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1.
FASEB J ; 38(13): e23813, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38976162

RESUMO

Beta-blockers are commonly used medications that antagonize ß-adrenoceptors, reducing sympathetic nervous system activity. Emerging evidence suggests that beta-blockers may also have anticancer effects and help overcome drug resistance in cancer treatment. This review summarizes the contribution of different isoforms of beta-adrenoceptors in cancer progression, the current preclinical and clinical data on associations between beta-blockers use and cancer outcomes, as well as their ability to enhance responses to chemotherapy and other standard therapies. We discuss proposed mechanisms, including effects on angiogenesis, metastasis, cancer stem cells, and apoptotic pathways. Overall, results from epidemiological studies and small clinical trials largely indicate the beneficial effects of beta-blockers on cancer progression and drug resistance. However, larger randomized controlled trials are needed to firmly establish their clinical efficacy and optimal utilization as adjuvant agents in cancer therapy.


Assuntos
Antagonistas Adrenérgicos beta , Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Animais , Doenças Cardiovasculares/tratamento farmacológico , Progressão da Doença , Receptores Adrenérgicos beta/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
2.
FASEB J ; 38(11): e23734, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38847486

RESUMO

The cell cycle is tightly regulated to ensure controlled cell proliferation. Dysregulation of the cell cycle machinery is a hallmark of cancer that leads to unchecked growth. This review comprehensively analyzes key molecular regulators of the cell cycle and how they contribute to carcinogenesis when mutated or overexpressed. It focuses on cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, checkpoint kinases, and mitotic regulators as therapeutic targets. Promising strategies include CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib for breast cancer treatment. Other possible targets include the anaphase-promoting complex/cyclosome (APC/C), Skp2, p21, and aurora kinase inhibitors. However, challenges with resistance have limited clinical successes so far. Future efforts should focus on combinatorial therapies, next-generation inhibitors, and biomarkers for patient selection. Targeting the cell cycle holds promise but further optimization is necessary to fully exploit it as an anti-cancer strategy across diverse malignancies.


Assuntos
Ciclo Celular , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Animais , Terapia de Alvo Molecular/métodos
3.
FASEB J ; 36(9): e22496, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35947115

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF-κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti-inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200 mg/kg/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO-1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF-κB signaling and its consequent target pro-inflammatory mediators, IL-6 and TNF-α. In contrast, IL-10 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti-inflammatory, antioxidant, and antiapoptotic properties.


Assuntos
Ambroxol , Colite Ulcerativa , Heme Oxigenase-1/metabolismo , Ambroxol/farmacologia , Ambroxol/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose , Colite Ulcerativa/tratamento farmacológico , Colo , Expectorantes/farmacologia , Expectorantes/uso terapêutico , Humanos , Fator 2 Relacionado a NF-E2 , NF-kappa B/farmacologia , Ratos
4.
Int J Mol Sci ; 24(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37445623

RESUMO

Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlining the maximum achievable weight loss. Our aim is to emphasize the active role and main outcomes of GLP-1 agonists in promoting weight loss, as well as in improving hyperglycemia, insulin sensitivity, blood pressure, cardio-metabolic, and renal protection. We highlight the pleiotropic effects of these medications, along with their indications, contraindications, and precautions for both diabetic and non-diabetic patients, based on long-term follow-up studies.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Exenatida , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Peptídeos/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1 , Obesidade/tratamento farmacológico , Obesidade/complicações , Redução de Peso , Liraglutida/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Int J Mol Sci ; 24(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37628857

RESUMO

Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing's syndrome, Basedow-Graves' disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases.


Assuntos
Acromegalia , Neoplasias das Glândulas Suprarrenais , Diabetes Mellitus , Doença de Graves , Resistência à Insulina , Síndrome Metabólica , Humanos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia
6.
Int J Mol Sci ; 24(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36902446

RESUMO

Heat-shock proteins are upregulated in cancer and protect several client proteins from degradation. Therefore, they contribute to tumorigenesis and cancer metastasis by reducing apoptosis and enhancing cell survival and proliferation. These client proteins include the estrogen receptor (ER), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), human epidermal growth factor receptor 2 (HER-2), and cytokine receptors. The diminution of the degradation of these client proteins activates different signaling pathways, such as the PI3K/Akt/NF-κB, Raf/MEK/ERK, and JAK/STAT3 pathways. These pathways contribute to hallmarks of cancer, such as self-sufficiency in growth signaling, an insensitivity to anti-growth signals, the evasion of apoptosis, persistent angiogenesis, tissue invasion and metastasis, and an unbounded capacity for replication. However, the inhibition of HSP90 activity by ganetespib is believed to be a promising strategy in the treatment of cancer because of its low adverse effects compared to other HSP90 inhibitors. Ganetespib is a potential cancer therapy that has shown promise in preclinical tests against various cancers, including lung cancer, prostate cancer, and leukemia. It has also shown strong activity toward breast cancer, non-small cell lung cancer, gastric cancer, and acute myeloid leukemia. Ganetespib has been found to cause apoptosis and growth arrest in these cancer cells, and it is being tested in phase II clinical trials as a first-line therapy for metastatic breast cancer. In this review, we will highlight the mechanism of action of ganetespib and its role in treating cancer based on recent studies.


Assuntos
Antineoplásicos , Proteínas de Choque Térmico HSP90 , Neoplasias , Triazóis , Humanos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Fosfatidilinositol 3-Quinases , Neoplasias/tratamento farmacológico , Triazóis/farmacologia
7.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047011

RESUMO

The number of diabetic patients has risen dramatically in recent decades, owing mostly to the rising incidence of type 2 diabetes mellitus (T2DM). Several oral antidiabetic medications are used for the treatment of T2DM including, α-glucosidases inhibitors, biguanides, sulfonylureas, meglitinides, GLP-1 receptor agonists, PPAR-γ agonists, DDP4 inhibitors, and SGLT2 inhibitors. In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Acetilcolinesterase , Diabetes Mellitus Tipo 2/epidemiologia , Controle Glicêmico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
8.
Molecules ; 28(19)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37836785

RESUMO

With a high number of athletes using sport supplements targeting different results, the need for complex, natural and effective formulations represents an actual reality, while nutrition dosing regimens aiming to sustain the health and performance of athletes are always challenging. In this context, the main goal of this study was to elaborate a novel and complex nutraceutical supplement based on multiple bioactive compounds extracted from Aronia melanocarpa and bee pollen, aiming to support physiological adaptations and to minimize the stress generated by intense physical activity in the case of professional or amateur athletes. Our proposed formulations are based on different combinations of Aronia and bee pollen (A1:P1, A1:P2 and A2:P1), offering personalized supplements designed to fulfill the individual requirements of different categories of athletes. The approximate composition, fatty acid profile, identification and quantification of individual polyphenols, along with the antioxidant capacity of raw biological materials and different formulations, was performed using spectrophotometric methods, GS-MS and HPLC-DAD-MS-ESI+. In terms of antioxidant capacity, our formulations based on different ratios of bee pollen and Aronia were able to act as complex and powerful antioxidant products, highlighted by the synergic or additional effect of the combinations. Overall, the most powerful synergism was obtained for the A1:P2 formulation.


Assuntos
Antioxidantes , Photinia , Animais , Abelhas , Humanos , Antioxidantes/farmacologia , Antioxidantes/análise , Suplementos Nutricionais/análise , Valor Nutritivo , Pólen/química
9.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36361877

RESUMO

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two ß-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the ß-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.


Assuntos
Atenolol , Fatores de Virulência , Camundongos , Animais , Atenolol/farmacologia , Atenolol/metabolismo , Fatores de Virulência/genética , Percepção de Quorum , Biofilmes , Bactérias Gram-Negativas , Pseudomonas aeruginosa , Serratia marcescens/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Proteus mirabilis/metabolismo , Proteínas de Bactérias/metabolismo
10.
Int J Mol Sci ; 23(18)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36142208

RESUMO

Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund's adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat's hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor-kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/metabolismo , Artrite Experimental/metabolismo , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Fibrinolíticos/uso terapêutico , Adjuvante de Freund/efeitos adversos , Sistema Calicreína-Cinina , Ligante RANK/metabolismo , Ratos , Trombina/metabolismo , Receptor 4 Toll-Like/metabolismo
11.
Molecules ; 27(9)2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35566319

RESUMO

At present, the majority of APIs synthesized today remain challenging tasks for formulation development. Many technologies are being utilized or explored for enhancing solubility, such as chemical modification, novel drug delivery systems (microemulsions, nanoparticles, liposomes, etc.), salt formation, and many more. One promising avenue attaining attention presently is supersaturated drug delivery systems. When exposed to gastrointestinal fluids, drug concentration exceeds equilibrium solubility and a supersaturation state is maintained long enough to be absorbed, enhancing bioavailability. In this review, the latest developments in supersaturated drug delivery systems are addressed in depth.


Assuntos
Sistemas de Liberação de Medicamentos , Água , Disponibilidade Biológica , Preparações Farmacêuticas , Solubilidade
12.
Molecules ; 27(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35684455

RESUMO

Neurodegenerative diseases (NDDs) are disorders that affect both the central and peripheral nervous systems. To name a few causes, NDDs can be caused by ischemia, oxidative and endoplasmic reticulum (ER) cell stress, inflammation, abnormal protein deposition in neural tissue, autoimmune-mediated neuron loss, and viral or prion infections. These conditions include Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease (PD). The formation of ß-sheet-rich aggregates of intra- or extracellular proteins in the CNS hallmarks all neurodegenerative proteinopathies. In systemic lupus erythematosus (SLE), numerous organs, including the central nervous system (CNS), are affected. However, the inflammatory process is linked to several neurodegenerative pathways that are linked to depression because of NDDs. Pro-inflammatory signals activated by aging may increase vulnerability to neuropsychiatric disorders. Viruses may increase macrophages and CCR5+ T cells within the CNS during dementia formation and progression. Unlike medical symptoms, which are just signs of a patient's health as expressed and perceived, biomarkers are reproducible and quantitative. Therefore, this current review will highlight and summarize the neurological disorders and their biomarkers.


Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Doenças Neurodegenerativas , Doença de Alzheimer/metabolismo , Biomarcadores , Humanos , Estudos Prospectivos
13.
Molecules ; 27(5)2022 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-35268815

RESUMO

Obesity and diabetes are the most demanding health problems today, and their prevalence, as well as comorbidities, is on the rise all over the world. As time goes on, both are becoming big issues that have a big impact on people's lives. Diabetes is a metabolic and endocrine illness set apart by hyperglycemia and glucose narrow-mindedness because of insulin opposition. Heftiness is a typical, complex, and developing overall wellbeing worry that has for quite some time been connected to significant medical issues in individuals, all things considered. Because of the wide variety and low adverse effects, herbal products are an important hotspot for drug development. Synthetic compounds are not structurally diverse and lack drug-likeness properties. Thus, it is basic to keep on exploring herbal products as possible wellsprings of novel drugs. We conducted this review of the literature by searching Scopus, Science Direct, Elsevier, PubMed, and Web of Science databases. From 1990 until October 2021, research reports, review articles, and original research articles in English are presented. It provides top to bottom data and an examination of plant-inferred compounds that might be utilized against heftiness or potentially hostile to diabetes treatments. Our expanded comprehension of the systems of activity of phytogenic compounds, as an extra examination, could prompt the advancement of remedial methodologies for metabolic diseases. In clinical trials, a huge number of these food kinds or restorative plants, as well as their bioactive compounds, have been shown to be beneficial in the treatment of obesity.


Assuntos
Diabetes Mellitus , Hiperglicemia , Diabetes Mellitus/tratamento farmacológico , Humanos , Insulina/uso terapêutico , Obesidade/tratamento farmacológico
14.
Molecules ; 27(7)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35408561

RESUMO

Breast cancer (BrCa) is the most common malignancy in women and the second most significant cause of death from cancer. BrCa is one of the most challenging malignancies to treat, and it accounts for a large percentage of cancer-related deaths. The number of cases requiring more effective BrCa therapy has increased dramatically. Scientists are looking for more productive agents, such as organic combinations, for BrCa prevention and treatment because most chemotherapeutic agents are linked to cancer metastasis, the resistance of the drugs, and side effects. Natural compounds produced by living organisms promote apoptosis and inhibit metastasis, slowing the spread of cancer. As a result, these compounds may delay the spread of BrCa, enhancing survival rates and reducing the number of deaths caused by BrCa. Several natural compounds inhibit BrCa production while lowering cancer cell proliferation and triggering cell death. Natural compounds, in addition to therapeutic approaches, are efficient and potential agents for treating BrCa. This review highlights the natural compounds demonstrated in various studies to have anticancer properties in BrCa cells. Future research into biological anti-BrCa agents may pave the way for a new era in BrCa treatment, with natural anti-BrCa drugs playing a key role in improving BrCa patient survival rates.


Assuntos
Antineoplásicos , Neoplasias da Mama , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Mama , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Humanos
15.
J Mater Sci Mater Med ; 32(9): 99, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34406523

RESUMO

For bone replacement materials, osteoconductive, osteoinductive, and osteogenic properties are desired. The bacterial resistance and the need for new antibacterial strategies stand among the most challenging tasks of the modern medicine. In this work, brushite cements based on powders of Zinc (Zn) (1.4 wt%) substituted tricalcium phosphate (ß-TCP) and non-substituted ß-TCP were prepared and investigated. Their initial and final phase composition, time of setting, morphology, pH evolution, and compressive strength are reported. After soaking for 60 days in physiological solution, the cements transformed into a mixture of brushite and hydroxyapatite. Antibacterial activity of the cements against Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa bacteria strains was attested. The absence of cytotoxicity of cements was proved for murine fibroblast NCTC L929 cells. Moreover, the cell viability on the ß-TCP cement containing Zn2+ ions was 10% higher compared to the ß-TCP cement without zinc. The developed cements are perspective for applications in orthopedics and traumatology.


Assuntos
Antibacterianos/farmacologia , Cimentos Ósseos , Substitutos Ósseos , Fosfatos de Cálcio/química , Zinco/química , Animais , Sobrevivência Celular , Força Compressiva , Durapatita , Espectroscopia de Ressonância de Spin Eletrônica , Enterococcus faecium , Escherichia coli , Concentração de Íons de Hidrogênio , Íons , Teste de Materiais , Camundongos , Testes de Sensibilidade Microbiana , Ortopedia , Pós , Pseudomonas aeruginosa , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
16.
Molecules ; 26(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641620

RESUMO

The prevalence of Helicobacter pylori infection remains significant worldwide and it depends on many factors: gender, age, socio-economic status, geographic area, diet, and lifestyle. All successful infectious diseases treatments use antibiotic-susceptibility testing, but this strategy is not currently practical for H. pylori and the usual cure rates of H. pylori are lower than other bacterial infections. Actually, there is no treatment that ensures complete eradication of this pathogen. In the context of an alarming increase in resistance to antibiotics (especially to clarithromycin and metronidazole), alternative and complementary options and strategies are taken into consideration. As the success of antibacterial therapy depends not only on the susceptibility to given drugs, but also on the specific doses, formulations, use of adjuvants, treatment duration, and reinfection rates, this review discusses the current therapies for H. pylori treatment along with their advantages and limitations. As an alternative option, this work offers an extensively referenced approach on natural medicines against H. pylori, including the significance of nanotechnology in developing new strategies for treatment of H. pylori infection.


Assuntos
Farmacorresistência Bacteriana , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/genética , Humanos , Nanotecnologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Prevalência
17.
Cureus ; 16(3): e56634, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646213

RESUMO

BACKGROUND AND OBJECTIVES: Advanced osteoarthritis of the knee joint severely affects the patient's mobility, compounded by pre-existing comorbidities such as metabolic preconditioning (such as obesity, dyslipidemia, hyperuricemia, and insulin resistance syndrome) and both type I and type II diabetes. The success of total knee arthroplasty is influenced by knowledge and management of risk factors. The present study aims to evaluate differences in the evolution of risk factors such as obesity, injuries, and sedentary lifestyle, distinguishing those with metabolic preconditions and diabetes. The objectives of our study include (1) investigating the prevalence of obesity among patients, highlighting their proportion in the five categories of body weight; (2) analyzing statistically significant differences between research groups in terms of weight status and physical activity; (3) evaluating postoperative evolution based on the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and without NSAIDs (N-NSAIDs), with an emphasis on overweight patients and those with diabetes; and (4) examining changes in metabolic preconditioning and the incidence of postoperative injury depending on the administration of anti-inflammatory drugs. MATERIALS AND METHODS:  A cohort involving 730 patients diagnosed with gonarthrosis was divided into two groups according to the administration of anti-inflammatory drugs in the first seven postoperative days: N-NSAIDs group (394 patients, 55.3%) and respectively NSAIDs group (319 patients, 44.7%). The prospective, observational study was conducted in terms of risk factors and complications that occurred upon treatment administration in relation to each type of intervention and implant used. The outcomes were assessed in terms of the influence on quality of life, the data being collected and interpreted for the entire cohort, and for each study year individually. RESULTS: The results indicate that almost 69% of them were overweight, while only 31% had a normal weight. Significant differences in weight status were observed between research groups, highlighting the association between obesity and metabolic preconditions or diabetes. Physical activity was absent in a significant proportion, having a notable impact on postoperative evolution, especially in the group without metabolic precondition. Administration of anti-inflammatory drugs influenced postoperative outcomes, with significant differences in overweight and diabetic patients. CONCLUSIONS: The findings suggest the need to manage body weight, promote physical activity, and personalize postoperative treatments, given the complex interactions between obesity, metabolic preconditions, and the administration of NSAIDs.

18.
Int J Gen Med ; 17: 1085-1100, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529101

RESUMO

Purpose: The purpose of this study was to quantify the modifications occurring in osteoporosis at the level of the human proximal femur throughout the trabecular structure, along with the identification of certain anatomic regions preferentially affected by osteoporosis. Another goal was to map the evolution of the radiodensity of the trabecular bone as osteoporosis progresses to an advanced stage. Methods: The study included CT scans (right femur) from 51 patients, out of which 40 had various degrees of osteoporosis, but no other local pathology. Ten regions of interest in two orthogonal slices have been identified and the differences in radiodensity as well as their evolution have been statistically analyzed in terms of relative and absolute changes. Results: A detailed spatial map showing the evolution of osteoporosis was obtained. As osteoporosis evolved, the relative decrease in radiodensity was inversely correlated to the radiodensity of the healthy bone. In particular, the region covering the Ward triangle decreased the most, by an average 61-62% in osteopenia and 101-106% in advanced osteoporosis, while the principal compressive group was affected the least, showing a decrease by an average 14-15% in osteopenia and 29-32% in advanced osteoporosis. The absolute decrease in radiodensity was not correlated to the radiodensity of the healthy bone and was shifted to the inferior-posterior edge of the femur. Inside the femoral head, the upper region was affected the most in absolute terms, while the greater trochanter was less affected than the femoral neck. The maximum metaphyseal cortical bone density was unaffected by the progression of osteoporosis. Conclusion: Significant differences were noticed in terms of the absolute and relative osteoporotic changes in radiodensity related to different anatomical regions of the human femoral bone. These differences become more pronounced as the disease progresses.

19.
In Vivo ; 38(3): 1421-1428, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688601

RESUMO

BACKGROUND/AIM: H. pylori infection can promote a systemic inflammatory syndrome, eventually leading to intestinal metaplasia and gastric cancer. The aim of our study was to investigate the possible association between dyslipidemia and histopathological features of H. pylori gastritis. PATIENTS AND METHODS: An observational, retrospective study was conducted over the period 2017-2022 on symptomatic patients with a positive rapid urease test. A total of 121 patients who underwent upper gastrointestinal endoscopy with stomach biopsy were enrolled in this study. Based on the updated Sydney System, we investigated the association between neutrophils, mononuclear cells, intestinal metaplasia, or gastric atrophy and altered lipid profiles. RESULTS: A high prevalence of H. pylori infection was noticed in the studied group upon the application of the rapid urease test, being associated with dyslipidemia regardless of patient sex. All the endoscopic diagnoses (acute, chronic, or atrophic chronic gastritis, metaplasia) correlated with the histopathological features. Mononuclear cells and metaplasia were more likely to be found in H. pylori-positive patients with dyslipidemia, which is consistent with acute and chronic inflammation caused by H. pylori in the gastric mucosa. CONCLUSION: Although our study was conducted on a small scale, it offers new insights and details regarding H. pylori infection and histopathological features. Mononuclear cells and metaplasia were associated with an altered lipid profile in H. pylori-positive patients. These findings warrant future investigation, such as the evolution of gastric biopsies and lipid profiles before and after eradication.


Assuntos
Mucosa Gástrica , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Centros de Atenção Terciária , Humanos , Infecções por Helicobacter/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Masculino , Feminino , Romênia/epidemiologia , Helicobacter pylori/isolamento & purificação , Pessoa de Meia-Idade , Gastrite/patologia , Gastrite/microbiologia , Mucosa Gástrica/patologia , Mucosa Gástrica/microbiologia , Adulto , Lipídeos/sangue , Lipídeos/análise , Estudos Retrospectivos , Idoso , Metaplasia/patologia , Biópsia , Dislipidemias/patologia , Dislipidemias/sangue
20.
Artigo em Inglês | MEDLINE | ID: mdl-38859783

RESUMO

One of the most common malignancies in women, breast cancer accounts for nearly 25% of all cancer cases. Breast cancer is a diverse cancer form that exhibits variability in both morphology and molecular characteristics, and is linked to numerous risk factors. Although various approaches and research are ongoing in the treatment and prevention of breast cancer, medication resistance in the current breast cancer treatment contributes to the disease's relapse and recurrence. Phytoactive molecules are the subject of growing research in both breast cancer prevention and treatment but currently used conventional medicines and techniques limit their application. Recent years have seen significant advancements in the field of nanotechnology, which has proven to be essential in the fight against drug resistance. The transport of synthetic and natural anticancer molecules via nanocarriers has recently been added to breast cancer therapy, greatly alleviating the constraints of the current approach. In light of these developments, interest in nano-delivery studies of phytoactive molecules has also increased. In this review, research of phytoactive molecules for breast cancers along with their clinical studies and nanoformulations, was presented from current and future perspectives.

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