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1.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 2055-2065, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37837475

RESUMO

Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.


Assuntos
Citosina/análogos & derivados , Mpox , Organofosfonatos , Humanos , Cidofovir , Benzamidas
2.
Artigo em Inglês | MEDLINE | ID: mdl-37650949

RESUMO

Sulfur quantum dots (SQDs) as free heavy metal element quantum dots have promising applications in diagnosis and therapy; however, SQDs' in vivo biodistribution has not been studied. In the current study, SQDs were synthesized directly from cheap sublimated sulfur powder via a one-pot solvothermal method, and sucrose was used as a stabilizer to enhance stability and biocompatibility. The as-obtained SQDs with an average size of 4.6 nm exhibited great water dispersity, highly favorable quantum yield (21.5%), and uniformly spherical shape which were confirmed by UV-Vis, fluorescence spectrophotometer, TEM, and FESEM/EDX/PSA analyses. Moreover, the as-synthesized SQDs had very low cytotoxicity based on cancer (C26) and normal (L929) cell lines via MTT assay. And also, SQDs were radio-labeled directly by Technetium-99m (99mTc), which had good stability ranging from 86 to 99% in PBS and human serum. The SQDs' cell uptake on C26 and L929 cell lines demonstrated that cancer cells had more uptake than normal cells by increasing concentrations. Moreover, SQDs' in vivo biodistribution results displayed high kidney dose accumulation and rapid renal clearance, making them suitable for imaging and therapeutic applications.

3.
Naunyn Schmiedebergs Arch Pharmacol ; 396(11): 2893-2910, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37300702

RESUMO

Genistein, a commonly occurring isoflavone, has recently gained popularity owing to its ever-expanding spectrum of pharmacological benefits. In addition to health benefits such as improved bone health and reduced postmenopausal complications owing to its phytoestrogen properties, it has been widely evaluated for its anti-cancer potential. Several studies have established the potential for its usage in the management of breast, lung, and prostate cancers, and its usage has significantly evolved from early applications in traditional systems of medicine. This review offers an insight into its current status of usage, the chemistry, and pharmacokinetics of the molecule, an exploration of its apoptotic mechanisms in cancer management, and opportunities for synergism to improve therapeutic outcomes. In addition to this, the authors have presented an overview of recent clinical trials, to offer an understanding of contemporary studies and explore prospects for a greater number of focused trials, moving forward. Advancements in the application of nanotechnology as a strategy to improve safety and efficacy have also been highlighted, with a brief discussion of results from safety and toxicology studies.


Assuntos
Isoflavonas , Neoplasias da Próstata , Masculino , Humanos , Genisteína/farmacologia , Genisteína/uso terapêutico , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Fitoestrógenos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Apoptose
4.
Acta Inform Med ; 31(1): 37-40, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37038483

RESUMO

Background: Osteoporosis, demonstrated as an associated disease with more than 30 gene disorders, is a polygenic disorder, and it's also implicated in bone mineral density (BMD) regulations. Lipid peroxidation and hydrogen peroxide levels significantly increased and vice versa the antioxidant enzymes decreased such as Glutathione S-Reductase GSR was found in female postmenopausal females. Objective: This research was done in order to find out the effect of rs2978663 genotypes on the progression of osteoporosis. Methods: First, blood samples were used to extract DNA for analysis. Molecular examination was achieved using PCR, RFLP, and UV imaging after electrophoresis in an agarose gel, and these results were analyzed by SPSS (version 23). Results: The genotypes differed in healthy people, and the proportions varied, as they were: the highest percentage was represented by the GA genotype (78%), followed by the AA genotype (16%), and the GG genotype (6%). For case samples, the highest percentage was represented by the GA genotype (51%), followed by the AA genotype (30%), and the GG genotype (19%). There are significant associations between GA genotype and restriction of fragility disease. The risk of having osteoporosis was significantly lower in those with the GA genotype (OR = 0.1946; 95% CI = 0.04-0.95; P = 0.03). The A allele frequency of the GSR gene (rs2978663) did not change significantly between study groups (OR: 0.9965, 95% CI: 0.5547-1.7816, P value: 0.9905). Conclusion: Overall, it is safe to say that GSR-int3 (rs-2678663) was shown to have no association with osteoporosis in this research of Iraqi women. Inherent variation in the GSR gene (rs-2678663) is associated with decreased osteoporosis risk.

5.
Genes (Basel) ; 14(4)2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-37107577

RESUMO

Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 (FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of FGFR2 (rs1219648, rs2420946, and rs2981582) variants in 446 Bangladeshi women (226 cases and 220 controls). A significant association of the FGFR2 rs1219648 variant with breast malignancy was reported in additive model 1 (aOR = 2.87, p < 0.0001), additive model 2 (aOR = 5.62, p < 0.0001), the dominant model (aOR = 2.87, p < 0.0001), the recessive model (aOR = 4.04, p < 0.0001), and the allelic model (OR = 2.16, p < 0.0001). This investigation also explored the significant association of the rs2981582 variant with the risk of breast cancer in additive model 2 (aOR = 2. 60, p = 0.010), the recessive model (aOR = 2.47, p = 0.006), and the allelic model (OR = 1.39, p = 0.016). However, the FGFR2 rs2420946 polymorphism showed no association with breast cancer except in the overdominant model (aOR = 0.62, p = 0.048). Furthermore, GTT (p < 0.0001) haplotypes showed a correlation with breast cancer risk, and all variants showed strong linkage disequilibrium. Moreover, in silico gene expression analysis showed that the FGFR2 level was upregulated in BC tissues compared to healthy tissues. This study confirms the association of FGFR2 polymorphisms with breast cancer risk.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/patologia , Predisposição Genética para Doença , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene
6.
Int Immunopharmacol ; 118: 109936, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37098654

RESUMO

In RA patients' synovial sites, citrullinated RA-related antigens such as type II collagens, fibrin (ogen), vimentin, and α-enolase could be targeted by ACCPAs. Since ACCPA production can be initiated a long time before RA sign appearance, primary auto-immunization against these citrullinated proteins can be originated from extra-articular sites. It has been shown that there is a significant association between P. gingivalis periodontitis, anti- P. gingivalis antibodies, and RA. P. gingivalis gingipains (Rgp, Kgp) can degrade proteins such as fibrin and α-enolase into some peptides in the form of Arg in the C-terminal which is converted to citrulline by PPAD. Also, PPAD can citrullinate type II collagen and vimentins (SA antigen). P. gingivalis induces inflammation and chemoattraction of immune cells such as neutrophils and macrophages through the increase of C5a (gingipain C5 convertase-like activity) and SCFA secretion. Besides, this microorganism stimulates anoikis, a special type of apoptosis, and NETosis, an antimicrobial form of neutrophil death, leading to the release of PAD1-4, α-enolase, and vimentin from apoptotic cells into the periodontal site. In addition, gingipains can degrade macrophages CD14 and decrease their ability in apoptotic cell removal. Gingipains also can cleave IgGs in the Fc region and transform them into rheumatoid factor (RF) antigens. In the present study, the effects of P. gingivalis on rheumatoid arthritis autoimmune response have been reviewed, which could attract practical insight both in bench and clinic.


Assuntos
Artrite Reumatoide , Periodontite , Humanos , Porphyromonas gingivalis , Autoimunidade , Desiminases de Arginina em Proteínas , Vimentina , Cisteína Endopeptidases Gingipaínas , Fosfopiruvato Hidratase
7.
Naunyn Schmiedebergs Arch Pharmacol ; 396(10): 2179-2196, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37083713

RESUMO

The globe is currently confronting a global fight against the deadliest cancer sickness. Chemotherapy, hormonal therapy, surgery, and radiation therapy are among cancer treatment options. Still, these treatments can induce patient side effects, including recurrence, multidrug resistance, fever, and weakness. As a result, the scientific community is always working on natural phytochemical substances. Numerous phytochemical compounds, including taxol analogues, vinca alkaloids such as vincristine and vinblastine, and podophyllotoxin analogues, are currently undergoing testing and have shown promising results against a number of the deadliest diseases, as well as considerable advantages due to their safety and low cost. According to research, secondary plant metabolites such as myricetin, a flavonoid in berries, herbs, and walnuts, have emerged as valuable bio-agents for cancer prevention. Myricetin and its derivatives have antiinflammatory, anticancer, apoptosis-inducing, and anticarcinogenic properties and can prevent cancer cell proliferation. Multiple studies have found that myricetin has anticancer characteristics in various malignancies, including colon, breast, prostate, bladder, and pancreatic cancers. Current knowledge of the anticancer effects of myricetin reveals its promise as a potentially bioactive chemical produced from plants for the prevention and treatment of cancer. This review aimed to study the numerous bioactivities, mode of action, and modification of several cellular processes that myricetin possesses to impede the spread of cancer cells. This review also addresses the challenges and future prospects of using myricetin as a anticancer drug.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Flavonoides/química , Vincristina/uso terapêutico
8.
Cancers (Basel) ; 15(3)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36765670

RESUMO

Seaweed-derived bioactive compounds are regularly employed to treat human diseases. Sulfated polysaccharides are potent chemotherapeutic or chemopreventive medications since it has been discovered. They have exhibited anti-cancer properties by enhancing immunity and driving apoptosis. Through dynamic modulation of critical intracellular signalling pathways, such as control of ROS generation and preservation of essential cell survival and death processes, sulfated polysaccharides' antioxidant and immunomodulatory potentials contribute to their disease-preventive effectiveness. Sulfated polysaccharides provide low cytotoxicity and good efficacy therapeutic outcomes via dynamic modulation of apoptosis in cancer. Understanding how sulfated polysaccharides affect human cancer cells and their molecular involvement in cell death pathways will showcase a new way of chemoprevention. In this review, the significance of apoptosis and autophagy-modulating sulfated polysaccharides has been emphasized, as well as the future direction of enhanced nano-formulation for greater clinical efficacy. Moreover, this review focuses on the recent findings about the possible mechanisms of chemotherapeutic use of sulfated polysaccharides, their potential as anti-cancer drugs, and proposed mechanisms of action to drive apoptosis in diverse malignancies. Because of their unique physicochemical and biological properties, sulfated polysaccharides are ideal for their bioactive ingredients, which can improve function and application in disease. However, there is a gap in the literature regarding the physicochemical properties and functionalities of sulfated polysaccharides and the use of sulfated polysaccharide-based delivery systems in functional cancer. Furthermore, the preclinical and clinical trials will reveal the drug's efficacy in cancer.

9.
Clin Neurol Neurosurg ; 226: 107599, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36764099

RESUMO

BACKGROUND: Surgical procedures performed in the suboccipital and subtemporal regions are associated with severe pain. The present study was designed to determine pregabalin's effect on postoperative pain in elective craniotomy. METHOD: This double-blind prospective randomized clinical trial was conducted on 50 patients aged 20-60 with ASA classifications I and II. The patients who qualified for elective craniotomies were split into intervention (two capsules =300 mg pregabalin) and control groups (two capsule starch). Patients were also assessed at recovery, 2, 6, 12, and 24 h after surgery for their pain and level of sedation. Data were analyzed by SPSS software version 23, and a P-value ≤ 0.05 was considered significant. RESULTS: The mean pain score in the intervention group was lower than the control group at recovery (p = 0.224), 2 h (p = 0.001), 6 h (p = 0.011), and 12 h (p = 0.032) after surgery. The methadone consumption in the control group was significantly higher than the intervention group (p < 0.05). There was no significant difference between the two groups regarding the level of sedation (p > 0.05). The mean heart rate at induction (p = 0.01), 15 min (p = 0.01), 30 min (p = 0.025), recovery (p = 0.031), and 2 h (p = 0.021) after surgery and the MAP at recovery, 2 h, and 6 h after surgery was significantly lower than the control group (p = 0.029), (p = 0.013), and (p = 0.038), respectively. CONCLUSION: Our investigation demonstrated the effectiveness of pregabalin two hours before surgery on decreasing postoperative pain and analgesic consumption without disturbance in neurological examinations and any specific adverse effects.


Assuntos
Analgésicos , Craniotomia , Humanos , Pregabalina , Estudos Prospectivos , Dor Pós-Operatória , Método Duplo-Cego
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