The role of mitochondria in the apoptosis signaling cell death pathway is regulated by extrinsic and intrinsic pathway, encompassing multiple components like the Bcl-2 family of proteins, death receptors, caspases, Smac/DIABLO, IAPs, Omi/HtrA2 and cytochrome c. These entities serve as effective molecular targets for numerous drugs targeting mitochondrial apoptotic pathways, mainly emphasizing oncology therapeutics. Defective apoptosis is an acquired hallmark of cancer cells, which promotes the establishment of apoptosis-targeting anti-cancer drugs in cancer treatment. The review provides an overview of the Bcl-2 inhibiting, IAPs antagonizing, caspase inhibiting and BH3 mimicking actions, mediated by anti-cancer drugs, rendering beneficial outcomes in different forms of cancer. The authors elaborate on the significance of synthetic and natural agents, targeting the mitochondrial apoptotic pathway, in ameliorating tumor cell growth in the body, and the specificity and effectiveness of these agents, motivating the researchers to explore mitochondrial apoptosis targeting of anti-tumor drugs of both herbal and synthetic origin. Thus, the review aims to predict this dynamic approach in oncology, simultaneously highlighting the challenges and future prospects, providing an opportunity to the experts to "go over with a fine tooth comb" in understanding this "programmed cell death pathway", and establishing reliability and accuracy of this therapeutic paradigm in the upcoming future.
Abstract: The term “neurodegenerative disorders” refers to a group of illnesses in which deterioration of nerve structure and function is a prominent feature. Cognitive capacities such as memory and decision-making deteriorate as a result of neuronal damage. The primary difficulty that remains is safeguarding neurons since they do not proliferate or regenerate spontaneously and are therefore not substituted by the body after they have been damaged. Millions of individuals throughout the world suffer from neurodegenerative diseases. Various pathways lead to neurodegeneration, including endoplasmic reticulum stress, calcium ion overload, mitochondrial dysfunction, reactive oxygen species generation, and apoptosis. Although different treatments and therapies are available for neuroprotection after a brain injury or damage, the obstacles are inextricably connected. Several studies have revealed the pathogenic effects of hypothermia, different breathed gases, stem cell treatments, mitochondrial transplantation, multi-pharmacological therapy, and other therapies that have improved neurological recovery and survival outcomes after brain damage. The present review highlights the use of therapeutic approaches that can be targeted to develop and understand significant therapies for treating neurodegenerative diseases.
Chlorthalidone nanocrystals were developed via lyophilization with the aid of cryoprotectants. To produce stable and free-flowing chlorthalidone nanocrystals, various cryoprotectants including trehalose, mannitol, sucrose, polyethylene glycol (PEG), glycerol, and glucose were considered, and their impact on the viability and characteristics of the nanocrystals were investigated. This was accomplished by characterizing the nanocrystals by considering different parameters such as particle size, polydispersity index (PDI), surface charge, surface properties, encapsulation efficiency, loading capacity, prolonged stability studies, and subsequent release kinetics. The outcomes of this research revealed that formulation (FC7) containing mannitol as a cryoprotectant in 7.5% concentration during lyophilization (freeze drying) produced an optimized nanocrystal formulation without any change in the structure and characteristics. However, nanocrystals obtained via trehalose, PEG, and sucrose showed some extent of aggregation or agglomeration among the crystals. The particle size and surface charge of the optimized nanocrystals were 118 nm and −28.2 mV, respectively. The in-vitro drug release of chlorthalidone nanocrystals was increased up to 4-fold, approximately (91.6% in 90 minutes) when compared with pure chlorthalidone drug (23.37% in 90 minutes) because of the decrease in particle size, thus may significantly enhance the bioavailability of the drug. The surface morphology of the obtained nanocrystals was determined by SEM, which revealed better consistency of nanocrystals with multispectral results. Moreover, stability studies indicated that the crafted nanocrystals were stable at normal room temperature (25 °C) for 6 months. From the obtained results, it was concluded that the mannitol-like cryoprotectant could be effectively used in the lyophilization process to produce stable and free-flowing nanocrystals loaded with chlorthalidone-like BCS class IV drug moieties.
Traditional system of medicine recommends use of various plants ant its formulations to treat hepatic disorder. In the present study a poly herbal preparation containing methanolic extracts of dried rhizomes of Curcuma longa and dried leaves of Occimum sanctum, Murraya koenigii, and Nyctanthes arbrotristis was developed and explored for its hepatoprotective activity against d-galactosmine induced hepatotoxicity. Polyherbal preparation was administered at doses of 50, 100 and 250 mg/kg p.o. Preparation at dose level of 250mg/kg offered significant hepatoprotective action by reducing serum marker enzymes like ALT, ASP and ALP, total and direct bilirubin. Histopathological studies further confirmed the hepatoprotective activity of the preparation in comparison to d-galactosamine treated groups. The results obtained were compared with sylimarin (100mg/kg p.o.) as the standard drug.
Diabetes retinopathy (DR) is the leading cause of blindness and is considered as the most ordinary microvascular complication of diabetes mellitus (DM). The current available therapies can only be effective in the progressive stages of DR and there are various clinical studies which depicts the inconclusive outcomes of these available therapies after assessing the long-term efficacy and safety of such treatments. Moreover, there is an indispensable need of a more reliable as well as potent treatment which can be considered as more efficacious treatment for the management of DR. The treatment of DR can be possible at the early stages with polyphenols which are plant derived chemical agents and can be act as an alternative to other treatments and can optimistically prevent the further evolution of disease. The present review emphasizes the role of polyphenols on cellular and molecular mechanisms altered by DR in preclinical and clinical studies.
Introduction: India carries the highest burden of anemia, particularly in children and women. Children at the growing stage are at the risk of nutrition depletion, hence anemia. Fewer data are available on the prevalence of anemia in growing children of age 10-14 years. It is important to intervene early and track this group. The objective of the present study was to estimate the prevalence of anemia and its correlation to age, gender and body mass index in children of rural area of Ghaziabad, Uttar Pradesh, India.
Method: Total 600 children of 5-13 years age group were included in this study. A detailed questionnaire was used to collect the health details of the children and socioeconomic status of the parents. Hemoglobin was determined by the calibrated Hemoglobin analyzer. Body mass index values were calculated based on the measurements of weight and height of the children.
Results: Prevalence of anemia as per WHO standards in these children was 57.67%. Results of the study population reveal that anemia in this region is more prevalent in girls (68%) when compared to boys (47.3%). However, association between body mass index and hemoglobin was not statistically significant in the present study.
Conclusions: Our results suggest that increased prevalence of anemia in the children of rural area is associated with multiple nutrient deficiencies. Nutritional interventions, evaluation of predisposing risk factors and increased coverage of supplementation programme are recommended measures that can be adopted to control anemia in children.
Nanosuspension has emerged as an effective, lucrative, and unequalled approach for efficiently elevating the dissolution and bioavailability of aqueous soluble drugs. Diverse challenges persist within this domain, demanding further comprehensive investigation and exploration. This study aims to design, develop, optimise formulation and process variables, and characterise the stabilised aqueous dissolvable nanosuspension using chlorthalidone as a BCS class- IV drug. Nanosuspensions of the chlorthalidone drug were prepared using a combination of topdown and bottom-up approaches. Various polymers such as Pluronic L-64, F-68, F-127, and Synperonic F-108 were used as stabilisers in this research. All important processes and formulation variables, such as ultrasonication intensity and time, the concentration of the drug, organic solvent, and stabilisers that may critically influence the characteristics of the nanosuspensions, were optimised. Formulation screening was performed using the optimisation of process and formulation variables, and the optimised nanosuspension formulation was assessed for particle size, PDI, surface charge, morphology, in vitro drug release, and stability. To select an optimised nanosuspension formulation, the effects of formulation and process variables were investigated. These variables critically influence the development of a stabilised nanosuspension. The outcomes revealed that the nanosuspension formulation containing pluronic F- 68 as a stabiliser in 0.6% w/v concentration and the drug in 4 mg/ml concentration were optimized. The particle size and zeta potential of the optimised preparation were 110 nm and -27.5 mV, respectively. The in-vitro drug release of chlorthalidone drug from the optimised nanoformulation was increased up to 3-fold, approximately (88% in 90 min) compared with pure chlorthalidone drug (27% in 90 min) because of the decrease in particle size. Moreover, stability studies indicated that the crafted nanoformulation was stable at cold (4℃) as well as normal room temperature (25℃) for six months. From the obtained results, it was concluded that the combination of top-down and bottom- up approaches employed for the fabrication of oral nanosuspension is a remunerative and lucrative approach to successfully resolve the perplexities associated with the dissolution rate of poorly aqueous soluble BCS class-IV drug moieties such as chlorthalidone.
Abstract: Background: In a research facility, 7-azaindole derivatives were designed and synthesized, and each substance was examined for its capacity to inhibit cancer growth. In the present study, the synthesized analogues were docked with PARP enzyme to find a suitable site for PARP inhibition. Materials and Methods: 1H nuclear magnetic resonance, 13C NMR, and mass spectrometry were used to characterize all synthesized analogues of 7-azindole. On the MCF-7 cell line for breast cancer, their anticancer activity was assessed. The proteins of PARP-1 inhibitors were docked against using the protein IDs 6NRF, 6NRG, 6NRH, 6NRI, 6NRJ, and 6NTU. For 7-azaindole derivatives, the two docked proteins 6NRH and 6NRF performed best. Results: The most active compound against MCF-7 cell lines has a GI50 of 15.56 μM, which is compound 4g. The compounds 4a, 4b, 4c, 4i, and 4h also exhibited good anticancer activity so these compounds have the prospective to be used as PARP inhibitors. According to additional molecular docking studies these compounds can bind to protein targets 6NRH well. These compounds offer promising potential as PARP inhibitors for the development of novel medications. Conclusion: The results of the study were favorable and gave direction for the synthesis of some novel potent 7-Azaindole compounds as a PARP inhibitors. Keywords: 7-azaindole, Synthesis, Docking, Anticancer activity, PARP inhibitor.
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