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1.
Clin Lab ; 70(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38747913

RESUMO

BACKGROUND: The global pandemic, known as the coronavirus disease 2019 (COVID-19) and caused by the severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), poses a significant threat, particularly to individuals with comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), diabetes, HIV, cardiovascular disease (CVD), and cancer. METHODS: This descriptive retrospective study investigates the impact of comorbidities on COVID-19-positive patients. The study includes individuals that were tested positive for SARS-CoV-2 via polymerase chain reaction at the Security Forces Hospital, Makkah, KSA, between February, 2022, and June, 2022. A total of 208 patients (107 males, 101 females) were examined, and the laboratory results revealed normal parameters. RESULTS: An analysis indicates that 86.5% of the patients were discharged, 2.9% remained hospitalized, and 10.6% succumbed to the disease, indicating a 10.6% mortality rate among comorbid COVID-19-positive patients. Notably, the study identifies specific comorbidities (chronic kidney disease, diabetes mellitus, hypertension) and changes in laboratory parameters (red blood cells, hemoglobin, C-reactive protein, white blood cells, ferritin, D-dimer, ALT, troponin, LDH, neutrophils) associated with ICU admission during hospitalization. CONCLUSIONS: This study underscores the critical impact of comorbidities, such as chronic kidney disease, diabetes, and hypertension, on the clinical outcomes of COVID-19-positive patients. The identification of specific laboratory parameters linked with ICU admission provides valuable insights for risk stratification and tailored management strategies.


Assuntos
COVID-19 , Comorbidade , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/sangue , COVID-19/mortalidade , COVID-19/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/sangue , Idoso de 80 Anos ou mais
2.
Thromb J ; 21(1): 115, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37950286

RESUMO

BACKGROUND: Alpha-thalassemia (α-thalassemia) is one of the most common monogenic diseases in Saudi Arabia and is associated with significant morbidity. Premarital testing programs in Saudi Arabia reduce the burden of hemoglobinopathy disorders, and ongoing monitoring is required. We aimed to explore the molecular nature of α-globin genes and identify the most common genotypes and regions with a high risk of α-thalassemia in Saudi Arabia. METHODS: This retrospective study was conducted between January 2021 and December 2022. Six hundred twenty-five samples from patients with microcytic hypochromic anemia in Saudi Arabia were analyzed using reverse dot blot hybridization (RDBH)-based multiplex-PCR, which screens for the known 21 mutations of α-globin genes. RESULTS: Seven mutations in the α-globin gene were identified in 88.96% (556) patients. The most frequent abnormality of a-globin genes was -α3.7 (62.3%), followed by α2IVS1(-5nt) (20.7%) and α2 polyA-1 (α2T.Saudi) (14.1%). Interestingly, α2 polyA-2 (α2T.Turkish) was identified in Saudi and presented with -MED, causing Haemoglobin H disease. The incidence of α-thalassemia in Saudi Arabia's cities showed significant differences (P = 0.004). Jeddah City had the highest percentage of cases (25%), followed by Makkah (23%), Taif (13.3%), and Al-Ahassa (12.4%). CONCLUSION: The study provides current knowledge about the molecular nature of α- thalassemia, highlights the common genotypes that could contribute to disease occurrence in the Saudi population, and sheds light on Saudi regions with a high incidence. It also recommends further studies in a larger population and with differently composed molecular assays to verify these findings.

3.
J Biochem Mol Toxicol ; 37(3): e23275, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36550699

RESUMO

Exposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural-sourced flavonoid with promising antioxidant and anti-inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)-induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO-1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro-oxidants. Moreover, apigenin decreased the elevated pro-inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti-inflammatory, and antiapoptotic effects.


Assuntos
Antioxidantes , Estresse Oxidativo , Animais , Ratos , Masculino , Antioxidantes/farmacologia , Chumbo/toxicidade , Apigenina/farmacologia , Ratos Wistar , Fígado/metabolismo , Anti-Inflamatórios/farmacologia , Acetatos/farmacologia
4.
Environ Res ; 227: 115771, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36967001

RESUMO

Malignant melanoma is the most dangerous type of skin cancer. It is becoming more common globally and is increasingly resistant to treatment options. Despite extensive research into its pathophysiology, there are still no proven cures for metastatic melanoma. Unfortunately, current treatments are frequently ineffective and costly, and have several adverse effects. Natural substances have been extensively researched for their anti-MM capabilities. Chemoprevention and adjuvant therapy with natural products is an emerging strategy to prevent, cure or treat melanoma. Numerous prospective drugs are found in aquatic species, providing a plentiful supply of lead cytotoxic chemicals for cancer treatment. Anticancer peptides are less harmful to healthy cells and cure cancer through several different methods, such as altered cell viability, apoptosis, angiogenesis/metastasis suppression, microtubule balance disturbances and targeting lipid composition of the cancer cell membrane. This review addresses marine peptides as effective and safe treatments for MM and details their molecular mechanisms of action.


Assuntos
Antineoplásicos , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Apoptose , Melanoma Maligno Cutâneo
5.
Environ Toxicol ; 38(2): 266-277, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36447373

RESUMO

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased acetylcholinesterase activity and restored the levels of brain-derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na+ /K+ -ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and caspase-3) levels and increases in anti-apoptotic (Bcl-2) biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Animais , Ratos , Acetilcolinesterase/metabolismo , Cloreto de Alumínio/toxicidade , Cloreto de Alumínio/uso terapêutico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Glutationa/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Prodigiosina/metabolismo , Prodigiosina/farmacologia , Prodigiosina/uso terapêutico
6.
Pharmacol Res ; 184: 106398, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35988867

RESUMO

Abnormalities in the mitogen-activated protein kinase (MAPK) signaling pathway are a key contributor to the carcinogenesis process and have therefore been implicated in several aspects of tumorigenesis, including cell differentiation, proliferation, invasion, angiogenesis, apoptosis, and metastasis. This pathway offers multiple molecular targets that may be modulated for anticancer activity and is of great interest for several malignancies. Polyphenols from various dietary sources have been observed to interfere with certain aspects of this pathway and consequently play a substantial role in the development and progression of cancer by suppressing cell growth, inactivating carcinogens, blocking angiogenesis, causing cell death, and changing immunity. A good number of polyphenolic compounds have shown promising outcomes in numerous pieces of research and are currently being investigated clinically to treat cancer patients. The current study concentrates on the role of the MAPK pathway in the development and metastasis of cancer, with particular emphasis on dietary polyphenolic compounds that influence the different MAPK sub-pathways to obtain an anticancer effect. This study aims to convey an overview of the various aspects of the MAPK pathway in cancer development and invasion, as well as a review of the advances achieved in the development of polyphenols to modulate the MAPK signaling pathway for better treatment of cancer.


Assuntos
Proteínas Quinases Ativadas por Mitógeno , Neoplasias , Apoptose , Carcinogênese/metabolismo , Carcinógenos , Humanos , Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias/tratamento farmacológico , Neovascularização Patológica , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Cell Mol Biol (Noisy-le-grand) ; 67(4): 97-105, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35809298

RESUMO

Traditionally, Viola serpens has been used in the treatment of several human disorders including liver diseases without any scientific evidence. As the current therapies are not very effective and face challenges of unwanted effects and patient compliance, therefore more effective and safe agents are highly needed. The current study aimed to evaluate the hepatoprotective potential of the crude extract and subsequent fractions of the whole plant in the in-vivo model using various hematological and histopathological parameters followed by an HPLC study for the identification of phenolic compounds. Rabbits (1000-1200 g) were used in the study. Paracetamol (2g) was used to induce hepatotoxicity in experimental rabbits. The plant extract was used in two doses (150 and 300 mg/kg body weights) for eight days. The hematological parameters AST, ALT and ALP values were determined along with the histopathology of the liver. Phenolic compounds were identified by high-performance liquid chromatography (HPLC) Agilent-1260 infinity from their retention time, UV spectra and available standards while quantification was done taking the percent peak area. The doses 150 and 300 mg/kg body weight seemed to be more effective. The hematological values and the histopathological slides show the hepatoprotective effect of the plant. Regeneration indicated the presence of nuclei, nuclear cleaning, prominent nucleoli, RBC's, central veins and plates of hepatocytes. The HPLC studies revealed the presence of a number of phenicol compounds. The crude extract and the subsequent fractions of the plant possess strong hepatoprotective activity, providing a scientific rationale for its uses in the treatment of liver toxicities.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Viola , Acetaminofen , Animais , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado , Fenóis/análise , Extratos Vegetais/química , Coelhos
8.
Cell Mol Biol (Noisy-le-grand) ; 68(9): 192-197, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36905283

RESUMO

The current study was planned to examine the nephroprotective effect of the crude extract and its various fractions of Viola serpense Wall against paracetamol-induced toxicity in rabbits. The serum creatinine levels of all fractions, as well as the crude extract, were found to have a greater effect. The effect on urine urea by the n-hexane, ethyl acetate, n-butanol and aqueous fraction in high doses (300 mg/kg b.wt.) and crude extract and chloroform in low doses (150 mg/kg bwts.) were comparatively more effective and comparable to silymarin. The creatinine clearance of the fractions except for chloroform, aqueous at 300 mg/kg and the hydro-methanolic extracts at both doses were highly significant. The histological structures of kidneys in crude extract and chloroform-treated groups showed more improvement at the lower doses. The fractions n-hexane, ethyl acetate and n-butanolic exhibited an inverse dose relationship in the histology of the kidney. However, the aqueous fraction showed a dose-dependent nephroprotective effect. Finally, the crude extract and fractions significantly improved paracetamol-induced nephrotoxicity in rabbits.


Assuntos
Extratos Vegetais , Viola , Animais , Coelhos , Extratos Vegetais/farmacologia , Clorofórmio , Acetaminofen , Água
9.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 27-37, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818275

RESUMO

Fenbfen is used for pain, pyrexia and in the management of osteoarthritis, rheumatoid arthritis and other musculoskeletal disorders. The present research was planned to examine the immunomodulatory activity of fenbufen in different models of cell-mediated immunity (CMI) and humoral immunity (HI). The CMI was evaluated by delayed-type hypersensitivity (DTH) and cyclophosphamide-induced neutropenia assays while HI was appraised by hemagglutination (HA) assay by administering fenbufen at 2, 6 and 10 mg.kg-1 and azathioprine 40 mg.kg-1 (as standard therapy) to albino mice by intraperitoneal route. The ex vivo immunomodulatory action was determined by red blood cell (RBC) membrane stabilization and protein denaturation assays. The results showed that fenbufen treatment had significantly (p<0.05-p<0.001) reduced white blood cells, hemoglobin content, and red blood cells in the healthy and neutropenic mice. A significant (p<0.001) reduction in activities of superoxide dismutase and catalase and glutathione contents, and enhancement of malondialdehyde level were observed in neutropenic mice that were restored by fenbufen treatment. It suppressed DTH reaction after 24, 48 and 72 h post topical application of 2, 4-dinitrofluorobenzene (DNFB). Fenbufen or azathioprine treated groups also showed a significant reduction in the antibody titer against human RBCs induced immune activation in mice as compared to the disease control mice. Fenbufen showed IC50 of 14.0, 50.5 and 66.2 µg.ml-1 whereas, diclofenac sodium showed IC50 of 61.0, 126 and 50.5 µg/ml in RBCs membrane stabilization, egg albumin and bovine serum albumin denaturation assays respectively. The current study shows that fenbufen might have potential immunomodulatory activity against CMI and HI. It can be utilized to treat immune system disorders.


Assuntos
Hipersensibilidade Tardia , Animais , Azatioprina/efeitos adversos , Humanos , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/tratamento farmacológico , Imunidade Celular , Imunidade Humoral , Camundongos , Fenilbutiratos
10.
Cell Mol Biol (Noisy-le-grand) ; 68(10): 15-20, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37114278

RESUMO

The insecticide, cypermethrin, adversely affects biochemical parameters in blood and behavior in grass carp (Ctenopharyngodon idella). Fish were obtained from hatchery, reared in the laboratory. Different concentration of cypermethrin were applied. Blood was collected and hematological and biochemical parameters were measured. Biochemical parameters such as, protein levels, cholesterol, phosphorous and calcium in both acute and chronically cypermethrin treated groups decreased, with increasing exposure time from 24h to 15 days with more pronounced effects in the acute groups. Increased glucose, urea, serum glutamic pyruvic transaminase (SGPT), creatinine, and lactate dehydrogenase (LDH) levels were found in both acute and chronic groups with the increasing exposure time. Hematological parameters, such as red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MHCH), and red cell distribution width (RDW) were significantly reduced in both groups as the exposure time increases. However, the numbers of white blood cells (WBC) and platelets were increased. This study established both the acute and chronic toxicity of cypermethrin in grass carp, which likely occurs secondary to altered biochemical and blood parameters.


Assuntos
Carpas , Hematologia , Animais , Hematócrito , Água Doce
11.
J Biochem Mol Toxicol ; 36(10): e23146, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35698847

RESUMO

Breast cancer is the primary cause of cancer-related death in females, wherein increased mortality of breast cancer patients is recorded worldwide. Zingiberene is a monocyclic sesquiterpene from the ginger plant and has many pharmacological benefits. In this exploration, we assessed the anticancer actions of Zingiberene against the 7,12-dimethylbenz(a)anthracene (DMBA)-stimulated mammary carcinogenesis in rats and MDA-MB-231 cells. Breast cancer was induced in the Female Sprague-Dawley rats through the 25 mg/kg of DMBA in 0.5 ml of corn oil and then treated with 20 and 40 mg/kg of Zingiberene, respectively. The body weight of animals and tumor volume was measured. Hematological parameters, transaminases, lipid profile, lipid peroxidation, and antioxidants status were scrutinized using standard techniques. The estrogen receptor-α and inflammatory markers were inspected by using respective assay kits. Histological damage scores were determined. In vitro experiments were conducted to scrutinize Zingiberene's effect on cell viability and apoptotic cell death in MDA-MB-231 cells. Zingiberene substantially modulated the DMBA-stimulated physiological and hematological changes and decreased the transaminases, and lipid peroxidation in the DMBA-stimulated animals. Zingiberene also elevated the antioxidant level and suppressed the inflammatory markers. Histological study revealed the protective effects of Zingiberene. The viability of MDA-MB-231 cells was noticeably diminished by the Zingiberene, thus inducing apoptotic cell death. Overall, our findings reliably proved the anticancer potential of Zingiberene against the DMBA-stimulated mammary tumorigenesis, and it could be a promising chemotherapeutic agent.


Assuntos
9,10-Dimetil-1,2-benzantraceno , Neoplasias Mamárias Experimentais , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antracenos , Antioxidantes/metabolismo , Carcinógenos , Óleo de Milho/efeitos adversos , Feminino , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/prevenção & controle , Sesquiterpenos Monocíclicos , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio , Transaminases
12.
Med Sci Monit ; 28: e937949, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36284468

RESUMO

BACKGROUND In this study, we aimed to evaluate orthodontic mini-implant placement in the maxillary anterior alveolar region by cone beam computed tomography (CBCT) in 15 patients at a single center in South India. MATERIAL AND METHODS A total of 15 CBCT scans of orthodontic patients after completion of leveling and aligning stage were included. The thickness of labial alveolar bone, labio-palatal bone, and inter-radicular distance between the maxillary central incisors (U1-U1), maxillary central and lateral incisor (U1-U2), and maxillary lateral incisor and canine (U2-U3) at vertical levels 4 mm, 6 mm, and 8 mm above the interdental cementoenamel junction were measured. Descriptive statistics, ANOVA, and Tukey post hoc tests were done to assess the differences among the groups. An independent t test was done to analyze differences by sex. RESULTS The thickness of cortical bone in the labial region was higher in the U2-U3 site than in the U1-U1 site, at a height of 4 mm. Also, there was a significant difference between 4 mm and 8 mm heights in the U2-U3 region. No significant difference was noted in bone dimensions among men and women and in the labio-palatal bone thickness among the different sites. The inter-radicular distance was the highest between the U2-U3 site, while it was the lowest in the U1-U2 site. CONCLUSIONS The findings from this center showed that when CBCT was used to evaluate orthodontic mini-implant placement in the maxillary anterior alveolar region, the U2-U3 and U1-U1 locations at heights between 6 mm to 8 mm apical to the interdental cementoenamel junction were optimal for placement of the mini-implants.


Assuntos
Implantes Dentários , Procedimentos de Ancoragem Ortodôntica , Feminino , Animais , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , Procedimentos de Ancoragem Ortodôntica/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Maxila/diagnóstico por imagem
13.
Mar Drugs ; 20(8)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35892934

RESUMO

Prostate cancer (PCa) is the leading cause of cancer death in men, and its treatment is commonly associated with severe adverse effects. Thus, new treatment modalities are required. In this context, natural compounds have been widely explored for their anti-PCa properties. Aquatic organisms contain numerous potential medications. Anticancer peptides are less toxic to normal cells and provide an efficacious treatment approach via multiple mechanisms, including altered cell viability, apoptosis, cell migration/invasion, suppression of angiogenesis and microtubule balance disturbances. This review sheds light on marine peptides as efficacious and safe therapeutic agents for PCa.


Assuntos
Antineoplásicos , Neoplasias da Próstata , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Organismos Aquáticos/química , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Masculino , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico
14.
Molecules ; 27(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35164185

RESUMO

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Alcaloides/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Descoberta de Drogas , Humanos
15.
Molecules ; 27(13)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35807387

RESUMO

Kaempferol is a natural flavonoid, which has been widely investigated in the treatment of cancer, cardiovascular diseases, metabolic complications, and neurological disorders. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor involved in mediating carcinogenesis and other ailments, playing an important role in regulating oxidative stress. The activation of Nrf2 results in the expression of proteins and cytoprotective enzymes, which provide cellular protection against reactive oxygen species. Phytochemicals, either alone or in combination, have been used to modulate Nrf2 in cancer and other ailments. Among them, kaempferol has been recently explored for its anti-cancer and other anti-disease therapeutic efficacy, targeting Nrf2 modulation. In combating cancer, diabetic complications, metabolic disorders, and neurological disorders, kaempferol has been shown to regulate Nrf2 and reduce redox homeostasis. In this context, this review article highlights the current status of the therapeutic potential of kaempferol by targeting Nrf2 modulation in cancer, diabetic complications, neurological disorders, and cardiovascular disorders. In addition, we provide future perspectives on kaempferol targeting Nrf2 modulation as a potential therapeutic approach.


Assuntos
Complicações do Diabetes , Neoplasias , Doenças do Sistema Nervoso , Humanos , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Estresse Oxidativo , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Transdução de Sinais
16.
Molecules ; 27(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35458669

RESUMO

Cancer is a major health problem across the globe, and is expeditiously growing at a faster rate worldwide. The endoplasmic reticulum (ER) is a membranous cell organelle having inextricable links in cellular homeostasis. Altering ER homeostasis initiates various signaling events known as the unfolded protein response (UPR). The basic purpose of the UPR is to reinstate the homeostasis; however, a continuous UPR can stimulate pathways of cell death, such as apoptosis. As a result, there is great perturbation to target particular signaling pathways of ER stress. Flavonoids have gained significant interest as a potential anticancer agent because of their considerable role in causing cytotoxicity of the cancerous cells. Luteolin, a flavonoid isolated from natural products, is a promising phytochemical used in the treatment of cancer. The current study is designed to review the different endoplasmic reticulum stress pathways involved in the cancer, mechanistic insights of luteolin as an anticancer agent in modulating ER stress, and the available luteolin patent formulations were also highlighted. The patents were selected on the basis of pre-clinical and/or clinical trials, and established antitumor effects using patent databases of FPO IP and Espacenet. The patented formulation of luteolin studied so far has shown promising anticancer potential against different cancer cell lines. However, further research is still required to determine the molecular targets of such bioactive molecules so that they can be used as anticancer drugs.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Estresse do Retículo Endoplasmático , Humanos , Luteolina/farmacologia , Luteolina/uso terapêutico , Neoplasias/tratamento farmacológico , Resposta a Proteínas não Dobradas
17.
Medicina (Kaunas) ; 58(11)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36363467

RESUMO

Background and Objective: Staphylococcus epidermidis is an opportunistic pathogen from pediatric bacteremia that is commonly isolated. Biofilm is the major virulence factor of S. epidermidis; however, the role of biofilm determinants in biofilm formation is highly contradictory and diverse. The current study aimed to investigate the role of polysaccharide-dependent and polysaccharide-independent pathogenic determinants in biofilm formation under physiological stress conditions. Materials and Methods: The isolates (n = 75) were identified and screened for the icaADBC operon, IS256, and an array of MSCRAMMs (Microbial Surface Component Recognizing Adhesive Matrix Molecules) through PCR analysis. The activity of the icaADBC operon was detected by Congo red assay, and the biofilm formation was analyzed through microtiter plate assay. Results: S. epidermidis isolates produced biofilm (n = 65; 86.6%) frequently. The icaA was the major representative module of the actively expressing icaADBC operon (n = 21; 80.7% sensitivity). The MSCRAMMs, including fbe (n = 59; 90.7%; p = 0.007), and embp (n = 57; 87.6%; p = 0.026), were highly prevalent and associated with biofilm positive S. epidermidis. The prevalence of icaADBC operon in biofilm positive and negative S. epidermidis was not significant (n = 41; 63%; p = 0.429). No significant association was found between IS256 and actively complete icaADBC operon (n = 10; 47.6%; p = 0.294). In the presence of 5% human plasma and glucose stress, S. epidermidis produced a strong biofilm (n = 55; 84.6%). Conclusion: The polysaccharide-dependent biofilm formation is significantly replaced (n = 21; 28%; p = 0.149) by a polysaccharide-independent mechanism (n = 59; 90.7%; p = 0.007), in which the MSCRAMMs might actively play their role. The fibrinogen-binding protein and extracellular matrix-binding protein might be potential anti-biofilm drug targets, markers of rapid diagnosis, and potential vaccine candidates of S. epidermidis involved in pediatric bacteremia.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Humanos , Criança , Staphylococcus epidermidis/genética , Paquistão , Óperon/genética , Biofilmes , Polissacarídeos
18.
Medicina (Kaunas) ; 58(10)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36295487

RESUMO

Background and objectives: The study aimed to evaluate and compare the amount of papillary gain and black triangle height reduction after intervention with a microtunnelling technique with either Connective tissue graft (CTG) or Platelet-rich fibrin (PRF) as a biomatrix at 6 months using a microsurgical approach. Materials and Methods: Twenty-six patients with interdental papillary loss were included in the study. The patients were selected randomly for the study groups with thirteen patients in each group: a control group where CTG was utilised as a matrix, and a test group where PRF was utilised as a matrix, for interdental papillary reconstruction. A microtunnelling technique was performed for both the study groups under a surgical microscope. The primary parameters assessed were interdental Papillary height (PH) and Black triangle height (BTH) at baseline, with secondary parameters Visual analogue score by dentist (VAS-D) and patient (VAS-P) assessed at 6 months. Results: Both the control and test groups showed a significant reduction in BTH within their respective group at six months (p < 0.05). The gain in papillary height significantly improved only in the CTG group at 6 months. However, significant differences could not be demonstrated for any of the variables such as BTH (p value = 0.582) and PH (p-value = 0.892) between the study groups at 6 months. Conclusions: IDP reconstruction utilising a microtunnelling approach with CTG or PRF was successful without any significant differences between the groups for the parameters assessed at 6 months.


Assuntos
Retração Gengival , Fibrina Rica em Plaquetas , Humanos , Tecido Conjuntivo/transplante , Retração Gengival/cirurgia , Transplante Autólogo
19.
Medicina (Kaunas) ; 58(10)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36295619

RESUMO

Background and Objectives: The study aimed to compare the mean crestal bone level (CBL) and peri-implant soft tissue parameters in laser micro-grooved (LMG) platform switched implants and abutments (I&A) post 1 year of functional loading among non-diabetic and type II diabetic individuals. Materials and methods: Patients with an edentulous site having minimum bone height and width of ≥13 mm and ≥6 mm, respectively, were divided into two groups: (i) Non-diabetic-8 (control) and (ii) diabetic-8 (test). LMG Implants were placed and loaded immediately with a provisional prosthesis. Mean crestal bone level (MCBL) was evaluated radiographically at baseline and at 1 year. Peri-implant attachment level (PIAL) and relative position of the gingival margin (R-PGM) were recorded. Implant stability quotient (ISQ) level and implant survival rate (ISR) were evaluated at 1 year. Results: Early MCBL within the groups 1 year postloading was similar both mesially and distally (control-0.00 to 0.16 mm and 0.00 to 0.17 mm, respectively; test-0.00 to 0.21 mm and 0.00 to 0.22 mm, respectively) with statistical significance (p ≤ 0.003, p ≤ 0.001 and p ≤ 0.001, p ≤ 0.001, respectively). However, intergroup comparison showed no significant difference statistically in the MCBL in 1 year post functional loading. The peri-implant soft tissue parameters showed no significant difference between the groups. ISQ level between both groups did not reveal any significant changes (p ≤ 0.92), and ISR was 100%. Conclusions: LMG Implants resulted in minimal and comparable early crestal bone loss and soft tissue changes post 1 year of functional loading in moderately controlled diabetic and non-diabetic individuals, suggesting that this could be a reliable system for use in systemically compromised individuals.


Assuntos
Perda do Osso Alveolar , Diabetes Mellitus , Boca Edêntula , Humanos , Lasers , Próteses e Implantes
20.
J Med Virol ; 93(5): 2815-2819, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33128396

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a Betacoronavirus that results in a severe fatal respiratory disease; however, it is also associated with mild inapparent infections. The western part of the Kingdom of Saudi Arabia (KSA) contains the holy places where millions of Muslims gathered from all over the world, all year round, with a high probability of mass disease transmission. The aim of this study was to estimate the prevalence of MERS-CoV among military personnel and their families during the period 2014-2019, in the western part of the KSA. A total of 35,203 sputum samples collected from patients with respiratory distress were screened for the presence of MERS-CoV using real-time reverse-transcription polymerase chain reaction in the examined patients. MERS-CoV infections were detected at a very low percentage in the examined patients. Only 42 of the examined subjects (0.12%) were found positive for MERS-CoV. Most infected cases (32/42) cases were detected in 2014, and the rest of the cases were reported in 2015-2019. The cases with fatal consequences (n = 20) were only detected in 2014. It was concluded that there is a very low prevalence of MERS-CoV infections among the military personnel and their families.


Assuntos
Infecções por Coronavirus/epidemiologia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Militares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/métodos , Síndrome do Desconforto Respiratório/epidemiologia , Arábia Saudita/epidemiologia
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