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1.
Artigo em Inglês | MEDLINE | ID: mdl-38957977

RESUMO

Background: Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is substantially higher in cesarean section procedures. Approximately 8% of women who undergo cesarean sections are susceptible to infection. Although the body of evidence supporting the regular pre-operative utilization of prophylactic antibiotic treatment is steadily expanding, its usefulness in cesarean sections has not yet been standardized, and post-partum infection is still a serious medical challenge. We aimed to retrospectively assess the prophylactic effectiveness of cefazolin in combination with other antibiotic agents in cesarean sections. Materials and Methods: Both uni-variable and multi-variable analyses were conducted to identify factors that may affect cefazolin pre-operative antibiotic prophylaxis in elective cesarean section operations. The uni-variable analysis included timing of administration, operation duration, body mass index (BMI), and wound type. A multi-variable logistic regression model was then created to determine which variables provide independent information in the context of other variables. Results: Time of administration did not affect prophylactic cefazolin efficacy. However, prophylactic cefazolin was 1.43 and 1.77 times more effective when the operation lasted for 45 minutes or more, compared with operations that were shorter than 45 minutes. Patients with a BMI ranging from 18 to 29 kg/m2 showed increased efficacy of prophylactic cefazolin compared with obese patients with a BMI exceeding 30 kg/m2. The effectiveness of prophylactic cefazolin decreased by 95% in patients with clean-contaminated surgical incisions compared with those with clean surgical incisions. Conclusions: Our findings demonstrate that administering pre-operative prophylactic antibiotic agents to women undergoing cesarean section resulted in a reduction in post-partum infections, thereby reducing maternal mortality. Furthermore, optimal timing of administration, re-dosing if necessary, length of prophylactic medication, and dosing adjustments for obese patients are crucial factors in preventing surgical site infections and promoting antimicrobial stewardship.

2.
Sci Rep ; 14(1): 17426, 2024 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075176

RESUMO

Rhinoviruses (RVs) cause upper respiratory tract infections and pneumonia in children and adults. These non-enveloped viruses contain viral coats of four capsid proteins: VP1, VP2, VP3, and VP4. The canyon on VP1 used cell surface receptor ICAM-1 as the site of attachment and for the internalization of viruses. To date, there has been no drug or vaccine available against RVs. In this study, bioactive natural compounds of rosemary (Salvia rosmarinus L.), which are known for their pharmacological potential, were considered to target the VP1 protein. A total of 30 bioactive natural compounds of rosemary were taken as ligands to target viral proteins. The PkCSM tool was used to detect their adherence to Lipinski's rule of five and the ADMET properties of the selected ligands. Further, the CB-Dock tool was used for molecular docking studies between the VP1 protein and ligands. Based on the molecular docking and ADMET profiling results, phenethyl amine (4 methoxy benzyl) was selected as the lead compound. A comparative study was performed between the lead compound and two antiviral drugs, Placonaril and Nitazoxanide, to investigate the higher potential of natural compounds over synthetic drugs. Placonaril also targets VP1 but failed in clinical trials while Nitazoxanide was examined in clinical trials against rhinoviruses. It was discovered from this study that the (4 methoxy benzyl) phenethyl amine exhibited less toxicity in comparison to other tested drugs against RVs. More research is needed to determine its potential and make it a good medication against RVs.


Assuntos
Antivirais , Simulação de Acoplamento Molecular , Óleos Voláteis , Extratos Vegetais , Rhinovirus , Antivirais/farmacologia , Antivirais/química , Rhinovirus/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Rosmarinus/química , Simulação por Computador , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/química , Ligantes
3.
Front Pharmacol ; 15: 1406653, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835668

RESUMO

Background: P. aeruginosa, a significant bacterium, can cause severe illness and resistance to antibiotics. Quorum sensing (QS) systems regulate virulence factors production. Targeting QS could reduce bacteria pathogenicity and prevent antibiotic resistance. Cruciferous vegetables contain sulforaphane, known for its anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Aim: We aimed to examine the inhibitory influences of sulforaphane, at a sub-inhibitory concentration (» minimum inhibitory concentration, MIC), on virulence and QS in P. aeruginosa. Materials and methods: The sulforaphane's anti-virulence actions at sub-inhibitory concentrations were explored in vitro and in vivo. A sub-MIC concentration of sulforaphane was combined with anti-pseudomonal drugs, and the results of this combination were assessed. The virtual affinity of sulforaphane for the receptors of QS was studied, and its effect on the expression of QS genes was quantified. Results: Sulforaphane significantly decreased the biofilm formation, motility, ability to withstand oxidative stress, and the synthesis of virulence extracellular enzymes such as proteases, hemolysins, and elastase, as well as other virulence factors like pyocyanin. In addition, sulforaphane lessened the severity of P. aeruginosa infection in mice. Sulforaphane reduced the antipseudomonal antibiotics' MICs when used together, resulting in synergistic effects. The observed anti-virulence impacts were attributed to the ability of sulforaphane to inhibit QS via suppressing the QS genes' expression. Conclusion: Sulforaphane shows promise as a potent anti-virulence and anti-QS agent that can be used alongside conventional antimicrobials to manage severe infections effectively. Furthermore, this study paves the way for further investigation of sulforaphane and similar structures as pharmacophores for anti-QS candidates.

4.
Crit Rev Microbiol ; : 1-25, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556797

RESUMO

Available evidence illustrates that microbiome is a promising target for the study of growth, diagnosis and therapy of various types of cancer. Lung cancer is a leading cause of cancer death worldwide. The relationship of microbiota and their products with diverse pathologic conditions has been getting large attention. The novel research suggests that the microbiome plays an important role in the growth and progression of lung cancer. The lung microbiome plays a crucial role in maintaining mucosal immunity and synchronizing the stability between tolerance and inflammation. Alteration in microbiome is identified as a critical player in the progression of lung cancer and negatively impacts the patient. Studies suggest that healthy microbiome is essential for effective therapy. Various clinical trials and research are focusing on enhancing the treatment efficacy by altering the microbiome. The regulation of microbiota will provide innovative and promising treatment strategies for the maintenance of host homeostasis and the prevention of lung cancer in lung cancer patients. In the current review article, we presented the latest progress about the involvement of microbiome in the growth and diagnosis of lung cancer. Furthermore, we also assessed the therapeutic status of the microbiome for the management and treatment of lung cancer.

5.
Mol Divers ; 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678137

RESUMO

Suppressing vascular endothelial growth factor (VEGF), its receptor (VEGFR2), and the VEGF/VEGFR2 signaling cascade system to inhibit angiogenesis has emerged as a possible cancer therapeutic target. The present work was designed to discover and evaluate bioactive phytochemicals from the Clerodendrum inerme (L.) Gaertn plant for their anti-angiogenic potential. Molecular docking of twenty-one phytochemicals against the VEGFR-2 (PDB ID: 3VHE) protein was performed, followed by ADMET profiling and molecular docking simulations. These investigations unveiled two hit compounds, cirsimaritin (- 12.29 kcal/mol) and salvigenin (- 12.14 kcal/mol), with the highest binding energy values when compared to the reference drug, Sorafenib (- 15.14 kcal/mol). Furthermore, only nine phytochemicals (cirsimaritin and salvigenin included) obeyed Lipinski's rule of five and passed ADMET filters. Molecular dynamics simulations run over 100 ns revealed that the protein-ligand complexes remained stable with minimal backbone fluctuations. The binding free energy values of cirsimaritin (- 52.35 kcal/mol) and salvigenin (- 55.89 kcal/mol), deciphered by MM-GBSA analyses, further corroborated the docking interactions. The HOMO-LUMO band energy gap (ΔE) was calculated using density-functional theory (DFT) and substantiated using density of state (DOS) spectra. The chemical reactivity analyses revealed that salvigenin exhibited the highest chemical softness value (6.384 eV), the lowest hardness value (0.07831 eV), and the lowest ΔE value (0.1566 eV), which implies salvigenin was less stable and chemically more reactive than cirsimaritin and sorafenib. These findings provide further evidence that cirsimaritin and salvigenin have the ability to prevent angiogenesis and the development of cancer. Nevertheless, more in vitro and in vivo confirmation is necessary.

6.
Ageing Res Rev ; 96: 102276, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38499161

RESUMO

Amyloidosis of protein caused by fibrillation and aggregation are some of the most exciting new edges not only in protein sciences but also in molecular medicines. The present review discusses recent advancements in the field of neurodegenerative diseases and therapeutic applications with ongoing clinical trials, featuring new areas of protein misfolding resulting in aggregation. The endogenous accretion of protein fibrils having fibrillar morphology symbolizes the beginning of neuro-disorders. Prognostic amyloidosis is prominent in numerous degenerative infections such as Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis (ALS), etc. However, the molecular basis determining the intracellular or extracellular evidence of aggregates, playing a significant role as a causative factor in neurodegeneration is still unclear. Structural conversions and protein self-assembly resulting in the formation of amyloid oligomers and fibrils are important events in the pathophysiology of the disease. This comprehensive review sheds light on the evolving landscape of potential treatment modalities, highlighting the ongoing clinical trials and the potential socio-economic impact of novel therapeutic interventions in the realm of neurodegenerative diseases. Furthermore, many drugs are undergoing different levels of clinical trials that would certainly help in treating these disorders and will surely improve the socio-impact of human life.


Assuntos
Amiloidose , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Amiloide/metabolismo , Amiloidose/metabolismo , Doenças Neurodegenerativas/metabolismo , Doença de Parkinson/metabolismo , Proteínas Amiloidogênicas , Percepção
7.
RSC Adv ; 14(1): 160-180, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38173594

RESUMO

Objective: To enhance the brain bioavailability of S-allyl-l-cysteine (SC) by developing novel S-allyl-l-cysteine chitosan nanoparticles (SC CS NPs) and examining the quantity of SC by developing a novel method of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in ischemic rat brain treatment. Methods: The ionotropic gelation method was used to develop S-allyl cysteine-loaded CS NPs. The 4-factor, 5-level central composite design was optimized to determine the effect of independent variables, i.e., particle size, polydispersity index (PDI), zeta potential, EE, and loading capacity, together with their characterization, followed by drug release and intranasal permeation to enhance the brain bioavailability and examination of their neurobehavioral and biochemical parameters with their histopathological examination. Results: SC CS NPs were optimized at the particle size of 93.21 ± 3.31 nm (PDI: 0.317 ± 0.003), zeta potential of 44.4 ± 2.93, and drug loading of 41.23 ± 1.97% with an entrapment efficiency of 82.61 ± 4.93% having sustain and controlled release (79.92 ± 3.86%) with great permeation (>80.0%) of SC. SC showed the retention time of 1.021 min and 162.50/73.05 m/z. SC showed good linearity in the range of 5.0-1300.0 ng mL-1, % inter-and-intraday accuracy of 96.00-99.06% and CV of 4.38-4.38%. We observed significant results, i.e., p < 0.001 for improved (AUC)0-24 and Cmax delivered via i.v. and i.n. dose. We also observed the highly significantly observations of SC CS NPs (i.n.) based on their treatment results for the biochemical, neurobehavioral, and histopathological examination in the developed ischemic MCAO brain rat model. Conclusion: The excellent significant role of mucoadhesive CS NPs of SC was proven based on the enhancement in the brain bioavailability of SC via i.n. delivery in rats and easy targeting of the brain for ischemic brain treatment followed by an improvement in neuroprotection based on a very small dose of SC.

8.
Diagnostics (Basel) ; 13(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37761346

RESUMO

Intestinal parasitic infections pose a grave threat to human health, particularly in tropical and subtropical regions. The traditional manual microscopy system of intestinal parasite detection remains the gold standard procedure for diagnosing parasite cysts or eggs. This approach is costly, time-consuming (30 min per sample), highly tedious, and requires a specialist. However, computer vision, based on deep learning, has made great strides in recent years. Despite the significant advances in deep convolutional neural network-based architectures, little research has been conducted to explore these techniques' potential in parasitology, specifically for intestinal parasites. This research presents a novel proposal for state-of-the-art transfer learning architecture for the detection and classification of intestinal parasite eggs from images. The ultimate goal is to ensure prompt treatment for patients while also alleviating the burden on experts. Our approach comprised two main stages: image pre-processing and augmentation in the first stage, and YOLOv5 algorithms for detection and classification in the second stage, followed by performance comparison based on different parameters. Remarkably, our algorithms achieved a mean average precision of approximately 97% and a detection time of only 8.5 ms per sample for a dataset of 5393 intestinal parasite images. This innovative approach holds tremendous potential to form a solid theoretical basis for real-time detection and classification in routine clinical examinations, addressing the increasing demand and accelerating the diagnostic process. Our research contributes to the development of cutting-edge technologies for the efficient and accurate detection of intestinal parasite eggs, advancing the field of medical imaging and diagnosis.

9.
Pharmaceuticals (Basel) ; 16(7)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37513820

RESUMO

The neurodegenerative condition known as Parkinson's disease (PD) is brought on by the depletion of dopaminergic neurons in the basal ganglia, which is the brain region that controls body movement. PD occurs due to many factors, from which one of the acknowledged effects of oxidative stress is pathogenic pathways that play a role in the development of Parkinson's disease. Antioxidants, including flavonoids, vitamins E and C, and polyphenolic substances, help to reduce the oxidative stress brought on by free radicals. Consequently, this lowers the risk of neurodegenerative disorders in the long term. Although there is currently no cure for neurodegenerative illnesses, these conditions can be controlled. The treatment of this disease lessens its symptoms, which helps to preserve the patient's quality of life. Therefore, the use of naturally occurring antioxidants, such as polyphenols, which may be obtained through food or nutritional supplements and have a variety of positive effects, has emerged as an appealing alternative management strategy. This article will examine the extent of knowledge about antioxidants in the treatment of neurodegenerative illnesses, as well as future directions for research. Additionally, an evaluation of the value of antioxidants as neuroprotective agents will be provided.

10.
J Mater Chem B ; 11(25): 5668-5692, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37249518

RESUMO

Instinctive gastrointestinal inflammatory conditions with persistent intestinal inflammation are known as "inflammatory bowel diseases" (IBDs). IBDs are growing progressively common throughout the world although it is still unclear what causes them. IBDs that cause recurrent, intermittent, and disburse inflammatory responses, may also have systemic symptoms such as ulcerative colitis and Crohn's disease. It has been discovered that a number of medications, including antibiotics, corticosteroids, and immune-suppressants, can promote mucous and damaged epithelial restoration. The incidences of general and specific therapy failure in IBD continue to climb, even though the availability of advanced biologics including anti-interleukins, anti-integrins, anti-tumor necrosis factor (anti-TNF), and small molecules such as tofacitinib exist. Management therapies that are currently being researched include specifically JAK (janus kinase) inhibitors, anti-IL (anti-interleukin) (IL-12, IL23), and leukocyte inhibitors such as sphingosine-1-phosphate receptors. Clinical treatments can have various adverse effects. In order to give pharmacological drugs to the disease-specific sites with improved efficacy and fewer complications, innovative frameworks centered on biomaterials are needed. We provide an outlook on the current state of several biomaterials used to treat IBD. This article comprehensively addresses numerous microparticles, nanoparticles, and hydrogels that have recently been made from natural bio-polymers and lipids. To support colon-specific target delivery and steady release of medications during IBD therapies, these various biomaterial-based monotherapies could be employed as efficient drug delivery systems.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Intestinos , Imunomodulação
11.
J Cancer ; 14(3): 490-504, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860921

RESUMO

Cancer is the major challenge across world and the adenocarcinoma of prostate malignancy is the second most prevalent male cancer. Various medicinal plants are used for the treatment and management of various cancers. Matricaria chamomilla L., is one of the extensively used Unani medicament for the treatment of various type of diseases. In the current study we evaluated most of the parameters prescribed for drug standardization using pharmacognostic approaches. The 2,2 Diphenyl-1-picryl hydrazyl (DPPH) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. Moreover, we analyzed the antioxidant and cytotoxic activity of M. chamomilla (Gul-e Babuna) through in-vitro method. DPPH (2,2-diphenyl-1-picryl-hydrazl-hydrate) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. CFU and wound healing assay were performed to determine the anti-cancer activity. The results demonstrated that various extracts of M. chamomilla fulfilled most of the parameters of drug standardization and contained good antioxidant and anticancer activities. The ethyl acetate showed higher anticancer activity followed by aqueous, hydroalcoholic, petroleum benzene and methanol by CFU method. Also, the wound healing assay demonstrated that ethyl acetate extract has more significant effect followed by methanol and petroleum benzene extract on prostate cancer cell line (C4-2). The current study concluded that the extract of M. chamomilla flowers could act as good source of natural anti-cancer compounds.

12.
Front Mol Biosci ; 10: 1104577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825200

RESUMO

The most severe clinical manifestations of the horrifying COVID-19 disease, that claimed millions of lives during the pandemic time, were Acute respiratory distress syndrome (ARDS), Coagulopathies, septic shock leading eventually to death. ARDS was a consequence of Cytokine storm. The viral SARS-COV2infection lead to avalanche of cytokines and eicosanoids causing "cytokine storm" and "eicosanoid storm." Cytokine storm is one of the macrophage-derived inflammatory responses triggered by binding of virus particles to ACE2 receptors of alveolar macrophages, arise mainly due to over production of various pro-inflammatory mediators like cytokines, e.g., interleukin (IL)-1, IL-2, and tumor necrosis factor (TNF)- α, causing pulmonary edema, acute respiratory distress, and multi-organ failure. Cytokine storm was regarded as the predictor of severity of the disease and was deemed one of the causes of the high mortality rates due to the COVID-19. The basis of cytokine storm is imbalanced switching between an inflammation increasing - pro-inflammatory (M1) and an inflammation regulating-anti-inflammatory (M2) forms of alveolar macrophages which further deteriorates if opportunistic secondary bacterial infections prevail in the lungs. Lack of sufficient knowledge regarding the virus and its influence on co-morbidities, clinical treatment of the diseases included exorbitant use of antibiotics to mitigate secondary bacterial infections, which led to the unwarranted development of multidrug resistance (MDR) among the population across the globe. Antimicrobial resistance (AMR) needs to be addressed from various perspectives as it may deprive future generations of the basic health immunity. Specialized pro-resolving mediators (SPMs) are generated from the stereoselective enzymatic conversions of essential fatty acids that serve as immune resolvents in controlling acute inflammatory responses. SPMs facilitate the clearance of injured tissue and cell debris, the removal of pathogens, and augment the concentration of anti-inflammatory lipid mediators. The SPMs, e.g., lipoxins, protectins, and resolvins have been implicated in exerting inhibitory influence on with cytokine storm. Experimental evidence suggests that SPMS lower antibiotic requirement. Therefore, in this review potential roles of SPMs in enhancing macrophage polarization, triggering immunological functions, hastening inflammation resolution, subsiding cytokine storm and decreasing antibiotic requirement that can reduce AMR load are discussed.

13.
Semin Cancer Biol ; 89: 38-60, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36669712

RESUMO

Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Nanomedicina , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Fatores de Transcrição , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Neoplasias/genética
14.
Nutr Cancer ; 75(1): 1-13, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35818029

RESUMO

The tumor microenvironment (TME) is a complex network of cellular and non-cellular components surrounding the tumor. The cellular component includes fibroblasts, adipocytes, endothelial cells, and immune cells, while non-cellular components are tumor vasculature, extracellular matrix and signaling molecules. The tumor cells have constant close interaction with their surrounding TME components that facilitate their growth, survival, and metastasis. Targeting a complex TME network and its interaction with the tumor can offer a novel strategy to disrupt cancer cell progression. Curcumin, from turmeric rhizome, is recognized as a safe and effective natural therapeutic agent against multiple diseases including cancer. Here the effects of curcumin and its metabolites on tumor-TME interaction modulating ability have been described. Curcumin and its metabolites regulate TME by inhibiting the growth of its cellular components such as cancer-associated adipocytes, cancer-associated fibroblast, tumor endothelial cells, tumor-stimulating immune cells, and inducing anticancer immune cells. They also inhibit the interplay of tumor cells to TME by suppressing non-cellular components such as extracellular matrix, and associated tumor promoting signaling-pathways. In addition, curcumin inhibits the inflammatory environment, suppresses angiogenic factors, and increases antioxidant status in TME. Overall, curcumin has the capability to regulate TME components and their interaction with tumor cells.


Assuntos
Curcumina , Neoplasias , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Células Endoteliais , Microambiente Tumoral , Neoplasias/terapia , Fibroblastos/patologia
15.
J Cell Physiol ; 238(1): 32-69, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317692

RESUMO

A type of small noncoding RNAs known as microRNAs (miRNAs) fine-tune gene expression posttranscriptionally by binding to certain messenger RNA targets. Numerous physiological processes in the liver, such as differentiation, proliferation, and apoptosis, are regulated by miRNAs. Additionally, there is growing evidence that miRNAs contribute to liver pathology. Extracellular vesicles like exosomes, which contain secreted miRNAs, may facilitate paracrine and endocrine communication between various tissues by changing the gene expression and function of distal cells. The use of stable miRNAs as noninvasive biomarkers was made possible by the discovery of these molecules in body fluids. Circulating miRNAs reflect the conditions of the liver that are abnormal and may serve as new biomarkers for the early detection, prognosis, and evaluation of liver pathological states. miRNAs are appealing therapeutic targets for a range of liver disease states because altered miRNA expression is associated with deregulation of the liver's metabolism, liver damage, liver fibrosis, and tumor formation. This review provides a comprehensive review and update on miRNAs biogenesis pathways and mechanisms of miRNA-mediated gene silencing. It also outlines how miRNAs affect hepatic cell proliferation, death, and regeneration as well as hepatic detoxification. Additionally, it highlights the diverse functions that miRNAs play in the onset and progression of various liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, fibrosis, hepatitis C virus infection, and hepatocellular carcinoma. Further, it summarizes the diverse liver-specific miRNAs, illustrating the potential merits and possible caveats of their utilization as noninvasive biomarkers and appealing therapeutic targets for liver illnesses.


Assuntos
Biomarcadores , Hepatopatias , Fígado , MicroRNAs , Humanos , Fígado/patologia , Fígado/fisiologia , MicroRNAs/genética , Exossomos , Inativação Gênica , Hepatopatias/patologia
16.
Molecules ; 27(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36432031

RESUMO

Iron oxide nanoparticle (ION)-based ferro-nanofluids (FNs) have been used for different technological applications owing to their excellent magneto-rheological properties. A comprehensive overview of the current advancement of FNs based on IONs for various engineering applications is unquestionably necessary. Hence, in this review article, various important advanced technological applications of ION-based FNs concerning different engineering fields are critically summarized. The chemical engineering applications are mainly focused on mass transfer processes. Similarly, the electrical and electronics engineering applications are mainly focused on magnetic field sensors, FN-based temperature sensors and tilt sensors, microelectromechanical systems (MEMS) and on-chip components, actuators, and cooling for electronic devices and photovoltaic thermal systems. On the other hand, environmental engineering applications encompass water and air purification. Moreover, mechanical engineering or magneto-rheological applications include dampers and sealings. This review article provides up-to-date information related to the technological advancements and emerging trends in ION-based FN research concerning various engineering fields, as well as discusses the challenges and future perspectives.


Assuntos
Eletrônica , Sistemas Microeletromecânicos , Tecnologia , Eletricidade , Nanopartículas Magnéticas de Óxido de Ferro
17.
Semin Cancer Biol ; 86(Pt 2): 54-68, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36087856

RESUMO

Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , DNA , Nanotecnologia/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico
18.
J Nutr Biochem ; 109: 109101, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35777588

RESUMO

Inflammatory bowel disease (IBD) is a chronic disorder associated with the inflammation in the digestive tract. The exact cause of IBD is unknown; nevertheless, in IBD, the homeostasis of key regulatory factors involved in intestinal immunity has been documented to be disrupted. Despite the lack of a viable treatment for IBD, synthetic drugs and monoclonal antibodies are currently used to treat it. However, these treatments have side effects, and the high relapse rate limits their usage. Dietary polyphenols constitute a great variety of compounds and have shown an array of biological properties. Resveratrol is a natural polyphenol found in grapevines and berries. The therapeutic ability of resveratrol against IBD is amply demonstrated in many in vivo studies. Resveratrol can interact with several molecular targets (Nf-kB, SIRT1, mTOR, HIF-1α, miRNAs, and TNF-α) and effectively prevent/ alleviate IBD symptoms with promising results. Although resveratrol has profound anti-inflammatory properties against IBD, its therapeutic employment is limited due to its low water solubility, less chemical stability, less bioavailability, and rapid metabolism in vivo. Hence, resveratrol encapsulation using different carries and its controlled release has become a promising strategy to overcome limitations. Herein, we meticulously review, talk-over the anti-inflammatory effect and mechanisms of resveratrol in IBD. We further provide the latest information on resveratrol formulations and nano-delivery systems used in oral delivery of resveratrol for the treatment of IBD and offer our view on future research on resveratrol in IBD treatment.


Assuntos
Doenças Inflamatórias Intestinais , MicroRNAs , Medicamentos Sintéticos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , MicroRNAs/uso terapêutico , NF-kappa B , Sistemas de Liberação de Fármacos por Nanopartículas , Polifenóis/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Sirtuína 1 , Medicamentos Sintéticos/uso terapêutico , Serina-Treonina Quinases TOR , Fator de Necrose Tumoral alfa , Água
19.
Front Mol Biosci ; 9: 849683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693552

RESUMO

Even though there are a great number of possible conformational states, how a protein generated as a linear unfolded polypeptide efficiently folds into its physiologically active form remained a fascinating and unanswered enigma inside crowded conditions of cells. In this study, various spectroscopic techniques have been exploited to know and understand the effect and mechanism of action of two different sizes of polyethylene glycols, or PEGs (molecular mass ∼10 and ∼20 kilo Daltons, kDa), on cytochrome c (cyt c). The outcomes showed that small size of the PEG leads to perturbation of the protein structure, and conversely, large size of the PEG has stabilizing effect on cyt c. Moreover, binding measurements showed that small size of PEG interacts strongly via soft interactions compared to the larger size of PEG, the latter being governed more by excluded volume effect or preferential exclusion from the protein. Overall, this finding suggests that conformations of protein may be influenced in cellular crowded conditions via interactions which depend upon the size of molecule in the environment. This study proposes that both volume exclusion and soft (chemical) interactions governs the protein's conformation and functional activities. The cellular environment's internal architecture as evident from crowder size and shape in this study has a significant role.

20.
Molecules ; 27(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35164383

RESUMO

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.


Assuntos
Fibronectinas/metabolismo , Doenças Metabólicas/metabolismo , Neoplasias/metabolismo , Animais , Carcinogênese/metabolismo , Exercício Físico , Fibronectinas/análise , Humanos , Doenças Metabólicas/fisiopatologia , Modelos Moleculares , Neoplasias/fisiopatologia , Conformação Proteica , Comportamento Sedentário , Transdução de Sinais
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