Remote loading in liposome: a review of current strategies and recent developments.

Liposomes have gained prominence as nanocarriers in drug delivery, and the number of products in the market is increasing steadily, particularly in cancer therapeutics. Remote loading of drugs in liposomes is a significant step in the translation and commercialization of the first liposomal product. Low drug loading and drug leakage from liposomes is a translational hurdle that was effectively circumvented by the remote loading process. Remote loading or active loading could load nearly 100% of the drug, which was not possible with the passive loading procedure. A major drawback of conventional remote loading is that only a very small percentage of the drugs are amenable to this method. Therefore, methods for drug loading are still a problem for several drugs. The loading of multiple drugs in liposomes to improve the efficacy and safety of nanomedicine has gained prominence recently with the introduction of a marketed formulation (Vyxeos) that improves overall survival in acute myeloid leukemia. Different strategies for modifying the remote loading process to overcome the drawbacks of the conventional method are discussed here. The review aims to discuss the latest developments in remote loading technology and its implications in liposomal drug delivery.

2,4-Dihydroxycinnamic acid as spike ACE2 inhibitor and apigenin as RdRp inhibitor in Nimbamritadi Panchatiktam Kashayam against COVID-19: an in silico and in vitro approach.

Nimbamritadi Panchatiktam Kashayam (NPK) is an ayurvedic formulation composed of ingredients with potent anti-viral activities. We studied the interaction energy of 144 phytoconstituents present in NPK against spike receptor-binding domain (RBD) complexed with ACE2 protein (PDB ID: 6LZG) and RNA-dependent RNA polymerase protein (PDB ID: 7BTF) using Biovia Drug Discovery studio. The result indicated that 2,4-hydroxycinnamic acid exerts more significant binding affinities (28.43 kcal/mol) than Umifenovir (21.24 kcal/mol) against spike ACE2. Apigenin exhibited the highest binding affinities (54.63 kcal/mol) compared with Remdesivir (24.52 kcal/mol) against RdRp. An in vitro analysis showed a reduction in the number of lentiviral particles on transfected HEK293T-hACE2 cells as assessed by pseudovirus inhibition assay. At the same time, the tested compounds showed non-toxic up to 100 µg/ml in normal cells by MTT assay. The study highlights the plausible clinical utility of this traditional medicine against SARS CoV2.

Modulation of carcinogenesis with selected GRAS nutraceuticals via Keap1-Nrf2 signaling pathway.

Keap1-Nrf2 is a fundamental signaling cascade known to promote or prevent carcinogenesis. Extensive studies identify the key target of modulatory aspects of Keap1-Nrf2 signaling against cancer. Nutraceuticals are those dietary agents with many health benefits that have immense potential for cancer chemoprevention. The nutritional supplements known as nutraceuticals are found to be one of the most promising chemoprevention agents. Upon investigating the dual nature of Nrf2, it became clear that, in addition to shielding normal cells from numerous stresses, Nrf2 may also promote the growth of tumors. In the present review, we performed a systematic analysis of the role of 12 different nutraceuticals like curcumin, sulforaphane, resveratrol, polyunsaturated fatty acids (PUFA) from fish oil, lycopene, soybean, kaempferol, allicin, thymoquinone, quercetin, gingerol, and piperine in modulating the Nrf2/Keap1 signaling mechanism. Among these, 12 Generally Recognized As Safe (GRAS) certified nutraceuticals, sulforaphane is the most extensively studied compound in modulating Keap1-Nrf signaling. Even though there is much evidence at preclinical levels, further high-quality research is still required to validate the potential role of these nutraceuticals in Keap1-Nrf2 modulation.

Case Report of Primary Synovial Sarcoma of the Thyroid Gland: An Unusual Histology at Atypical Location.

Primary synovial sarcoma of the thyroid gland is extremely rare, aggressive, and has a dismal prognosis. We report the case of a 15-year-old male who presented with a progressively increasing neck mass, which was excised and the histopathological and immunohistochemical study suggested biphasic synovial sarcoma of the thyroid gland which was confirmed by synovial sarcoma translocation. There are 14 cases of primary synovial sarcoma of the thyroid reported in the literature so far. This study aimed to document the occurrence of synovial sarcoma histology at an unusual anatomical location with a review of the literature on this rare entity.

Knowledge, Attitude, and Practice of epilepsy in Wayanad, Kerala.

OBJECTIVE: Epilepsy is a common neurological condition characterized by recurrent seizures. The aim of the study was to assess the level of Knowledge, Attitude, and Practices (KAP) in epilepsy in the district of Wayanad. METHODS: This study was conducted among adults residing in Wayanad. This was a community-based door-to-door survey conducted among adults residing in Wayanad District between August 2021 and November 2021. A semi-structured questionnaire was used for data collection. The questionnaire included 23 items that could define the information on the level of knowledge and attitude toward epilepsy. RESULT: A total of 394 subjects without epilepsy were included in this study. According to the results of this study, 68.8% of respondents were female and 85.3% of them had completed at least primary school education. 93.1% of participants had heard about epilepsy and 64.5% of participants were aware that epilepsy was a brain disorder. 30.5% of participants believed that a person with epilepsy could not get married. 73.9% of participants recommended allopathic treatment for epilepsy and only 9.9% of participants knew about surgical treatment option for epilepsy. CONCLUSION: Despite having a good understanding of the disease, there is a general tendency in the population to consider patients with epilepsy as incapable of leading a normal life. The choice of modern treatment methods over traditional is also a positive aspect.

An insight into the role of telmisartan as PPAR-γ/α dual activator in the management of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease. It is rapidly emerging as the frequent cause for liver transplantation with the risk of disease recurrence, even after transplantation. Clinical evidence showed an abnormally altered expression of different peroxisome proliferator-activated receptor (PPAR) isotypes (PPAR-α/γ/δ) in NAFLD with an involvement in the induction of insulin resistance, hepatic steatosis, reactive oxygen species (ROS) formation, and hepatic inflammation. Recently, several dual PPAR-γ/α agonists were developed to simultaneously achieve the insulin-sensitizing effect of PPAR-γ as well as lipid catabolizing effect of PPAR-α. PPAR-α activation could counterbalance the steatogenic and adipogenic effects of PPAR-γ. But most of the drugs were ended in the initial level itself due to harmful adverse effects. In the present review, we discuss the possible mechanism of telmisartan, a typical angiotensin receptor blocker with excellent safety and pharmacokinetic profile, as a PPAR-γ/α dual agonist in the treatment of NAFLD.

Harnessing the immune system against cancer: current immunotherapy approaches and therapeutic targets.

Cancer immunotherapy is a rapidly evolving concept that has been given the tag "fifth pillar" of cancer therapy while radiation therapy, chemotherapy, surgery and targeted therapy remain the other four pillars. This involves the stimulation of the immune system to control tumor growth and it specifically targets the neoplastic cells rather than the normal cells. Conventional chemotherapy has many limitations which include drug resistance, recurrence of cancer and severe adverse effects. Immunology has made major treatment breakthroughs for several cancers such as colorectal cancer, prostate cancer, breast cancer, lung cancer, liver cancer, kidney cancer, stomach cancer, acute lymphoblastic leukaemia etc. Currently, therapeutic strategies harnessing the immune system involve Checkpoint inhibitors, Chimeric antigen receptor T cells (CAR T cells), Monoclonal antibodies, Cancer vaccines, Cytokines, Radio-immunotherapy and Oncolytic virus therapy. The molecular characterization of several tumor antigens (TA) indicates that these TA can be utilized as promising candidates in cancer immunotherapy strategies. Here in this review, we highlight and summarize the different categories of emerging cancer immunotherapies along with the immunologically recognized tumor antigens involved in the tumor microenvironment.

A comprehensive review on tannase: Microbes associated production of tannase exploiting tannin rich agro-industrial wastes with special reference to its potential environmental and industrial applications.

Microorganisms have been used for the production of various enzymes, including inducible tannase for various industrial and environmental applications. Tannases have lot of potential to convert hydrolysable tannins to gallic acid, which is one of the important industrial and therapeutic significant molecules whose demand is over 10000 tons per year. Tannins invariably occur in angiosperms, gymnosperms and pteridophytes, and predominantly present in various parts of plants such as, leaves, roots, bark and fruit. Furthermore, tannery effluents are frequently loaded with significant levels of tannic acid. Tannase can be effectively used to decrease tannin load in the toxic tannery effluent thus providing the opportunity to minimize the operational cost. Over the past three decades, tannase from microbial sources has been proposed for the degradation of natural tannins. The availability of various agro-industrial residues paves a way for maximum utilization of tannase production for the degradation of tannin and eventually the production of gallic acid. In this review, an illustrative and comprehensive account on tannase from microbial source for current day applications is presented. The present review emphasises on up-to-date microbial sources of tannases, biochemical properties, optimization of tannase production in solid state and submerged fermentation and its industrial and environmental applications.

Exploring the physical and quality attributes of muffins incorporated with microencapsulated squalene as a functional food additive.

Squalene, a triterpenoid compound is proven to possess immense bioactivities by virtue of its high antioxidant activity. The present study was designed to investigate the quality attributes of muffins as influenced by addition of encapsulated squalene. Nutritional analysis showed that calorific value of prepared muffins has ranged from 480.78 ± 0.10 to 501.61 ± 0.38 kcal. Baking loss was lowest in case of muffins prepared with encapsulated squalene with its crumb region recorded higher moisture content. Color kinetics study indicated that browning index (BI) was higher in crust portion of encapsulated squalene enriched muffins. Scanning electron micrographs showing that muffins with encapsulated squalene had stronger structural organization. This was further supported by the textural studies showed that the muffins with encapsulated squalene was cohesive, springier and chewy with less gumminess and stiffness indicating their efficacy in improving the textural quality. Oxidative stability and microbiological quality were also high in squalene enriched foods suggesting that squalene might have some antimicrobial effects. Outcome of the study indicated that encapsulated squalene can be very well utilised as a functional food ingredient in ready -to-eat functional foods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s13197-020-04955-9).

Inevitable role of TGF-ß1 in progression of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a major health concern and the most commonly diagnosed chronic liver manifestation among 25% worldwide population. Obesity, insulin resistance, accumulation of toxic lipid free radicals, generation of oxidative stress, overconsumption of fat containing dietary meals and lack of exercise are the paramount factors accountable for the development of NAFLD. During NAFLD, increased oxidative stress and production of enormous number of toxic free radicals activates a number of pro-inflammatory and inflammatory pathways. TGF-ß signaling mechanisms play a central role in maintaining the normal homeostasis of liver. TGF-ß1, one of the three isoforms of TGF-ß family has significant role in different stages of chronic liver conditions. TGF-ß1 promotes HSC activation and extracellular matrix production (ECM), which further contributes in the progression of NAFLD. In this review, we outline the role of TGF-ß1 in different phases of progressive NAFLD along with the signaling mechanism.

Formation of excited triplet states in naphthalene diimide and perylene diimide derivatives: A detailed theoretical study.

Mechanistic details of the excited triplet state formation upon photoexcitation to the low-lying singlet manifold in naphthalene diimide and perylene diimide derivatives are explored theoretically. Static and dynamic aspects of two singlets (S1 and S2) and six triplets (T1-T6) of these molecules are investigated. Suitable vibronic Hamiltonians are constructed to investigate the internal conversion dynamics in both the singlet and triplet manifolds. Computed singlet-triplet energetics, spin-orbit coupling matrix elements, and intersystem crossing rates strongly suggest an efficient intersystem crossing process involving higher triplet states (T6, T5, and T4). Separate full dimensional quantum wavepacket simulations of singlet and triplet manifolds in the approximate linear vibronic model by assuming initial Franck-Condon conditions are carried out to unravel the internal conversion decay dynamics in the respective manifolds. The obtained diabatic electronic populations and nuclear densities are analyzed to illustrate the triplet generation pathways involving higher triplet states in these molecules.

Effect of Virtual Reality Distraction on Pain and Anxiety During Dental Treatment in 5 to 8 Year Old Children.

OBJECTIVE: This study was aimed at assessing the impact of Virtual Reality (VR) distraction technique on pain and anxiety in 5-8-year-old children, during short invasive dental procedures. STUDY DESIGN: 120 children, aged 5-8 years, scoring less than 25 on the SCARED questionnaire, scheduled to undergo short invasive dental procedures, were randomly divided into a control (without VR distraction) and study group (with VR distraction) of 60 each. State anxiety levels were assessed in the children from both groups using revised version of Modified Child Dental Anxiety Scale, before and after dental treatment. Pain perceived during treatment was assessed using Wong Baker Faces pain rating scale at the end of treatment. Salivary cortisol levels were also assessed before, during and after the dental procedure, in all children. RESULTS: We observed a significant reduction in pain perception and state anxiety in children, using VR distraction (p<0.001, p=0.002). The decrease in salivary cortisol levels was significantly greater in children using VR distraction (p<0.001). CONCLUSION: Virtual Reality distraction can be used as a successful behavior modification method in children undergoing short invasive dental treatments.

Antioxidant, functional properties and amino acid composition of pepsin-derived protein hydrolysates from whole tilapia waste as influenced by pre-processing ice storage.

In recent years, hygienic handling of fishery waste is demanded owing to the fact that the fishery waste is an ideal raw material for the preparation of bioactive compounds. In the present study, the effect of pre-processing storage (at 4 ± 2 °C) of whole tilapia waste (WTW) on the properties of its protein hydrolysate derived using pepsin was evaluated. Fish protein hydrolysates (FPH) were prepared from 0, 24 and 48 h old ice stored WTW and designated as FPH-0, FPH-1, and FPH-2, respectively. Total amino acids, total essential amino acids and total hydrophobic amino acids of FPH samples increased with the storage period of raw material (WTW). Antioxidant activities such as DPPH (2, 2 diphynyl-1-picrylhydrazyl) free radical scavenging activity and ferric reducing power of FPH samples were dose dependent. FPH-0 had better antioxidant properties including linoleic acid peroxidation inhibition activity than FPH-1 and FPH-2. The DNA nicking assay revealed the protective effect of FPH preparations against Fenton's reaction mediated oxidative damage. FPH-2 had better emulsifying properties and foaming stability whereas the FPH-0 had relatively good foaming capacity. SDS-PAGE indicated the presence of peptides ranging from 116 to < 14.4 kDa in FPH-0 and less than 18 kDa in FPH-1 and FPH-2. The present study, clearly demonstrated that whole tilapia waste can effectively be converted to FPH and could be a potential ingredient in functional food and as a rich source of high-quality protein in animal feed formulations.

The regulatory effects of Cissus quadrangularis on some enzymes involved in carbohydrate metabolism in streptozotocin-induced diabetic rats.

CONTEXT: Diabetes mellitus (DM) is probably the single most important metabolic disease and is widely recognized as one of the leading causes of death and disability. Cissus quadrangularis Linn. (Vitaceae) is a medicinal food and is reported to possess hypoglycemic activity. OBJECTIVE: The present study evaluates the effect of ethyl acetate fraction of C. quadrangularis stem (CQSF) on carbohydrate metabolism in hepatic tissues of experimental diabetic rats. The phytochemical compounds present in the CQSF extract were identified by gas chromatography-mass spectrometry (GC-MS) analysis. MATERIALS AND METHODS: Diabetic animals were treated with CQSF (50, 100, and 200 mg/kg body weight) for 45 d. Several indices such as blood glucose, glycated hemoglobin (HbA1c), insulin, liver function tests, hepatic glycogen content, and the activities of carbohydrate-metabolizing enzymes were assayed after 45 d of extract treatment. RESULTS: A pronounced effect was observed with extract doses 100 and 200 mg/kg body weight. CQSF at a dose of 100 mg/kg body weight significantly decreased the altered levels of blood glucose by about 56%. CQSF also modulated the activities of carbohydrate-metabolizing enzymes by significantly increasing the activity of hexokinase (1.9-fold) and pyruvate kinase (2.2-fold) and significantly reducing the activity of glucose-6-phosphatase (41.23%), fructose-1,6-diphosphatase (29.43%), and glycogen phosphorylase (35.07%). GC-MS analysis revealed the presence of 10 chemical constituents, and N-methyl-1-adamantane acetamide was found to be the prevailing compound in the extract. DISCUSSION AND CONCLUSION: The current study suggests the antidiabetic potential of CQSF, mediated through the regulation of carbohydrate metabolic enzyme activities.

Mast cells and the gut-liver Axis: Implications for liver disease progression and therapy.

The role of mast cells, traditionally recognized for their involvement in immediate hypersensitivity reactions, has garnered significant attention in liver diseases. Studies have indicated a notable increase in mast cell counts following hepatic injury, underscoring their potential contribution to liver disorder pathogenesis. Predominantly situated in connective tissue that envelops the hepatic veins, bile ducts, and arteries, mast cells are central to both initiating and perpetuating liver disorders. Additionally, they are crucial for maintaining gastrointestinal barrier function. The gut-liver axis emphasizes the complex, two-way communication between the gut microbiome and the liver. Past research has implicated gut microbiota and their metabolites in the progression of hepatic disorders. This review sheds light on how mast cells are activated in various liver conditions such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, hepatic fibrogenesis, and hepatocellular carcinoma. It also briefly explores the connection between the gut microbiome and mast cell activation in these hepatic conditions.

Role of Culinary Indian Spices in the Regulation of TGF-ß Signaling Pathway in Inflammation-Induced Liver Cancer.

SCOPE: Hepatocellular carcinoma (HCC) results from various etiologies, such as Hepatitis B and C, Alcoholic and Non-alcoholic fatty liver disorders, fibrosis, and cirrhosis. About 80 to 90% of HCC cases possess cirrhosis, which is brought on by persistent liver inflammation. TGF-ß is a multifunctional polypeptide molecule that acts as a pro-fibrogenic marker, inflammatory cytokine, immunosuppressive agent, and pro-carcinogenic growth factor during the progression of HCC. The preclinical and clinical evidence illustrates that TGF-ß can induce epithelial-to-mesenchymal transition, promoting progression and hepatocyte immune evasion. Therefore, targeting the TGF-ß pathway can be a promising therapeutic option against HCC. METHODS AND RESULTS: We carry out a systemic analysis of eight potentially selected culinary Indian spices: Turmeric, Black pepper, Ginger, Garlic, Fenugreek, Red pepper, Clove, Cinnamon, and their bioactives in regulation of the TGF-ß pathway against liver cancer. CONCLUSION: Turmeric and its active constituent, curcumin, possess the highest therapeutic potential in treating inflammation-induced HCC and they also have the maximum number of ongoing in-vivo and in-vitro studies.

Unveiling the role of the Hedgehog signaling pathway in chronic liver disease: Therapeutic insights and strategies.

The Hedgehog (Hh) signaling plays a crucial role in adult liver repair by promoting the expansion and differentiation of hepatic progenitor cells into mature hepatocytes and cholangiocytes. Elevated Hh signaling is associated with severe chronic liver diseases, making Hh inhibitors a promising therapeutic option. Sonidegib and vismodegib, both FDA-approved Smoothened (Smo) inhibitors for basal cell carcinoma (BCC), have shown potential for application in chronic liver disorders based on clinical evidence. We highlight the vital role of the Hh pathway in metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and hepatocellular carcinoma (HCC). Moreover, therapeutic strategies targeting the Hh pathway in chronic liver diseases have been discussed, providing a basis for improving disease management and outcomes.

Plant Extracts and Phytochemicals, a Promising Strategy Against Oral Lichen Planus: A Review on Clinical Trials.

BACKGROUND: Oral lichen planus (OLP) is an autoimmune disease that distress keratinized cells of the oral epithelium. Topical corticosteroids and other potential therapies like immunosuppressives, hydroxychloroquine, azathioprine, mycophenolate, dapsone, retinoids, biologic agents are used for the management of OLP. However, their effectiveness, best dose, duration of treatment and safety remain mostly unidentified. Moreover, recurrence of disease and dose-related side effects are the other issues. OBJECTIVE: The primary objective of the review is to explore the existing clinical trials for the efficacy of phytochemicals in treating OLP in comparison to corticosteroids. A comprehensive information about their mode of action is also discussed. METHODS: We have discussed different clinical trials conducted on various phytochemicals and plant extracts/formulations like curcumin, lycopene, quercetin, glycyrrhizin, purslane, raspberry, aloe vera gel and aloe vera mouthwash for the treatment of OLP. RESULTS: The current therapy for the management of OLP has numerous adverse effects and requires a long-term treatment. Phytochemicals can be a very good alternative in overcoming these side effects and reducing the course of treatment. CONCLUSION: Herbal extracts and their formulations can be an effective alternative to the current therapy due to their proven therapeutic effects, reduced side effects, long-term applicability, prevention of recurrence as well as progression into cancer.

Tumor-Specific Growth Factor (TSGF): A Futuristic Tumor Biomarker in Early Diagnosis of Cancer.

Despite the significant improvement in the treatment modalities, cancer is one of the fastest-growing chronic disease conditions all over the world. Genetic and Epigenetic alterations in the normal physiology of the cell are the key factor for tumor development. These changes can trigger the production of abnormal protein expressions through stimulation of different signaling pathways and can deeply affect normal cell growth and proliferation. Any altered protein expression, genetic variation, micro-RNA or post-translational protein modifications that indicate tumorigenesis can act as an early signal termed as biomarker. Cancer, being a multistep process with accumulating genetic and epigenetic alterations, could be detected early with suitable biomarkers. There are several proteins such as AFP, CA-125, PSA, troponin, CEA, osteopontin, CA 19-9 that act as biomarkers which help in early detection, prognosis, and monitoring of disease progression, a hunt for newer biomarkers with higher specificity and sensitivity is still ongoing. Tumor-specific growth factor (TSGF) is one such budding and prevailing tumor biomarker used for the early-stage detection of several types of carcinomas. TSGF is a gene that helps in tumor angiogenesis and gets released during the preliminary stages from cancer cells that ensure the vascular proliferation of the same. In this review, the clinical investigations of TSGF in different kinds of malignancy is discussed in detail and suggests the possibility of using TSGF as a biomarker in early diagnosis of cancer.

Evaluation of the Nimbamrithadhi Panchathiktha Kashayam against SARS CoV-2 based on Network Pharmacology and Molecular Docking analysis.

BACKGROUND: Nimbamrithadhi Panchathiktha Kashayam (NPK) is an Ayurvedic formulation of potent plant ingredients with immune-modulating effects and anti-viral activities. OBJECTIVES: The present study is intended to identify the key target involved in immune and inflammatory response against SARS-COV-2 via network pharmacology and also investigates the potent phytoconstituent within NPK in combating or modulating target response via molecular docking. METHODS: Active phytoconstituents of NPK were filtered based on overall bioavailability and druglikeness by Lipinski's and ADMETOX prediction. RESULTS: Results indicate that IRF 7 can be selected as an efficient target in regulating immunomodulatory and anti-viral activity via network pharmacology. Molecular docking studies show that apigenin (22.22 Kcal /mol), thiamine (24.89 Kcal /mol) and esculetin (25.21 Kcal /mol) within Nimbamrithadhi Panchathiktha Kashayam(NPK) possess better binding affinity in comparison with standard drug gemcitabine (14.56 Kcal /mol). Even though docking score is more for Esculetin and Thiamine, Apigenin within Solanum Virgianum (Yellow nightshade) and Azadirachta Indica (Neem) is considered as the active phytoconstituent in modulating immune responses and anti-viral activities based on the number and nature of amino acid interaction. CONCLUSION: To the best of our knowledge, no scientific validation has been done on NPK against COVID-19. The study indicates that NPK can be a better alternative prophylaxis strategy against SARS-COV-2 infection if further validated via suitable preclinical studies.