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Neurocognitive Changes in Spinocerebellar Ataxia Type 3: A Systematic Review with a Narrative Design

Yap KH, Kessels RPC, Azmin S, van de Warrenburg B, Mohamed Ibrahim N

Cerebellum, 2021 Jul 07.
PMID: 34231180 DOI: 10.1007/s12311-021-01282-3

Spinocerebellar ataxia type 3 (SCA3), the commonest dominantly inherited ataxia worldwide, is characterized by disruption in the cerebellar-cerebral and striatal-cortical networks. Findings on SCA3-associated cognitive impairments are mixed. The classification models, tests and scoring systems used, language, culture, ataxia severity, and depressive symptoms are all potential confounders in neuropsychological assessments and may have contributed to the heterogeneity of the neurocognitive profile of SCA3. We conducted a systematic review of studies evaluating neurocognitive function in SCA3 patients. Of 1304 articles identified, 15 articles met the eligibility criteria. All articles were of excellent quality according to the National Institutes of Health quality assessment tool for case-control studies. In line with the disrupted cerebellar-cerebral and striatal-cortical networks in SCA3, this systematic review found that the neurocognitive profile of SCA3 is characterized by a core impairment of executive function that affects processes such as nonverbal reasoning, executive aspects of language, and recall. Conversely, neurocognitive domains such as general intelligence, verbal reasoning, semantic aspect of language, attention/processing speed, recognition, and visuospatial perception and construction are relatively preserved. This review highlights the importance of evaluating neurocognitive function in SCA3 patients. Considering the negative impact of cognitive and affective impairment on quality of life, this review points to the profound impairments that existing or future treatments should prioritize.
Fulltext Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions

Roy P, Das S, Auddy RG, Mukherjee A

Int J Nanomedicine, 2014;9:4723-35.
PMID: 25336950 DOI: 10.2147/IJN.S65262

Andrographolide (AG) is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic) acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7 ± 17.17 nm and ζ-potential +34.4 ± 1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery.
Folate-induced nanostructural changes of oligochitosan nanoparticles and their fate of cellular internalization by melanoma

Musalli AH, Talukdar PD, Roy P, Kumar P, Wong TW

Carbohydr Polym, 2020 Sep 15;244:116488.
PMID: 32536388 DOI: 10.1016/j.carbpol.2020.116488

This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluorouracil were synthesized by carbodiimide chemistry and prepared by nanospray drying technique respectively. The cellular internalization profiles of oligochitosan-folate nanoparticles against the human malignant melanoma cell line (SKMEL-28) were evaluated using confocal scanning electron microscopy technique through fluorescence labelling and endocytic inhibition, as a function of nanoparticulate folate content, size, polydispersity index, zeta potential, shape, surface roughness and folate population density. The cytotoxicity and cell cycle arrest characteristics of oligochitosan-folate-carboxymethyl-5-fluorouracil nanoparticles, prepared with an optimal folate content that promoted cellular internalization, were evaluated against the oligochitosan-folate and oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles. The oligochitosan-folate conjugate nanoparticles were endocytosed by melanoma cells via caveolae- and lipid raft-mediated endocytic pathways following them binding to the cell surface folate receptor. Nanoparticles that were larger and with higher folic acid contents and zeta potentials exhibited a higher degree of cellular internalization. Excessive conjugation of nanoparticles with folate resulted in a high nanoparticulate density of folate which hindered nanoparticles-cell interaction via folate receptor binding and reduced cellular internalization of nanoparticles. Conjugating oligochitosan with 20 %w/w folate was favorable for cellular uptake as supported by in silico models. Conjugating of oligochitosan nanoparticles with carboxymethyl-5-fluorouracil and 20 %w/w of folate promoted nanoparticles-folate receptor binding, cellular internalization and cancer cell death via cell cycle arrest at S phase at a lower drug dose than oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles and neat carboxymethyl-5-fluorouracil.
Quercetin-Decorated Curcumin Liposome Design for Cancer Therapy: In-Vitro and In-Vivo Studies

Ravichandiran V, Masilamani K, Senthilnathan B, Maheshwaran A, Wong TW, Roy P

Curr Drug Deliv, 2017;14(8):1053-1059.
PMID: 27572089 DOI: 10.2174/1567201813666160829100453

BACKGROUND: Curcumin is a yellow polyphenolic chemopreventive agent isolated from the rhizomes of Curcuma longa. It is approved as Generally Regarded as Safe by US FDA. Nonetheless, its clinical success is limited due to its poor aqueous solubility, fast metabolism and short biological half-life attributes.
OBJECTIVE: Quercetin-decorated liposomes of curcumin (QCunp) are perceived to be able to overcome these biopharmaceutical drawbacks.
METHODS: Curcumin liposomes with/without quercetin were prepared by lipid hydration technique. The liposomes were characterized for their particle size, zeta potential, surface morphology, drug loading and release characteristics. The toxicity of the liposomes were evaluated in-vitro and their invivo efficacy were tested against Dalton's ascites lymphoma in mice.
RESULTS: Liposomes designed showed particle size of 261.8 ± 2.1 nm with a negative zeta potential of -22.6±1.6 mV. Quercetin decorated liposomes were more effective in increasing the life span and body weight of lymphoma inflicted mice compared to those without quercetin. Similarly, the presence of quercetin also contributed to enhanced cytotoxicity of the liposomal formulation towards HT-29 cells and HCT-15 cells.
CONCLUSION: Newer liposomal design exhibited promising potential to emerge as alternative anticancer therapeutics.
Fulltext Engineered silybin nanoparticles educe efficient control in experimental diabetes

Das S, Roy P, Pal R, Auddy RG, Chakraborti AS, Mukherjee A

PLoS One, 2014;9(7):e101818.
PMID: 24991800 DOI: 10.1371/journal.pone.0101818

Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17 ± 0.01 µg/lit to 0.57 ± 0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.
Functionalized Carbon Nano-scale Drug Delivery Systems From Biowaste Sago Bark For Cancer Cell Imaging

Abdul Manaf SA, Hegde G, Mandal UK, Wui TW, Roy P

Curr Drug Deliv, 2017;14(8):1071-1077.
PMID: 27745545 DOI: 10.2174/1567201813666161017130612

BACKGROUND: Nano-scale carbon systems are emerging alternatives in drug delivery and bioimaging applications of which they gradually replace the quantum dots characterized by toxic heavy metal content in the latter application.
OBJECTIVE: The work intended to use carbon nanospheres synthesized from biowaste Sago bark for cancer cell imaging applications.
METHODS: This study synthesised carbon nanospheres from biowaste Sago bark using a catalyst-free pyrolysis technique. The nanospheres were functionalized with fluorescent dye coumarin-6 for cell imaging. Fluorescent nanosytems were characterized by field emission scanning electron microscopy-energy dispersive X ray, photon correlation spectroscopy and fourier transform infrared spectroscopy techniques.
RESULTS: The average size of carbon nanospheres ranged between 30 and 40 nm with zeta potential of -26.8 ± 1.87 mV. The percentage viability of cancer cells on exposure to nanospheres varied from 91- 89 % for N2a cells and 90-85 % for A-375 cells respectively. Speedy uptake of the fluorescent nanospheres in both N2a and A-375 cells was observed within two hours of exposure.
CONCLUSION: Novel fluorescent carbon nanosystem design following waste-to-wealth approach exhibited promising potential in cancer cell imaging applications.
Fulltext Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita

Roy P, Abdulsalam FI, Pandey DK, Bhattacharjee A, Eruvaram NR, Malik T

Pharmacognosy Res, 2015 Jun;7(Suppl 1):S57-62.
PMID: 26109789 DOI: 10.4103/0974-8490.157997

Swertia cordata and Swertia chirayita are temperate Himalayan medicinal plants used as potent herbal drugs in Indian traditional systems of medicine (Ayurvedic, Unani and Siddha).
Lactoferrin-tethered betulinic acid nanoparticles promote rapid delivery and cell death in triple negative breast and laryngeal cancer cells

Halder A, Jethwa M, Mukherjee P, Ghosh S, Das S, Helal Uddin ABM, et al.

Artif Cells Nanomed Biotechnol, 2020 Nov 17;48(1):1362-1371.
PMID: 33284038 DOI: 10.1080/21691401.2020.1850465

Cancer management presents multifarious problems. Triple negative breast cancer (TNBC) is associated with inaccurate prognosis and limited chemotherapeutic options. Betulinic acid (BA) prevents angiogenesis and causes apoptosis of TNBC cells. NIH recommends BA for rapid access in cancer chemotherapy because of its cell-specific toxicity. BA however faces major challenges in therapeutic practices due to its limited solubility and cellular entree. We report lactoferrin (Lf) attached BA nanoparticles (Lf-BAnp) for rapid delivery in triple negative breast (MDA-MB-231) and laryngeal (HEp-2) cancer cell types. Lf association was confirmed by SDS-PAGE and FT-IR analysis. Average hydrodynamic size of Lf-BAnp was 147.7 ± 6.20 nm with ζ potential of -28.51 ± 3.52 mV. BA entrapment efficiency was 75.38 ± 2.70% and the release mechanism followed non-fickian pattern. Impact of Lf-BAnp on cell cycle and cytotoxicity of triple negative breast cancer and its metastatic site laryngeal cancer cell lines were analyzed. Lf-BAnp demonstrated strong anti-proliferative and cytotoxic effects, along with increased sub-G1 population and reduced number of cells in G1 and G2/M phases of the cell cycle, confirming reduced cell proliferation and significant cell death. Speedy intracellular entry of Lf-BAnp occurred within 30 min. Lf-BAnp design was explored for the first time as safer chemotherapeutic arsenals against complex TNBC conditions.
Fulltext Retraction Note: Weather indicators and improving air quality in association with COVID-19 pandemic in India

Chakrabortty R, Pal SC, Ghosh M, Arabameri A, Saha A, Roy P, et al.

Soft comput, 2023 May 29.
PMID: 37362259 DOI: 10.1007/s00500-023-08596-w

[This retracts the article DOI: 10.1007/s00500-021-06012-9.].
Fulltext Weather indicators and improving air quality in association with COVID-19 pandemic in India

Chakrabortty R, Pal SC, Ghosh M, Arabameri A, Saha A, Roy P, et al.

Soft comput, 2023;27(6):3367-3388.
PMID: 34276248 DOI: 10.1007/s00500-021-06012-9

The COVID-19 pandemic enforced nationwide lockdown, which has restricted human activities from March 24 to May 3, 2020, resulted in an improved air quality across India. The present research investigates the connection between COVID-19 pandemic-imposed lockdown and its relation to the present air quality in India; besides, relationship between climate variables and daily new affected cases of Coronavirus and mortality in India during the this period has also been examined. The selected seven air quality pollutant parameters (PM10, PM2.5, CO, NO2, SO2, NH3, and O3) at 223 monitoring stations and temperature recorded in New Delhi were used to investigate the spatial pattern of air quality throughout the lockdown. The results showed that the air quality has improved across the country and average temperature and maximum temperature were connected to the outbreak of the COVID-19 pandemic. This outcomes indicates that there is no such relation between climatic parameters and outbreak and its associated mortality. This study will assist the policy maker, researcher, urban planner, and health expert to make suitable strategies against the spreading of COVID-19 in India and abroad.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00500-021-06012-9.