped Cdots (Cdots), nitrogen, sulfur codoped Cdots (N, S-Cdots)) have been synthesized through a simple heat treatment of 5 min. Among four different heteroatoms doped nanosensors, N, S-Cdots with MnO2 nanospheres (Mn NS) showed one of the best fluorescents "on-off-on" nanosensors for selective sensing of glutathione (GSH) and cell imaging. N, S-Cdots showed a high fluorescence quantum yield, good photostability, ionic strength, and pH stability. N, S-Cdots with Mn NS demonstrated extremely high fluorescence quenching efficiency and the maximum fluorescence recovery rate after adding GSH to the produced solution. The photophysical study of N, S-Cdots-Mn NS used as a sensor confirms the inner filter effect (IFE) quenching mechanism between them. The developed sensor has an 80 nM limit of detection (LOD) for GSH. The heteroatom-doped framework of Cdots plays a significant role in the sensitive detection of GSH. N, S-Cdots-Mn NS have good permeability, biocompatibility, and low toxicity, due to which it was used in the intracellular imaging of GSH in living cells. The prepared sensor is rapid, economical, less toxic, and highly applicable in diagnosing diseases.

Targeted drug delivery using beeswax-derived albendazole-loaded solid lipid nanoparticles in Haemonchus contortus, an albendazole-tolerant nematode.

Targeted delivery has not been achieved for anthelmintic treatment, resulting in the requirement of excess drug dose leading to side effects and therapeutic resistance. Gastrointestinal helminths take up lipid droplets from digestive fluid for energy production, egg development, and defense which inspired us to develop biocompatible and orally administrable albendazole-loaded solid lipid nanoparticles (SLN-A) that were derived from beeswax and showed drug loading efficiency of 83.3 ± 6.5 mg/g and sustained-release properties with 84.8 ± 2.5% of drug released at pH 6.4 within 24 h at 37 °C. Rhodamine B-loaded SLN showed time-dependent release and distribution of dye in-vitro in Haemonchus contortus. The sustained-release property was shown by the particles that caused enhancement of albendazole potency up to 50 folds. Therefore, this formulation has immense potential as an anthelminthic drug delivery vehicle that will be able to reduce the dose and drug-induced side effects by enhancing the bioavailability of the drug.

Formulation and evaluation of solid lipid nanoparticles loaded with papaya seed chloroform extract for long-term antifertility effects on the male rat, Bandicota bengalensis.

The study is the first to formulate and investigate potential of papaya seed chloroform extract based solid lipid nanoparticles (PSCEN) as antifertility agents on male Bandicota bengalensis. The prepared nanoparticles were spherical of size 300-600 nm. The release kinetics showed a controlled release of the drug with major release over 48 h. To assess the antifertility effects of PSCEN, adult male rats were fed a diet containing two different concentrations of PSCEN (5% and 10%) for 15 days under bi-choice conditions. The mean total active ingredient ingestion of the rats in the two treated groups ranged from 2.13-3.31 and 3.92-5.87 g/100g body weight, respectively. No adverse effects of treatment on body weight were observed. Also, no mortality of rats was observed. The treatment had a significant effect on the weight of the testis and the epididymis, but not on the other organs. Sperm motility (%), sperm viability (%), sperm count (millions/ml), sperm mitochondrial activity (%), sperm nuclear chromatin de-condensation (%) and sperm hypo-osmotic swelling (%) were significantly decreased, and sperm abnormality (%) significantly increased compared to the vehicle control group. The reproductive success rates of male rats treated with 5% and 10% PSCEN and mated with untreated female rats were 20.00-66.67% and 16.67%, respectively, while in untreated female rats mated with male rats of vehicle control group, reproductive success rate was 33.33 to 80%. The study found a maximal antifertility effect of the 10% PSCEN containing bait, which was irreversible up to 105 days after stopping treatment, suggesting long-term efficacy.

Targeting the nervous system of the parasitic worm, Haemonchus contortus with quercetin.

Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary medications lead to a pressing need to develop new anthelmintic drugs and drug targets. However, little understanding of worms' physiology has substantially delayed the process. Here, we are reporting the tissue morphology of Haemonchus contortus, intestinal parasitic helminths found in small ruminants, and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of H. contortus. Further, histological analysis demonstrated damage to various body parts, including isthmus, brut, pseudocoele, and other organs. Mechanistic studies revealed the generation of oxidative stress and alterations in the activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of reactive oxygen species (ROS) generated due to quercetin treatment disclosed neuropils as the primary targets of quercetin in adult worms, which eventually lead to the paralysis and death of the worms. Thus, this work demonstrates that the nervous system of the parasitic helminth, H. contortus, is a novel target of the drug quercetin.

Insulin-copper quantum clusters preparation and receptor targeted bioimaging.

Protein embedded fluorescence quantum clusters (QCs) have received a great amount of interest among the researchers because of their high aqueous solubility, stability, cost efficiency, and target specificity. Considerable advancement has happened in making functional quantum clusters with target specificity. This work reports the simple synthesis of insulin protected copper quantum clusters (ICuQCs) and its receptor-targeted bioimaging applications. The preparation of copper quantum clusters (CuQCs) was done simply by one-pot synthesis method by changing the pH of the insulin protein firstly to 10.5 basic pH than physiological pH. At physiological pH, the mixture incubated in oven 37 °C at 240 rpm has been developed to process initially polydisperse, non-fluorescent, and unstable CuDs into monodispersed (∼2-3 nm), highly fluorescent, and extremely stable ICuQCs in the same phase (aqueous) using insulin as protein. HRTEM image show uniform distribution of CuDs within the protein matrix. Metal ion binding site prediction and docking server (MIB) results show that chain B of insulin contains 3 templates contains 5 amino acid residues which bind with Cu2+ metal ion. Groove 1 contains GLY8 and HIS10 bind has the highest binding potential towards Cu metal ions. The methodology adopted in this study should largely contribute to the practical applications of this new class of QCs. In view of the protein protection, coupled with direct synthesis and easy functionalization, this hybrid QC-protein system is expected to have numerous optical and bioimaging applications in the future.