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1.
Glob Ment Health (Camb) ; 11: e50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690572

RESUMO

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.

2.
Chem Biodivers ; : e202400109, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640439

RESUMO

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 copper catalyzed azide-alkyne cycloaddition (CuAAC) has emerged as a prominent method for producing 1,2,3-triazole with excellent yields and exceptional regioselectivity. 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 catalysts in various chemical reactions. 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.

3.
J Drug Target ; : 1-19, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38512151

RESUMO

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.

4.
Stem Cell Rev Rep ; 20(4): 881-899, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38429620

RESUMO

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.


Assuntos
Pesquisa Biomédica , Animais , Humanos , Modelos Animais , Inteligência Artificial
5.
Artigo em Inglês | MEDLINE | ID: mdl-38288815

RESUMO

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.

6.
J Biomol Struct Dyn ; 42(1): 362-383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36995068

RESUMO

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.


Assuntos
Desenho de Fármacos , Ácidos Hidroxâmicos , Simulação de Acoplamento Molecular , Ligantes , Ácidos Hidroxâmicos/farmacologia , Reprodutibilidade dos Testes , Simulação de Dinâmica Molecular , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Relação Quantitativa Estrutura-Atividade
7.
Cancer Biother Radiopharm ; 39(1): 19-34, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37797218

RESUMO

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.


Assuntos
Drosophila melanogaster , Neoplasias , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Transdução de Sinais , Receptores Notch/genética , Receptores Notch/metabolismo , Oncogenes
8.
Ther Deliv ; 14(12): 745-761, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38018431

RESUMO

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.


Assuntos
Lipossomos , alfa-Tocoferol , alfa-Tocoferol/farmacologia , Gefitinibe , Linhagem Celular Tumoral , Polietilenoglicóis , Vitamina E , Succinatos , Tamanho da Partícula
9.
Assay Drug Dev Technol ; 21(8): 345-356, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38010987

RESUMO

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.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Lipossomos , alfa-Tocoferol/farmacologia , alfa-Tocoferol/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Doxorrubicina/farmacologia , Succinatos/uso terapêutico , Linhagem Celular , Linhagem Celular Tumoral
10.
BJPsych Open ; 9(6): e190, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37822220

RESUMO

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.

11.
Nanomedicine (Lond) ; 18(19): 1261-1279, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37721134

RESUMO

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.

12.
Mol Divers ; 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37733243

RESUMO

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.

13.
BMC Public Health ; 23(1): 1562, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37587403

RESUMO

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.


Assuntos
Pessoal Administrativo , Lacunas de Evidências , Humanos , Síria , Canadá , Alemanha
14.
J Drug Target ; 31(9): 889-907, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37539789

RESUMO

Triple-negative breast cancer (TNBC), a subtype of breast cancer that lacks expression of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), has clinical features including a high degree of invasiveness, an elevated risk of metastasis, tendency to relapse, and poor prognosis. It constitutes around 10-15% of all breast cancer, and having heredity of BRCA1 mutated breast cancer could be a reason for the occurrence of TNBC in women. Overexpression of cellular and molecular targets, i.e. CD44 receptor, EGFR receptor, Folate receptor, Transferrin receptor, VEGF receptor, and Androgen receptor, have emerged as promising targets for treating TNBC. Signalling pathways such as Notch signalling and PI3K/AKT/mTOR also play a significant role in carrying out and managing crucial pro-survival and pro-growth cellular processes that can be utilised for targeted therapy against triple-negative breast cancer. This review sheds light on various targeting strategies, including cellular and molecular targets, signalling pathways, poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors PARP, immunotherapy, ADCs have all found a place in the current TNBC therapeutic paradigm. The role of photothermal therapy (PTT) and photodynamic therapy (PDT) has also been explored briefly.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Transdução de Sinais , Imunoterapia
15.
Biochem Pharmacol ; 215: 115723, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536473

RESUMO

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.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Hiperglicemia , Humanos , Neuropatias Diabéticas/tratamento farmacológico , Qualidade de Vida , Hiperglicemia/complicações , Transdução de Sinais , Proteína Quinase C/metabolismo , Diabetes Mellitus/tratamento farmacológico
16.
Curr Med Chem ; 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37581524

RESUMO

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.

17.
Curr Drug Metab ; 24(6): 406-421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37519199

RESUMO

One of the key factors contributing to mortality and morbidity globally is infectious ailments. According to recent statistics from WHO, amplified antimicrobial resistance occurrence among bacteria signifies the utmost threat to global public health. Bacteria have developed various strategies to resist antimicrobials, including enzymatic inactivation of antibiotics, drug efflux, modifications of the antibiotic molecule or chemical alteration of the antibiotic, limited drug uptake, etc. Furthermore, the inefficiency of antimicrobial drugs against resistant bacteria due to low solubility, instability, and associated side effects augments challenges to combat these resistant pathogens. This has attracted the attention of researchers to create nano-delivery and targeting techniques. This review presents an overview of antimicrobial resistance (AMR), its various subtypes, as well as mechanisms involved in AMR. This review also describes current strategies and applications of various nanocarriers, including nanoparticles, liposomes, lipid-based nanoparticles, micelles, and polymeric nanoparticles.

18.
BMJ Open ; 13(7): e064851, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474187

RESUMO

OBJECTIVES: To provide an overview of the holistic impact of the armed conflict on medical education and health professionals' training (MEHPT) in Syria. SETTING: Syria is a country which underwent an armed conflict for 10 years and suffered from the weaponisation of health. METHODS: A mixed-methods systematic review including quantitative, qualitative, mixed-methods and textual literature between 2011 and 2021 including papers on the Syrian MEHPT undergraduate and postgraduate education and training personnel (including medicine, dentistry, pharmacy, nursing, midwifery and allied health professionals). The electronic search was conducted in October 2018 in Embase, Global Health, Medline, PsycINFO, Web of Science, PubMed, Scopus, CINAHL and grey literature. And an update to the search was conducted in August 2021 in PubMed, Google Scholar and Trip database. OUTCOMES: The impact of conflict on the MEHPT system, personnel, experiences, challenges and channels of support. RESULTS: Of the 5710 citations screened, 70 met the inclusion criteria (34 quantitative, 3 qualitative, 1 mixed-method, and 32 reports and opinion papers). The two major cross-cutting themes were attacks on MEHPT and innovations (present in 41% and 44% of the papers, respectively), followed by challenges facing the MEHPT sector and attitudes and knowledge of trainees and students, and lastly health system and policy issues, and narrating experiences. CONCLUSION: Conflict in Syria has politicised all aspects of MEHPT. Influenced by political control, the MEHPT system has been divided into two distinguished geopolitical contexts; government-controlled areas (GCAs) and non-GCAs (NGCAs), each having its characteristics and level of war impact. International and regional academic institutes collaboration and coordination efforts are needed to formulate educational platforms using innovative approaches (such as online/blended/store-and-forward/peer-training/online tutoring) to strengthen and build the capacity of the health workforce in conflict-affected areas.


Assuntos
Educação Médica , Pessoal de Saúde , Humanos , Síria , Pessoal de Saúde/educação , Pessoal Técnico de Saúde , Conflitos Armados
19.
Confl Health ; 17(1): 29, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316903

RESUMO

BACKGROUND: Healthcare is a basic human right extending across all humanitarian contexts, including conflict. Globally, two billion people are living under conditions of insecurity and violent armed conflict with a consequent impact on public health. Health research in conflict-affected regions has been recognised as important to gain more understanding of the actual needs of such populations, to optimise healthcare delivery, as well as to inform advocacy and policy change. International collaborative research maximises the resources and skills available for dealing with global health issues, builds capacity and endeavours to ensure the research reflects real needs of the populations. Under the UK's Global Challenge Research Fund in 2017 a number of such international programs were created including the Research for Health in Conflict-Middle East and North Africa (R4HC-MENA) partnership to build capacity in conflict and health research as well as study specific areas, namely noncommunicable diseases in conflict (cancer & mental health) and the political economy of health in conflict. METHODS: A qualitative study using semi-structured online interviews was conducted to explore researchers' and stakeholders' perspectives on the R4HC-MENA programme over its lifetime from 2017 to 2021. It aimed to understand the factors that influenced and accelerated international collaboration within the R4HC-MENA programme on conflict and health research, and to provide deeper insights into the implementation of the programme. Data collection was conducted from March 2022 to June 2022. Purposive and snowball sampling techniques were used for participant recruitment. Thematic analysis was applied for data analysis. RESULTS: Twelve researchers/stakeholders participated in this study: four men and eight women. Four main themes were generated: Theme 1: Network building (personal and institutional levels); Theme 2: Hierarchies and power dynamics (power imbalance between different academic status, genders and institutions); Theme 3: Communication challenges; Theme 4: Career development (management, leadership, research, and teaching skills). CONCLUSIONS: This study provided preliminary insights into perspectives on international collaboration in a major international programme of research on conflict and health. Several key challenges and outputs were generated by the researchers in this study. The findings are important for further developing effective strategies to tackle the challenge of power imbalance and ineffective communication in international research collaborations.

20.
Environ Sci Pollut Res Int ; 30(27): 69727-69750, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37160511

RESUMO

Adsorption and photocatalytic properties of carbonaceous materials, viz., carbon nanotubes (CNTs), fullerene, graphene, graphene oxide, carbon nanofiber nanospheres, and activated carbon, are the legitimate weapons for the remediation of emerging and persistent inorganic/organic contaminants, heavy metals, and radionucleotides from the environment. High surface area, low or non-toxic nature, ease of synthesis, regeneration, and chemical modification of carbonaceous material make them ideal for the removal of toxicants. The research techniques investigated during the last decade for the elimination of environmental toxicants using carbonaceous materials are reviewed to offer comprehensive insight into the mechanism, efficiency, applications, advantages, and shortcomings. Opportunities and challenges associated with carbon materials have been discussed to suggest future perspectives in the remediation of environmental toxicants.


Assuntos
Recuperação e Remediação Ambiental , Nanotubos de Carbono , Poluentes Químicos da Água , Nanotubos de Carbono/química , Substâncias Perigosas , Carvão Vegetal , Adsorção , Poluentes Químicos da Água/química
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