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1.
Chirality ; 36(7): e23698, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38961803

ABSTRACT

Chirality, the property of molecules having mirror-image forms, plays a crucial role in pharmaceutical and biomedical research. This review highlights its growing importance, emphasizing how chiral drugs and nanomaterials impact drug effectiveness, safety, and diagnostics. Chiral molecules serve as precise diagnostic tools, aiding in accurate disease detection through unique biomolecule interactions. The article extensively covers chiral drug applications in treating cardiovascular diseases, CNS disorders, local anesthesia, anti-inflammatories, antimicrobials, and anticancer drugs. Additionally, it explores the emerging field of chiral nanomaterials, highlighting their suitability for biomedical applications in diagnostics and therapeutics, enhancing medical treatments.


Subject(s)
Nanostructures , Nanostructures/chemistry , Humans , Stereoisomerism , Pharmaceutical Preparations/chemistry , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology
2.
Global Health ; 20(1): 45, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845021

ABSTRACT

BACKGROUND: In conflict settings, as it is the case in Syria, it is crucial to enhance health information management to facilitate an effective and sustainable approach to strengthening health systems in such contexts. In this study, we aim to provide a baseline understanding of the present state of health information management in Northwest Syria (NWS) to better plan for strengthening the health information system of the area that is transitioning to an early-recovery stage. METHODS: A combination of questionnaires and subsequent interviews was used for data collection. Purposive sampling was used to select twenty-one respondents directly involved in managing and directing different domains of health information in the NWS who worked with local NGOs, INGOs, UN-agencies, or part of the Health Working Group. A scoring system for each public health domain was constructed based on the number and quality of the available datasets for these domains, which were established by Checci and others. RESULTS & CONCLUSIONS: Reliable and aggregate health information in the NWS is limited, despite some improvements made over the past decade. The conflict restricted and challenged efforts to establish a concentrated and harmonized HIS in the NWS, which led to a lack of leadership, poor coordination, and duplication of key activities. Although the UN established the EWARN and HeRAMS as common data collection systems in the NWS, they are directed toward advocacy and managed by external experts with little participation or access from local stakeholders to these datasets. RECOMMENDATIONS: There is a need for participatory approaches and the empowerment of local actors and local NGOs, cooperation between local and international stakeholders to increase access to data, and a central domain for planning, organization, and harmonizing the process. To enhance the humanitarian health response in Syria and other crisis areas, it is imperative to invest in data collection and utilisation, mHealth and eHealth technologies, capacity building, and robust technical and autonomous leadership.


Subject(s)
Health Information Management , Syria , Humans , Surveys and Questionnaires , Armed Conflicts
3.
Exp Eye Res ; 245: 109983, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38942133

ABSTRACT

Over the past twenty years, ocular gene therapy has primarily focused on addressing diseases linked to various genetic factors. The eye is an ideal candidate for gene therapy due to its unique characteristics, such as easy accessibility and the ability to target both corneal and retinal conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), age-related macular degeneration (AMD), and Stargardt disease. Currently, literature documents 33 clinical trials in this field, with the most promising results emerging from trials focused on LCA. These successes have catalyzed further research into other ocular conditions such as glaucoma, AMD, RP, and choroideremia. The effectiveness of gene therapy relies on the efficient delivery of genetic material to specific cells, ensuring sustained and optimal gene expression over time. Viral vectors have been widely used for this purpose, although concerns about potential risks such as immune reactions and genetic mutations have led to the development of non-viral vector systems. Preliminary laboratory research and clinical investigations have shown a connection between vector dosage and the intensity of immune response and inflammation in the eye. The method of administration significantly influences these reactions, with subretinal delivery resulting in a milder humoral response compared to the intravitreal route. This review discusses various ophthalmic diseases, including both corneal and retinal conditions, and their underlying mechanisms, highlighting recent advances and applications in ocular gene therapies.


Subject(s)
Genetic Therapy , Genetic Vectors , Humans , Genetic Therapy/methods , Eye Diseases/therapy , Eye Diseases/genetics , Gene Transfer Techniques , Retinal Diseases/therapy , Retinal Diseases/genetics , Animals
4.
Trends Plant Sci ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38902122

ABSTRACT

Cell-penetrating peptides (CPPs) are short (typically 5-30 amino acids), cationic, amphipathic, or hydrophobic peptides that facilitate the cellular uptake of diverse cargo molecules by eukaryotic cells via direct translocation or endocytosis across the plasma membrane. CPPs can deliver a variety of bioactive cargos, including proteins, peptides, nucleic acids, and small molecules into the cell. Once inside, the delivered cargo may function in the cytosol, nucleus, or other subcellular compartments. Numerous CPPs have been used for studies and drug delivery in mammalian systems. Although CPPs have many potential uses in plant research and agriculture, the application of CPPs in plants remains limited. Here we review the structures and mechanisms of CPPs and highlight their potential applications for sustainable agriculture.

5.
Article in English | MEDLINE | ID: mdl-38884850

ABSTRACT

Doxorubicin is a key treatment for breast cancer, but its effectiveness often comes with significant side effects. Its actions include DNA intercalation, topoisomerase II inhibition, and reactive oxygen species generation, leading to DNA damage and cell death. However, it can also cause heart problems and low blood cell counts. Current trials aim to improve doxorubicin therapy by adjusting doses, using different administration methods, and combining it with targeted treatments or immunotherapy. Nanoformulations show promise in enhancing doxorubicin's effectiveness by improving drug delivery, reducing side effects, and overcoming drug resistance. This review summarizes recent progress and difficulties in using doxorubicin for breast cancer, highlighting its mechanisms, side effects, ongoing trials, and the potential impact of nanoformulations. Understanding these different aspects is crucial in optimizing doxorubicin's use and improving outcomes for breast cancer patients. This review examines the toxicity of doxorubicin, a drug used in breast cancer treatment, and discusses strategies to mitigate adverse effects, such as cardioprotective agents and liposomal formulations. It also discusses clinical trials evaluating doxorubicin-based regimens, the evolving landscape of combination therapies, and the potential of nanoformulations to optimize delivery and reduce systemic toxicity. The review also discusses the potential of liposomes, nanoparticles, and polymeric micelles to enhance drug accumulation within tumor tissues while sparing healthy organs.

6.
Glob Ment Health (Camb) ; 11: e50, 2024.
Article in English | MEDLINE | ID: mdl-38690572

ABSTRACT

Since the beginning of the Syrian conflict in 2011, Syrians have faced violence and displacement causing an increase in mental health issues. The COVID-19 pandemic, the 2023 earthquake, and deteriorating living conditions have exacerbated these issues. Suicide in Syria remains an under-researched topic since accurate data are difficult to obtain. In this study, we aimed to explore the demographics and risk factors of suicide in Syria by performing a retrospective content analysis of selected online news (media) outlets from across Syria. Twelve news outlets from the three regions of Syria were selected and news of suicide cases were searched retrospectively. The age range was between 9 and 79 years old with the average age being 27.1 ± SD 5.9 years. The most reported causes of suicide were harsh living conditions (18.5%) and relationship problems (18.3%). The most common method of suicide was hanging followed by using firearms. More suicides occurred at night and in the summer and spring seasons. Based on our study's results, young adult, male, unmarried, individuals in rural settings and northern governorates were at the highest risk of suicide in Syria. This study highlights the urgent need for mental health interventions that address the unique challenges faced by Syrians.

7.
Chem Biodivers ; 21(6): e202400109, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38640439

ABSTRACT

The Huisgen cycloaddition, often referred to as 1,3-Dipolar cycloaddition, is a well-established method for synthesizing 1,4-disubstituted triazoles. Originally conducted under thermal conditions [3+2] cycloaddition reactions were limited by temperature, prolonged reaction time, and regioselectivity. The introduction of copper catalyzed azide-alkyne cycloaddition (CuAAC) revitalized interest, giving rise to the concept of "click chemistry". The CuAAC has emerged as a prominent method for producing 1,2,3-triazole with excellent yields and exceptional regioselectivity even in unfavorable conditions. Copper catalysts conventionally facilitate azide-alkyne cycloadditions, but challenges include instability and recycling issues. In recent years, there has been a growing demand for heterogeneous and porous catalysts in various chemical reactions. Chemists have been more interested in heterogenous catalysts as a result of the difficulties in separating homogenous catalysts from reaction products. These catalysts are favored for their abundant active sites, extensive surface area, easy separation from reaction mixtures, and the ability to be reused. Heterogeneous catalysts have garnered significant attention due to their broad industrial utility, characterized by cost-effectiveness, stability, resistance to thermal degradation, and ease of removal compared to their homogeneous counterparts. The present review covers recent advancements from year 2018 to 2023 in the field of click reactions for obtaining 1,2,3-triazoles through Cu catalyzed 1,3-dipolar azide-alkyne cycloaddition and the properties of the catalyst, reaction conditions such as solvent, temperature, reaction time, and the impact of different heterogeneous copper catalysts on product yield.


Subject(s)
Alkynes , Azides , Copper , Cycloaddition Reaction , Triazoles , Copper/chemistry , Triazoles/chemistry , Triazoles/chemical synthesis , Azides/chemistry , Alkynes/chemistry , Catalysis , Molecular Structure , Click Chemistry
8.
Stem Cell Rev Rep ; 20(4): 881-899, 2024 May.
Article in English | MEDLINE | ID: mdl-38429620

ABSTRACT

Biomedical research has long relied on animal models to unravel the intricacies of human physiology and pathology. However, concerns surrounding ethics, expenses, and inherent species differences have catalyzed the exploration of alternative avenues. The contemporary alternatives to traditional animal models in biomedical research delve into three main categories of alternative approaches: in vitro models, in vertebrate models, and in silico models. This unique approach to artificial intelligence and machine learning has been a keen interest to be used in different biomedical research. The main goal of this review is to serve as a guide to researchers seeking novel avenues for their investigations and underscores the importance of considering alternative models in the pursuit of scientific knowledge and medical breakthroughs, including showcasing the broad spectrum of modern approaches that are revolutionizing biomedical research and leading the way toward a more ethical, efficient, and innovative future. Models can insight into cellular processes, developmental biology, drug interaction, assessing toxicology, and understanding molecular mechanisms.


Subject(s)
Biomedical Research , Animals , Humans , Models, Animal , Artificial Intelligence
9.
J Drug Target ; 32(5): 510-528, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38512151

ABSTRACT

Aptamers, a novel type of targeted ligand used in drug delivery, have quickly gained popularity due to their high target specificity and affinity. Different aptamer-mediated drug delivery systems, such as aptamer-drug conjugate (ApDC), aptamer-siRNA, and aptamer-functionalised nanoparticle systems, are currently being developed for the successful treatment of cancer based on the excellent properties of aptamers. These systems can decrease potential toxicity and enhance therapeutic efficacy by targeting the drug moiety. In this review, we provide an overview of recent developments in aptamer-mediated delivery systems for cancer therapy, specifically for breast cancer, and talk about the potential applications and current issues of novel aptamer-based techniques. This study in aptamer technology for breast cancer therapy highlights key aptamers targeting well-established biomarkers such as HER2, oestrogen receptor, and progesterone receptor. Additionally, we explore the potential of aptamers in overcoming various challenges such as drug resistance and improving the delivery of therapeutic agents. This review aims to provide a deeper understanding of the present aptamer-based targeted delivery applications through in-depth analysis to increase efficacy and create new therapeutic approaches that may ultimately lead to better treatment outcomes for cancer patients.


Subject(s)
Antineoplastic Agents , Aptamers, Nucleotide , Breast Neoplasms , Drug Delivery Systems , Humans , Breast Neoplasms/drug therapy , Aptamers, Nucleotide/administration & dosage , Female , Drug Delivery Systems/methods , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Animals , Drug Resistance, Neoplasm
10.
Anticancer Agents Med Chem ; 24(8): 590-626, 2024.
Article in English | MEDLINE | ID: mdl-38288815

ABSTRACT

New drugs being established in the market every year produce specified structures for selective biological targeting. With medicinal insights into molecular recognition, these begot molecules open new rooms for designing potential new drug molecules. In this review, we report the compilation and analysis of a total of 56 drugs including 33 organic small molecules (Mobocertinib, Infigratinib, Sotorasib, Trilaciclib, Umbralisib, Tepotinib, Relugolix, Pralsetinib, Decitabine, Ripretinib, Selpercatinib, Capmatinib, Pemigatinib, Tucatinib, Selumetinib, Tazemetostat, Avapritinib, Zanubrutinib, Entrectinib, Pexidartinib, Darolutamide, Selinexor, Alpelisib, Erdafitinib, Gilteritinib, Larotrectinib, Glasdegib, Lorlatinib, Talazoparib, Dacomitinib, Duvelisib, Ivosidenib, Apalutamide), 6 metal complexes (Edotreotide Gallium Ga-68, fluoroestradiol F-18, Cu 64 dotatate, Gallium 68 PSMA-11, Piflufolastat F-18, 177Lu (lutetium)), 16 macromolecules as monoclonal antibody conjugates (Brentuximabvedotin, Amivantamab-vmjw, Loncastuximabtesirine, Dostarlimab, Margetuximab, Naxitamab, Belantamabmafodotin, Tafasitamab, Inebilizumab, SacituzumabGovitecan, Isatuximab, Trastuzumab, Enfortumabvedotin, Polatuzumab, Cemiplimab, Mogamulizumab) and 1 peptide enzyme (Erwiniachrysanthemi-derived asparaginase) approved by the U.S. FDA between 2018 to 2021. These drugs act as anticancer agents against various cancer types, especially non-small cell lung, lymphoma, breast, prostate, multiple myeloma, neuroendocrine tumor, cervical, bladder, cholangiocarcinoma, myeloid leukemia, gastrointestinal, neuroblastoma, thyroid, epithelioid and cutaneous squamous cell carcinoma. The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.


Subject(s)
Antineoplastic Agents , United States Food and Drug Administration , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , United States , Drug Approval , Neoplasms/drug therapy , Molecular Structure
11.
J Biomol Struct Dyn ; 42(1): 362-383, 2024.
Article in English | MEDLINE | ID: mdl-36995068

ABSTRACT

Histone deacetylases (HDACs) are critical epigenetic drug targets that have gained significant attention in the scientific community for the treatment of cancer. The currently marketed HDAC inhibitors lack selectivity for the various HDAC isoenzymes. Here, we describe our protocol for the discovery of novel potential hydroxamic acid based HDAC3 inhibitors through pharmacophore modeling, virtual screening, docking, molecular dynamics (MD) simulation and toxicity studies. The ten pharmacophore hypotheses were established, and their reliability was validated by different ROC (receiving operator curve) analysis. Among them, the best model (Hypothesis 9 or RRRA) was employed for searching SCHEMBL, ZINC and MolPort database to screen out hit molecules as selective HDAC3 inhibitors, followed by different docking stages. MD simulation (50 ns) and MMGBSA study were performed to study the stability of ligand binding modes and with the help of trajectory analysis, to calculate the ligand-receptor complex RMSD (root-mean-square deviation), RMSF (root-mean-square fluctuation) and H-bond distance, etc. Finally, in-silico toxicity studies were performed on top screened molecules and compared with reference drug SAHA and established structure-activity relationship (SAR). The results indicated that compound 31, with high inhibitory potency and less toxicity (probability value 0.418), is suitable for further experimental analysis.Communicated by Ramaswamy H. Sarma.


Pharmacophore modeling and virtual screening were performed with hydroxamic acid derivatives as HDAC3 inhibitors.MD simulation was performed for 50 ns time duration for selected protein-ligand complexes.SAR and toxicity studies (using TOPKAT tool) were performed.The results of these studies might be valuable in the further design and development of more potent HDAC3 inhibitors.


Subject(s)
Drug Design , Hydroxamic Acids , Molecular Docking Simulation , Ligands , Hydroxamic Acids/pharmacology , Reproducibility of Results , Molecular Dynamics Simulation , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Quantitative Structure-Activity Relationship
12.
Cancer Biother Radiopharm ; 39(1): 19-34, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37797218

ABSTRACT

It is now well understood that many signaling pathways are vital in carrying out and controlling essential pro-survival and pro-growth cellular functions. The NOTCH signaling pathway, a highly conserved evolutionary signaling pathway, has been thoroughly studied since the discovery of NOTCH phenotypes about 100 years ago in Drosophila melanogaster. Abnormal NOTCH signaling has been linked to the pathophysiology of several diseases, notably cancer. In tumorigenesis, NOTCH plays the role of a "double-edged sword," that is, it may act as an oncogene or as a tumor suppressor gene depending on the nature of the context. However, its involvement in several cancers and inhibition of the same provides targeted therapy for the management of cancer. The use of gamma (γ)-secretase inhibitors and monoclonal antibodies for cancer treatment involved NOTCH receptors inhibition, leading to the possibility of a targeted approach for cancer treatment. Likewise, several natural compounds, including curcumin, resveratrol, diallyl sulfide, and genistein, also play a dynamic role in the management of cancer by inhibition of NOTCH receptors. This review outlines the functions and structure of NOTCH receptors and their associated ligands with the mechanism of the signaling pathway. In addition, it also emphasizes the role of NOTCH-targeted nanomedicine in various cancer treatment strategies.


Subject(s)
Drosophila melanogaster , Neoplasms , Animals , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Signal Transduction , Receptors, Notch/genetics , Receptors, Notch/metabolism , Oncogenes
13.
Assay Drug Dev Technol ; 21(8): 345-356, 2023.
Article in English | MEDLINE | ID: mdl-38010987

ABSTRACT

Present research work reports the development of doxorubicin (DOX) loaded α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes. The developed formulation was evaluated for its anticancer potential and intracellular uptake against the MDA-MB-231 breast cancer cell line. Moreover, hemocompatibility studies were also done on human blood red blood cells for the determination of blood compatibility. The prepared doxorubicin-loaded TPGS liposomes (DOX-LIPO-TPGS) and doxorubicin-loaded cationic liposomes (DOX-LIPO+-TPGS) reveal vesicle size (177.5 ± 2.5 and 201.7 ± 2.3 nm), polydispersity index (0.189 ± 0.01 and 0.218 ± 0.02), zeta potential (-36.9 ± 0.7 and 42 ± 0.9 mv), and % entrapment efficiency (65.88% ± 3.7% and 74.5% ± 3.9%). Furthermore, in vitro, drug release kinetics of the drug alone and drug from formulation shows sustained release behavior of developed formulation with 99.98% in 12 h and 80.98% release of the drug in 72 h, respectively. In addition, cytotoxicity studies and cellular DOX uptake on the MDA-MB-231 breast cancer cell line depict higher cytotoxic and drug uptake potential with better hemocompatibility of DOX-LIPO+-TPGS with respect to DOX. The data from the study revealed that TPGS plays an important role in enhancing the formulation's quality attributes like stability, drug release, cytotoxicity, and hemocompatibility behavior. This may serve that TPGS-coated cationic liposome as a vital candidate for the treatment of cancer and drug delivery in case of breast cancer.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Liposomes , alpha-Tocopherol/pharmacology , alpha-Tocopherol/therapeutic use , Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/drug therapy , Doxorubicin/pharmacology , Succinates/therapeutic use , Cell Line , Cell Line, Tumor
14.
Ther Deliv ; 14(12): 745-761, 2023 12.
Article in English | MEDLINE | ID: mdl-38018431

ABSTRACT

Aim: Gefitinib-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes (GEF-TPGS-LIPO+) were developed and optimized by the quality by design (QbD) approach for its potential anticancer effect. Methods/materials: Box-Behnken design (BBD) a systematic design of experiments was added to screen and optimize the formulation variables. Results: GEF-TPGS-LIPO+ shows vesicle size (210 ± 4.82 nm), polydispersity index (0.271 ± 0.002), zeta potential (22.2 ± 0.84 mV) and entrapment efficiency (82.3 ± 1.95). MTT result shows the enhanced cytotoxicity and higher intracellular drug uptake with highest and lowest levels of the reactive oxygen species and NF-κB expressions on A549 lung cancer cells, determined by fluorescence-activated cell sorting flow cytometry. Conclusion: Potential anticancer effect on A549 cells might be found due to cationic liposomal interaction with cancer cells.


Subject(s)
Liposomes , alpha-Tocopherol , alpha-Tocopherol/pharmacology , Gefitinib , Cell Line, Tumor , Polyethylene Glycols , Vitamin E , Succinates , Particle Size
15.
BJPsych Open ; 9(6): e190, 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37822220

ABSTRACT

BACKGROUND: Despite theoretical support for including mental health and psychosocial support (MHPSS) with peacebuilding, few programmes in conflict-affected regions fully integrate these approaches. AIMS: To describe and assess preliminary outcomes of the Counselling on Wheels programme delivered by the NEEM Foundation in the Borno State of North-East Nigeria. METHOD: We first describe the components of the Counselling on Wheels programme, including education and advocacy for peace and social cohesion through community peacebuilding partnerships and activities, and an MHPSS intervention open to all adults, delivered in groups of eight to ten people. We then conducted secondary analysis of data from 1550 adults who took part in the MHPSS intervention, who provided data at baseline and 1-2 weeks after the final group session. Vulnerability to violent extremism was assessed with a locally developed 80-item scale. Symptoms of common mental disorders were assessed with the Depression, Anxiety and Stress Scale (DASS-21) and Post-Traumatic Stress Disorder Scale (PTSD-8). Data were analysed through a mixed-effect linear regression model, accounting for clustering by community and adjusted for age and gender. RESULTS: After taking part in group MHPSS, scores fell for depression (-5.8, 95% CI -6.7 to -5.0), stress (-5.5, 95% CI -6.3 to -4.6), post-traumatic stress disorder (-2.9, 95% CI -3.4 to -2.4) and vulnerability to violent extremism (-44.6, 95% CI -50.6 to -38.6). CONCLUSIONS: The Counselling on Wheels programme shows promise as a model for integrating MHPSS with community peacebuilding activities in this conflict-affected region of Africa.

16.
Mol Divers ; 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37733243

ABSTRACT

Diabetes Mellitus (DM) is the globe's common leading disease which is caused by high consumption of glucose. DM compiles groups of metabolic disorders which are characterized by inadequate secretion of insulin from pancreas, resulting in hyperglycemia condition. Many enzymes play a vital role in the metabolism of carbohydrate known as α-amylase and α-glucosidase which is calcium metalloenzyme that leads to breakdown of complex polysaccharides into glucose. To tackle this problem, search for newer antidiabetic drugs is the utmost need for the treatment and/or management of increasing diabetic burden. The inhibition of α-amylase and α-glucosidase is one of the effective therapeutic approaches for the development of antidiabetic therapeutics. The exhaustive literature survey has shown the importance of medicinally privileged triazole specifically 1,2,3-triazol and 1,2,4-triazoles scaffold tethered, fused and/or clubbed with other heterocyclic rings structures as promising agents for designing and development of novel antidiabetic therapeutics. Molecular hybrids namely pyridazine-triazole, pyrazoline-triazole, benzothiazole-triazole, benzimidazole-triazole, curcumin-triazole, (bis)coumarin-triazole, acridine-9-carboxamide linked triazole, quinazolinone-triazole, xanthone-triazole, thiazolo-triazole, thiosemicarbazide-triazole, and indole clubbed-triazole are few examples which have shown promising antidiabetic activity by inhibiting α-amylase and/or α-glucosidase. The present review summarizes the structure-activity relationship (SAR), enzyme inhibitory activity including IC50 values, percentage inhibition, kinetic studies, molecular docking studies, and patents filed of the both scaffolds as alpha-amylase and alpha-glucosidase inhibitors, which may be used for further development of potent inhibitors against both enzymes.

17.
Nanomedicine (Lond) ; 18(19): 1261-1279, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37721134

ABSTRACT

Aims: To develop an estrone-targeted d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based liposomal system for enhanced intracellular delivery of doxorubicin (DOX). Materials & methods: Zetasizer, transmission electron microscopy, energy dispersive x-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction, confocal laser scanning microscopy and FACS analysis were used for formulation characterization and evaluation. Results: The DOX-LIPO-TPGS and DOX-LIPO-TPGS-estrone formulations had vesicle sizes (117.6 ± 3.51; 144 ± 5.00 nm), zeta potential (-36.4 ± 0.75; -35.8 ± 0.76), polydispersity index (0.123 ± 0.005; 0.169 ± 0.005) and percent entrapment efficiency (73.56 ± 3.55; 77.16 ± 3.83%) with improved cytotoxicity and cellular uptake, confirming the targeted potential of the developed formulations. Conclusion: The results suggest that the developed liposomal formulation with desired characteristics is potentially capable of nonimmunogenic, site-specific drug delivery to targeted cancer sites and reduced DOX-associated cardiac toxicity.


Doxorubicin (DOX) is an effective chemotherapy drug to treat breast cancer. However, DOX can cause unwanted side effects such as damage to the heart. This is due to side effects in healthy body tissues. This study was designed to develop nanoparticles that target cancer cells specifically to improve the delivery of DOX to these cells and prevent side effects elsewhere. Nanoparticles called liposomes were used as the platform for delivering DOX. Liposomes are sometimes coated with d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS), a synthetic vitamin D derivative. This helps the liposome evade the immune system and release the drug more effectively. TPGS was tethered with estrone (ES), a type of estrogen. Certain breast cancer cells have many more estrogen receptors on their cell surface than healthy cells. TPGS-ES was coated on DOX-loaded liposomes to achieve enhanced intracellular delivery of DOX to breast cancer cells specifically. These liposomes were called DOX-LIPO-TPGS-ES. This liposome proved more toxic to cells in a breast cancer cell line than free DOX or liposomes without tethered ES. When tested in rats, DOX-LIPO-TPGS-ES showed increased tumor uptake compared with free DOX or liposomes without tethered ES. Rats treated with either liposomal drug showed normal levels of key markers associated with heart function, whereas those treated with free DOX showed increased levels of these markers. These results suggest that DOX-LIPO-TPGS-ES is capable of highly targeted delivery of DOX with limited side effects.

18.
BMC Public Health ; 23(1): 1562, 2023 08 17.
Article in English | MEDLINE | ID: mdl-37587403

ABSTRACT

BACKGROUND: Syria has been in continuous conflict since 2011, resulting in more than 874,000 deaths and 13.7 million internally displaced people (IDPs) and refugees. The health and humanitarian sectors have been severely affected by the protracted, complex conflict and have relied heavily on donor aid in the last decade. This study examines the extent and implications of health aid displacement in Syria during acute humanitarian health crises from 2011 to 2019. METHODS: We conducted a trend analysis on data related to humanitarian and health aid for Syria between 2011 and 2019 from the OECD's Creditor Reporting System. We linked the data obtained for health aid displacement to four key dimensions of the Syrian conflict. The data were compared with other fragile states. We conducted a workshop in Turkey and key informants with experts, policy makers and aid practitioners involved in the humanitarian and health response in Syria between August and October 2021 to corroborate the quantitative data obtained by analysing aid repository data. RESULTS: The findings suggest that there was health aid displacement in Syria during key periods of crisis by a few key donors, such as the EU, Germany, Norway and Canada supporting responses to certain humanitarian crises. However, considering that the value of humanitarian aid is 50 times that of health aid, this displacement cannot be considered as critical. Also, there was insufficient evidence of health displacement across all donors. The results also showed that the value of health aid as a proportion of aggregate health and humanitarian aid is only 2% in Syria, compared to 22% for the combined average of fragile states, which further indicates the predominance of humanitarian aid over health aid in the Syrian crisis context. CONCLUSION: This study highlights that in very complex conflict-affected contexts such as Syria, it is difficult to suggest the use of health aid displacement as an effective tool for aid-effectiveness for donors as it does not reflect domestic needs and priorities. Yet there seems to be evidence of slight displacement for individual donors. However, we can suggest that donors vastly prefer to focus their investment in the humanitarian sector rather than the health sector in conflict-affected areas. There is an urgent need to increase donors' focus on Syria's health development aid and adopt the humanitarian-development-peace nexus to improve aid effectiveness that aligns with the increasing health needs of local communities, including IDPs, in this protracted conflict.


Subject(s)
Administrative Personnel , Evidence Gaps , Humans , Syria , Canada , Germany
19.
Curr Med Chem ; 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37581524

ABSTRACT

Morbidity, disability, and healthcare expenses associated with rheumatoid arthritis (RA) impose a considerable health and economical burden on both patients and healthcare systems. This review aimed to examine the pathophysiological aspects of RA that may help design different types of drugs and drug delivery systems. These include monoclonal antibodies, immunoglobulins, tiny chemicals, and transgenes for gene therapy. These novel nanocarrier-based therapies target the underlying biological processes involved in RA while minimizing the systemic adverse effects of drugs.

20.
Biochem Pharmacol ; 215: 115723, 2023 09.
Article in English | MEDLINE | ID: mdl-37536473

ABSTRACT

Diabetic neuropathy is a neuro-degenerative disorder that encompasses numerous factors that impact peripheral nerves in the context of diabetes mellitus (DM). Diabetic peripheral neuropathy (DPN) is very prevalent and impacts 50% of diabetic patients. DPN is a length-dependent peripheral nerve lesion that primarily causes distal sensory loss, discomfort, and foot ulceration that may lead to amputation. The pathophysiology is yet to be fully understood, but current literature on the pathophysiology of DPN revolves around understanding various signaling cascades involving the polyol, hexosamine, protein-kinase C, AGE, oxidative stress, and poly (ADP ribose) polymerase pathways. The results of research have suggested that hyperglycemia target Schwann cells and in severe cases, demyelination resulting in central and peripheral sensitization is evident in diabetic patients. Various diagnostic approaches are available, but detection at an early stage remains a challenge. Traditional analgesics and opioids that can be used "as required" have not been the mainstay of treatment thus far. Instead, anticonvulsants and antidepressants that must be taken routinely over time have been the most common treatments. For now, prolonging life and preserving the quality of life are the ultimate goals of diabetes treatment. Furthermore, the rising prevalence of DPN has substantial consequences for occupational therapy because such therapy is necessary for supporting wellness, warding off other chronic-diseases, and avoiding the development of a disability; this is accomplished by engaging in fulfilling activities like yoga, meditation, and physical exercise. Therefore, occupational therapy, along with palliative therapy, may prove to be crucial in halting the onset of neuropathic-symptoms and in lessening those symptoms once they have occurred.


Subject(s)
Diabetes Mellitus , Diabetic Neuropathies , Hyperglycemia , Humans , Diabetic Neuropathies/drug therapy , Quality of Life , Hyperglycemia/complications , Signal Transduction , Protein Kinase C/metabolism , Diabetes Mellitus/drug therapy
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