Exploring the potential of P-glycoprotein inhibitors in the targeted delivery of anti-cancer drugs: A comprehensive review.

Due to the high prevalence of cancer, progress in the management of cancer is the need of the hour. Most cancer patients develop chemotherapeutic drug resistance, and many remain insidious due to overexpression of Multidrug Resistance Protein 1 (MDR1), also known as Permeability-glycoprotein (P-gp) or ABCB1 transporter (ATP-binding cassette subfamily B member 1). P-gp, a transmembrane protein that protects vital organs from outside chemicals, expels medications from malignant cells. The blood-brain barrier (BBB), gastrointestinal tract (GIT), kidneys, liver, pancreas, and cancer cells overexpress P-gp on their apical surfaces, making treatment inefficient and resistant. Compounds that compete with anticancer medicines for transportation or directly inhibit P-gp may overcome biological barriers. Developing nanotechnology-based formulations may help overcome P-gp-mediated efflux and improve bioavailability and cell chemotherapeutic agent accumulation. Nanocarriers transport pharmaceuticals via receptor-mediated endocytosis, unlike passive diffusion, which bypasses ABCB1. Anticancer drugs and P-gp inhibitors in nanocarriers may synergistically increase drug accumulation and chemotherapeutic agent toxicity. The projection of desirable binding and effect may be procured initially by molecular docking of the inhibitor with P-gp, enabling the reduction of preliminary trials in formulation development. Here, P-gp-mediated efflux and several possible outcomes to overcome the problems associated with currently prevalent cancer treatments are highlighted.

Aggregation-induced Emission Active Naphthalimide Derived Schiff Base for Detecting Cu2+ and Its Applications.

Herein, an aggregation-induced emission (AIE) active Schiff base (NHS) was synthesized by condensing naphthalimide hydrazide with salicylaldehyde. The non-fluorescent solution of NHS in DMSO turned to emissive NHS upon increasing the HEPES fraction in DMSO from 70 to 95%. The UV-Vis absorption and DLS studies supported the self-aggregation of NHS that restricted the intramolecular rotation and activated the ESIPT process. The blue fluorescence of AIE luminogen NHS in DMSO:HEPES (5:95, v/v, pH = 7.4) was examined by adding different metal ions (Al3+, Ca2+, Cd2+, Co2+, Cu2+, Cr2+, Fe2+, Fe3+, Hg2+, Mg2+, Mn2+, Ni2+, Pb2+ and Zn2+). NHS showed a selective fluorescence switch-off response for Cu2+ due to the chelation enhancement quenching effect (CHEQ). The quenching of NHS by Cu2+ was explored by using density functional theory (DFT) and Stern-Volmer plot. The practical utility of NHS was examined by quantitative and qualitative analysis of Cu2+ in real water samples.

Fluorescence Sensing of pH and p-Nitrophenol Using an AIEE Active Pyridoxal Derived Schiff Base.

An easy-to-prepare aggregation-induced emission enhancement (AIEE) active Schiff base NPY was synthesized by condensing vitamin B6 cofactor pyridoxal with 3-hydroxy-2-naphthoic hydrazide, and employed for the fluorescent sensing of pH and p-nitrophenol (p-NP). The AIEE phenomenon of NPY was investigated in mixed DMSO/H2O medium. The weakly yellow-fluorescent NPY (λem = 535 nm) in pure DMSO turned to a bright cyan-fluorescent NPY (λem = 490 nm) upon addition of poor solvent water. The DLS and SEM analyses supported the self-aggregation of NPY that restricted the intramolecular rotation and activated the excited state intramolecular proton transfer (ESIPT) process. The AIEE luminogen (AIEEgen) NPY containing 90% of water fraction (fwater) was employed for the fluorescent sensing of pH. AIEEgen NPY displays three distinct fluorescent pH windows: non-fluorescent below pH 3.0 and above pH 10.0, cyan fluorescent between pH 3.0 to 8.0, and yellow fluorescent between pH 8.0 to 10.0. AIEEgen NPY was also applied for the detection of nitroaromatics in HEPES buffer (10% DMSO, 10 mM, pH 7.0). The addition of p-NP selectively quenched the fluorescent intensity of AIEEgen NPY with an estimated detection limit of 1.73 µM. The analytical utility of AIEEgen NPY was examined by quantifying p-NP in different real water samples.

Pyridoxal Derived AIEgen for Fluorescence Turn-off Sensing of Cu2+ and Fe2+ Ions and Fluorescence Imaging of Latent Fingerprints.

Schiff base 4-((E)-((E)-(2-hydroxybenzylidene)hydrazono)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (HSP) was synthesized by condensing vitamin B6 cofactor pyridoxal with salicylaldehyde hydrazone, and characterized by standard spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and ESI-MS). The solution of HSP in DMSO/HEPES (10 mM, pH = 7.4) mixed solvents with varying HEPES fractions (fw) from 0 to 95% showed aggregation-induced emission (AIE). The AIE active HSP in 95% HEPES gave intense fluorescent emission at 570 nm was employed for the detection of metal ions. The fluorescence of HSP was quenched upon adding Cu2+ and Fe2+ ions. The association constant (Ka) of the Schiff base HSP with Cu2+ and Fe2+ ions was estimated as 4.08 × 105 M-1 and 1.23 × 105 M-1, respectively by using the online analysis tool BindFit v0.5. The HSP showed the detection limit down to 1.75 µM and 1.89 µM for Cu2+ and Fe2+ ions, respectively. Further, the aggregates of HSP were applied to visualize latent fingerprints (LFPs) over a non-porous glass slide.

Probing Biothiols Using a Red-Emitting Pyridoxal Derivative by Adopting Copper(II) Displacement Approach and Cell Imaging.

An aggregation-induced emission (AIE) active Schiff base L was obtained by reacting pyridoxal and 2-hydroxy-1-naphthaldehyde with p-phenylenediamine in two simple steps. The colorimetric, UV/VIS and fluorescence studies of L revealed that the yellow emissive L (λem =540 nm, λex =450 nm) in pure DMSO turned to a red-emissive L, when the poor solvent fraction (HEPES buffer, 10 mM, pH 7.4) was increased above 50 % in DMSO. The SEM and DLS results indicated the formation of self-aggregates of L that restricted the intramolecular motion and promoted the excited state intramolecular proton transfer (ESIPT) process. The cations sensing ability of the AIEgen L was explored in HEPES buffer (5 % DMSO, 10 mM, pH 7.4), where Cu2+ selectively quenched the fluorescence at 608 nm due to the chelation-enhanced fluorescence quenching (CHEQ) effect with an estimated sensitivity limit of 0.9 µM. Subsequently, the in situ formed AIEgen L-Cu2+ complex was applied for the cascade detection of glutathione (GSH), cysteine (Cys) and homocysteine (Hcy). The decomplexation of Cu2+ from the AIEgen L-Cu2+ by GSH, Cys and Hcy restored the quenched fluorescence emission of AIEgen L at 608 nm. With this Cu2+ displacement approach, the concentration of Cys, Hcy and GSH can be detected down to 2.8 µM, 3.12 µM and 2.0 µM, respectively. The practical utility of AIEgen L and AIEgen L-Cu2+ was examined by monitoring the selective analytes in real environmental and biological samples, and also applied successfully for the cell imaging applications.

Progressing dementia risk reduction initiatives for culturally and linguistically diverse older adults in Australia.

OBJECTIVES: Dementia is a global public health concern, with approximately 487,500 Australians living with this condition. As an incurable disease, collaborative public health approaches are at the forefront for risk reduction of dementia. In Australia, nearly one in three individuals older than 65 years belong to culturally and linguistically diverse populations (CALD), yet dementia prevention approaches within CALD communities remain limited. Current health services and education require a targeted multidimensional and multicultural approach for dementia prevention interventions. METHODS: Recent recognition of gaps in CALD dementia awareness and accessibility has instigated a range of initiatives that address language disparities and dementia literacy within Australia's older population. While these have created pockets of dementia awareness and health promotion, a 'whole of community' and government approach is needed to decrease the recognised modifiable risk factors of dementia. RESULTS: This work serves to identify effective methods to promote dementia risk factor reduction using behaviour change techniques through five key recommendations specific for CALD communities. These suggestions are covered by the need for federal funds to be allocated to specific culturally inclusive initiatives highlighted under primary care, public health, research and community sectors. CONCLUSIONS: Key recommendations are created to address language disparities and dementia literacy in Australia's older population to aid healthy brain ageing for CALD older adults.

Comparative evaluation of zinc oxide-eugenol and zinc oxide with Neem oil in root canal treatment of primary teeth: Split-mouth study with 12 months follow-up.

Background: Various root canal filling materials are used to preserve pulp tissue involved carious the primary tooth. A single material that fulfills all the requirements of an ideal root canal filling material for primary teeth is yet unavailable. Hence, this study was initiated to evaluate clinically and radiographically, the efficacy of two obturating materials - zinc oxide eugenol (ZOE) and zinc oxide mixed with Neem oil (ZON) for 12 months. Aims: To assess the success rate of a mixture of zinc oxide and neem oil in comparison to zinc oxide-eugenol paste, as an obturating material in primary molars. To compare the efficacy of ZON as an obturating material at the various time interval of 3, 6, 9, and 12 months postoperatively. Materials and methods: This split-mouth, double-blind study was performed on 24 children aged 5-7 years, who presented with bilaterally infected primary molars. Total 48 infected primary molars were divided into two groups for pulpectomy followed by obturation with ZOE and ZON, respectively. Randomization with the chit-pick method, for the control and experimental drug, was performed. A follow-up for 12 months was performed. The Chi-square test was used for inter-group comparison and the Z test was used for the analysis of data over a period of time. Results: Overall clinical findings in this study revealed 91.7% results in ZOE compared with 100% results in the ZON group. The radiographical findings revealed 91.7% results in ZOE compared with 100% success in the ZON group. Conclusion: ZON demonstrated excellent effectiveness as an obturating material in the 12-month follow-up period as compared to ZOE in primary teeth. The efficacy elicited in this study could be a basis to recommend ZON as herbal alternative obturation material.

Occlusal Traits of Primary Dentition among Pre-School Children of Mehsana District, North Gujarat, India.

INTRODUCTION: Aesthetic and functional problems in the dentofacial complex among children are often attributed to the disturbances in the dentofacial growth and development. This can be recognized during routine dental visits. This study pursued to assess the occlusion of the primary dentition in three to five-year-old children. AIM: To study the occlusal traits of the primary dentition in a group of three to five-year-old North Gujarat children of Mehsana district and the variation in their occlusion relative to age and gender in the same group. MATERIALS AND METHODS: The study was a cross-sectional survey based on clinical examination and photographic evaluation of the primary dentition, 383 preschool children aged three to five years who were randomly selected from preschools in Mehsana district, Gujarat, India, using a multistage sampling technique. The study group was evaluated for the several occlusal parameters that include primary molar relation based on Baume classification and canine relation, overjet, overbite were assessed using Foster and Hamilton criteria. Chi-square test was performed to carry out statistical analysis. The p-value<0.05 was taken as statistically significant. RESULTS: Out of 383 participants, 55.35% had flush terminal plane; 43.34% mesial step molar relationship and 1.31% distal step molar relationship, 63.2% had straight profile, 95.8% had Class I canine relationship, 71.3% primate spaces, 56.7% physiologic spaces. Flush terminal plane was common at three years while, mesial step at four to five years, and Class I canine relationship was prevalent in both age groups. Flush terminal plane was more common in female participants than the males. Amongst other occlusal characteristics, increased overbite and open bite were prevalent. CONCLUSION: It was found that the flush terminal plane molar relationship, straight profile, Class I canine relationship, primate spacing, increased overbite and open bite predominated.