Assessment of hematological and biochemical alterations as markers in an Indian major carp Catla catla exposed to various concentrations of zinc oxide nanoparticles

Fingerlings of Catla catla were exposed to 1, 5, and 25 mg/L of zinc oxide nanoparticles (ZnO NPs) for 15 days, and specific hematological and biochemical parameters were evaluated to assess the toxicity. During the exposure period, red blood cell (RBC) count was found to decrease (except at the end of the 5th day in 1 mg/L) whereas white blood cell (WBC) count was found to increase in ZnO NPs treated fishes. A significantly higher hematocrit (Hct) level was recorded in fish exposed to 1 mg/L when compared with control and a higher concentration of ZnO NPs (5 and 25 mg/L). Erythrocyte indices such as mean cellular volume (MCV) and mean cellular hemoglobin (MCH) values (except at the end of 5 and 10th day at 1 and 10 mg/L exposed groups) were significantly increased. Mean cellular hemoglobin concentration (MCHC) level was found to be increased at 1 and 25 mg/L treated groups compared to 10 mg/L. Compared to the control group, plasma glucose level was increased significantly in fish exposed to 5 and 25 mg/L concentrations of ZnO NPs, while the plasma glucose level was decreased at the end of the 15th day in all the concentrations. Plasma protein level was increased at the end of the 5th day while the level of plasma protein was decreased on the 10 and 15th day. A significant increase in glutamate oxaloacetate transaminase (GOT) (except at the end of 10th day) and glutamate pyruvate transaminase (GPT) activity in gill and liver (except at the end of 10 and 15th day in gill) were noted in all the concentrations tested when compared to control groups. The results of the present study indicate that ZnO NPs at 1, 5, and 25 mg/L can alter the hematological and biochemical parameters of fish and the toxicity data may provide the ecotoxicological impact of ZnO NPs on the aquatic environment.

DEVELOPMENT AND CHARACTERIZATION OF TACROLIMUS TABLET FORMULATIONS FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to prepare and characterize inclusion complexes of tacrolimus with β-cyclodextrin to improve its solubility and to formulate them into sublingual fast disintegrating tablets with a view to bypass the first-pass metabolism. Methods: Tacrolimus: β-cyclodextrin inclusion complexes (1:1 and 1:2 molar proportions) were prepared using the kneading method. Their characterization was accomplished by determining the drug content, solubility, Attenuated Total Reflection-Infrared Spectroscopy (ATR-IR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction analysis (pXRD). These were then formulated to fast disintegrating tablets and evaluated for precompression as well as post compressional characteristics. Results: SEM analysis showed the inclusion complexes as rough, non-porous, irregular surfaced aggregate particles. DSC and pXRD analyses confirm the crystallinity change and partial conversion to the amorphous form of the drug in the inclusion complexes. From the solubility studies, it was observed that both the inclusion complexes of 1:2 molar ratio (14.82±0.889 µg/ml) and 1:1 molar ratio (12.72±0.1004 µg/ml) improved the aqueous solubility to greater extents in comparison to that of the pure drug (3.05±0.121 µg/ml). All the tablet formulations showed good precompression and mechanical properties. The inclusion complex loaded tablets exhibited a superior drug release pattern when compared to tablets prepared with tacrolimus alone. The optimized formulation (TT3) showed an in vitro disintegration time of 34.33 s and a percent drug release of 97.87. Conclusion: The inclusion complex formulation combined with the sublingual route of administration can be expected to result in an improved bioavailability of tacrolimus by increasing its solubility and bypassing first-pass metabolism

Responses of metabolic enzymes (GOT, GPT and LDH) in an Indian major carp Cirrhinus mrigala exposed to titanium dioxide (TiO2) nanorods under short-term exposure

Titanium dioxide (TiO2) nanoparticles are extensively manufactured due to their potential properties and applications in various fields such as biomedical, electrical and environmental. These particles are likely to reach the aquatic environment and may cause adverse effects on aquatic organisms. In this study, we investigated the effects of different concentrations (1, 50 and 100 mg L-l) of TiO2 nanorods (NRs). The enzymatic activity of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), and lactate dehydrogenase (LDH) was measured in the liver and muscle of an Indian major carp, Cirrhinus mrigala, under short-term exposure (96 h). The synthesised particles were characterized using X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), UV-Vis spectroscopy (UV-Vis) and photoluminescence (PL) techniques before conducting the toxicity assay. The GOT and GPT activities were significantly elevated in both liver and muscle of fish treated with TiO2 nanorods (except 50 mg L-l in muscle for GPT). Similarly, the activity of LDH was also found to be elevated. The findings of the present investigation suggest that TiO2:NRs might have be absorbed, circulated, accumulated in liver and muscles of C. mrigala resulting in alterations in the enzyme activities. The results revealed that TiO2 nanorods induced alterations in GOT, GPT and LDH activities of fish at tested concentrations. The alterations of these enzymatic parameters can be useful for monitoring the environmental contamination of titanium dioxide (TiO2) nanoparticles in freshwater ecosystem

A Rising Cancer Prevention Target of RSK2 in Human Skin Cancer

RSK2 is a p90 ribosomal S6 kinase family (p90RSK) member regulating cell proliferation and transformation induced by tumor promoters such as epithelial growth factor (EGF) and 12-O-tetradecanoylphorbol 13-acetate (TPA). This family of p90RSK has classified as a serine/threonine kinase that respond to many growth factors, peptide hormones, neurotransmitters, and environmental stresses such as ultraviolet light (UV). Our recent study demonstrates that RSK2 plays a key role in human skin cancer development. Activation of RSK2 by EGF and UV through ERKs signaling pathway induces cell cycle progression, cell proliferation and anchorage-independent cell transformation. Moreover, knockdown of RSK2 by si-RNA or sh-RNA abrogates cell proliferation and cell transformation of non-malignant human skin keratinocyte, and colony growth of malignant melanoma cells in soft agar. Importantly, activated and total RSK2 protein levels are highly detected in human skin cancer tissues including squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Kaempferol and eriodictyol are natural substances to inhibit kinase activity of the RSK2 N-terminal kinase domain, which is a critical kinase domain to transducer their activation signals to the substrates by phosphorylation. In this review, we discuss the role of RSK2 in skin cancer particularly, in activation of signaling pathways and potent natural substances to target RSK2 as chemopreventive and therapeutic agents

Excessive carbohydrate consumption and body mass index: the risk factors for type 2 diabetes mellitus in patients with Prader-Willi syndrome in Tamil Nadu population

Abstract Background Prader-Willi syndrome (PWS) is commonly associated with severe obesity and type 2 diabetes mellitus (T2DM) and is caused by excessive eating. Only very few studies have reported the relationship between excessive eating, weight gain, and T2DM associated with PWS. The aim of the present study was to investigate the relationship between high carbohydrate intake, body mass index (BMI), and the associated risk factor of T2DM development in people with PWS. We collected data from 23 PWS patients along with obesity control (OC) in Tamil Nadu, India. All PWS patients had T2DM whereas only 7 of 23 OC subjects had T2DM. The physical and biochemical parameters were compared in both subjects. We estimated daily intake in grams of food and calories for each item consumed by both PWS and OC subjects (with and without T2DM). Additionally, we compared BMI values and macronutrients, to investigate the occurrence of T2DM in PWS. Results All statistical analyses were done using mean ± SD. PWS subjects showed BMI values that were extremely significant in both adolescent and adult (p value  300 g by PWS patients in Tamil Nadu with BMI ≥ 30 kg/m2 as a risk factor for T2DM. We highly recommend the optimal daily intake of white rice to prevent the development of T2DM in PWS

IMPLEMENTING CENTRAL COMPOSITE DESIGN FOR THE DEVELOPMENT OF TACROLIMUS FILM FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to develop fast-dissolving films (FDFs) of the immunosuppressant drug tacrolimus monohydrate for sublingual administration, employing central composite design (CCD) to improve its bioavailability. Methods: Tacrolimus: β- cyclodextrin inclusion complexes prepared earlier were transformed into FDFs. CCD was used for attaining optimal film formulation with the desired characteristics. The solvent casting method was used for the preparation of films. For optimization, the independent variables selected were the concentration of hydroxy propyl methyl cellulose E5 (HPMC E5) (X1) and concentration of croscarmellose sodium (CCS) (X2) and the responses were disintegration time (Y1) and percentage drug release at 5 minutes (Y2). The suggested optimal films were subjected to further characterization. Results: All the formulations showed good mechanical properties. The composition of optimized FDFconstituted3.016% w/v of HPMC and 11.731%w/wofCCSand its average disintegration time was27.28s and showed 83.13 % mean drug release at 5 minutes. Differential Scanning Calorimetry (DSC) analysis showed complete dispersion and partial conversion into the amorphous form of the drug which was also confirmed by X-ray diffraction (XRD) studies. Scanning Electron Microscopy (SEM) revealed the smooth and porous nature of the film. Conclusion: The developed FDF may be used sublingually for delivering tacrolimus efficiently, avoiding its oral bioavailability problems

Recent advances in radiotherapy and its associated side effects in cancer—a review

Abstract Background Radiotherapy (RT) is the chief nonsurgical method to control malignant tumors. RT has advanced in both methodological and biological aspects over the past few decades. Though RT is a momentous adjuvant non-invasive technique, it leaves behind some unsympathetic effects. Research is going on to surmount these pessimistic sides of RT. Methods We made a mini review of recent articles from the period of 2000 to 2017 regarding radiotherapy and its side effects in various types of cancers. The literature review was done by searching in PUBMED, MEDLINE, and SCOPUS. Results Here, we spotlight the physiological and genetic risks associated with the cancer patients undergoing RT. We illustrated the course of RT in most prevalent cancers tailored with dosage distribution. Radiation-induced mutation in the patients undergoing RT has been shown with evidence. Further, the major drawbacks like the development of radiation resistance in cancerous cells and secondary malignancies have been discussed. The problems associated with radiation dosage in terms of infertility and rejuvenation of reproductive cells has also been discussed. Finally, we discussed the latest treatment stratagem of RT in cancer. Conclusion Cancer treatment will not be accomplished devoid of radiotherapy. But we can brace RT using radiosensitizers and ayurvedic radioprotectors

Neurotoxicity of pesticides – A link to neurodegeneration

Funding Information: The author Dr. VB would like to thank Bharathiar University for providing the necessary infrastructure facility and the Indian Council of Medical Research DHR-GIA [grant number: GIA/2019/000276/PRCGIA], Government of India, New Delhi for providing necessary help in carrying out this review process. Funding Information: This work was supported by the Indian Council of Medical Research DHR-GIA [grant number: GIA/2019/000276/PRCGIA ], and by the Department of Applied Physics, School of Science, Aalto University , Espoo, Finland. Government of India. Publisher Copyright: © 2022Parkinson's disease (PD) is a neurodegenerative disorder which mainly targets motor symptoms such as tremor, rigidity, bradykinesia and postural instability. The physiological changes occur due to dopamine depletion in basal ganglia region of the brain. PD aetiology is not yet elucidated clearly but genetic and environmental factors play a prominent role in disease occurrence. Despite of various environmental factors, pesticides exposure has been convicted as major candidate in PD pathogenesis. Among various pesticides 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely investigated in PD following with paraquat (PQ), maneb (MB), organochlorines (OC) and rotenone. Effect of these pesticides has been suggested to be involved in oxidative stress, alterations in dopamine transporters, mitochondrial dysfunction, α-synuclein (αSyn) fibrillation, and neuroinflammation in PD. The present review discusses the influence of pesticides in neurodegeneration and its related epidemiological studies conducted in PD. Furthermore, we have deliberated the common pesticides involved in PD and its associated genetic alterations and the probable mechanism of them behind PD pathogenesis. Hence, we conclude that pesticides play a prominent role in PD pathogenesis and advance research is needed to investigate the alterations in genetic and mechanistic aspects of PD.Peer reviewe

Chitosan – An alternative drug delivery approach for neurodegenerative diseases

Neurological disorders have become severe and dreadful issues around the globe that are rarely directly mediated because of the blood-brain barrier (BBB). Despite the various therapeutic strategies, including the utilization of cholinesterase inhibitors, metal chelators, molecular chaperones, and anti-body treatment that have been put forth, drug delivery to the brain has remained a problem in the treatment of neurodegenerative disorders (NDD). Chitosan, one of nature's multifunctional polymers, is acknowledged as a useful chemical in the medical and pharmaceutical industries due to its distinctive and flexible biological characteristics. By using Chitosan and its derivatives as drug delivery methods, it is possible to give medications in a sustained and regulated way, increase their stability, and lessen the likelihood of adverse drug reactions. In the current review, we have concentrated on the significance of Chitosan and its derivatives to become a hotspot in drug delivery, particularly for NDDs. This review also explains their properties as drug delivery vectors and their ability to cross the BBB, which is a significant obstacle to medication administration in NDDs. In conclusion, this review suggests that expanding the scope of such research would make it possible to develop NDD drug delivery systems that are more efficient