RESUMO
The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C-reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus-2 is limited and further research is required.
Assuntos
Acetilcisteína , COVID-19 , Sprays Orais , Humanos , Acetilcisteína/administração & dosagem , Acetilcisteína/efeitos adversos , COVID-19/terapia , Tempo de Internação , SARS-CoV-2 , Resultado do Tratamento , Administração por Inalação , Nebulizadores e VaporizadoresRESUMO
Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability.
Assuntos
COVID-19 , Vacinas , Humanos , COVID-19/prevenção & controle , Irã (Geográfico)/epidemiologia , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos de Coortes , Unidades de Terapia IntensivaRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. RESULT: There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. CONCLUSION: This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.
Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Peptidil Dipeptidase A , Antivirais/uso terapêutico , Antivirais/química , Vacinas contra COVID-19RESUMO
Cardiovascular disease is one of the leading causes of mortality globally. Atherosclerosis is an important step towards different types of cardiovascular disease. The role of oxidized low-density lipoprotein (oxLDL) in the initiation and progression of atherosclerosis has been thoroughly investigated in recent years. Moreover, clinical trials have established that diabetic patients are at a greater risk of developing atherosclerotic plaques. Hence, we aimed to review the clinical and experimental impacts of various classes of antidiabetic drugs on the circulating levels of oxLDL. Metformin, pioglitazone, and dipeptidyl peptidase-4 inhibitors were clinically associated with a suppressive effect on oxLDL in patients with impaired glucose tolerance. However, there is an insufficient number of studies that have clinically evaluated the relationship between oxLDL and newer agents such as agonists of glucagon-like peptide 1 receptor or inhibitors of sodium-glucose transport protein 2. Next, we attempted to explore the multitude of mechanisms that antidiabetic agents exert to counter the undesirable effects of oxLDL in macrophages, endothelial cells, and vascular smooth muscle cells. In general, antidiabetic drugs decrease the uptake of oxLDL by vascular cells and reduce subsequent inflammatory signaling, which prevents macrophage adhesion and infiltration. Moreover, these agents suppress the oxLDL-induced transformation of macrophages into foam cells by either inhibiting oxLDL entrance, or by facilitating its efflux. Thus, the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of antidiabetic agents abrogate changes induced by oxLDL, which can be extremely beneficial in controlling atherosclerosis in diabetic patients.
Assuntos
Aterosclerose/prevenção & controle , Hipoglicemiantes/uso terapêutico , Lipoproteínas LDL/sangue , Animais , Humanos , Hipoglicemiantes/farmacologiaRESUMO
The COVID-19 pandemic has plagued the world for more than 1 year now and has resulted in over 77 million cases and 1.7 million related deaths. While we await the rollout of the vaccines, new treatments are urgently needed to reduce the effects of this devastating virus. Here, we describe a number of preclinical studies which show promising effects of the polyphenol resveratrol.
Assuntos
COVID-19 , Humanos , Pandemias , Resveratrol/uso terapêutico , SARS-CoV-2RESUMO
BACKGROUND: Low serum vitamin D level is associated with both high blood pressure and incidence of primary hypertension. Experimental studies suggest that vitamin D supplements may reduce blood pressure. OBJECTIVE: The aim of this study was to investigate whether vitamin D supplementation reduces systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in Iranian patients with essential hypertension. METHOD: A total of 173 patients with essential hypertension participated in this open-label clinical trial. SBP, DBP, and serum vitamin D levels were measured at baseline and at the end of the study. Vitamin D was administered at a dose of 50,000 IU/week, and 1000 IU/day in patients with serum vitamin D levels <20 ng/mL and 20-30 ng/mL, respectively, for 8 weeks. RESULTS: Based on serum vitamin D levels, 45.1%, 17.3%, and 29.5% of patients were deficient, insufficient, and sufficient for vitamin D intake, respectively. Baseline serum levels of vitamin D were not correlated with SBP, DBP, and MAP at the beginning of the study (p = ns). Multiple logistic regression analysis revealed that the risk of vitamin D deficiency was 2.5-fold times higher in women than in men (p = 0.03). After 8 weeks of supplementation with vitamin D, mean SBP and MAP were significantly reduced by 5.5 ± 16.16 (p = 0.01) and 3.7 ± 9.24 (p = 0.004) mmHg, respectively. Neither sex nor age could significantly predict BP response to vitamin D supplementation. CONCLUSION: Vitamin D supplementation may significantly reduce SBP and MAP but not DBP in patients with essential hypertension.
Assuntos
Hipertensão , Vitamina D , Pressão Sanguínea , Suplementos Nutricionais , Hipertensão Essencial , Feminino , Humanos , Hipertensão/tratamento farmacológico , Irã (Geográfico)/epidemiologia , MasculinoRESUMO
Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer worldwide. It metastasizes rapidly and has a poor prognosis. The first-line treatment for most patients is a combination of chemotherapy and radiation. In many subjects, using targeted treatments alongside chemoradiation has shown a better outcome in terms of progression and quality of life for patients. These targeted treatments include small biological inhibiting molecules and monoclonal antibodies. In this review, we have assessed studies focused upon the treatment of non-small cell lung cancer. Some therapies are approved, such as bevacizumab and atezolizumab, while some are still in clinical trials, such as ficlatuzumab and ipilimumab, and others have been rejected due to inadequate disease control, such as figitumumab.
Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de VidaRESUMO
BackgroundFunctional dyspepsia is the main cause of upper abdominal discomfort affecting 5-10% of the world population. Despite various therapeutic approaches, up to 50% of patients with functional dyspepsia seek alternative treatments. In the present study we evaluated the effect of curcumin supplementation along with famotidine therapy on severity of functional dyspepsia. A total of 75 patients with functional dyspepsia according to Rome III criteria were allocated into intervention (N = 39) or control (N = 36) groups. The intervention group was treated with a combination of 500 mg curcumin and 40 mg famotidine daily for 1 month. The control group received placebo and 40 mg famotidine. Severity of dyspepsia symptoms was determined using the Hong Kong questionnaire at baseline, after the 1 month treatment and after a 1 month follow-up. The presence of H. pylori antigens in the stool samples was also investigated in all subjects. No significant difference was observed between intervention and control groups in biochemical indices, severity of dyspepsia and rate of H. pylori infection. A significant decrease was observed in severity of dyspepsia (p < 0.001) and rate of H. pylori infection (p = 0.004) immediately after the treatment and follow-up in the curcumin intervention group. This study indicated that curcumin therapy could be a favorable supplementation in the symptom management of functional dyspepsia. Moreover, curcumin could help efficient eradication of H. pylori in these patients.
Assuntos
Curcumina , Dispepsia , Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/uso terapêutico , Curcumina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Dispepsia/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , HumanosRESUMO
BACKGROUND: Colorectal cancer (CRC) is the third and the fourth most common cancer in Iranian men and women, respectively. Curcuminoids are known to exertprotective effects against several kinds of cancers. We aim to assess the effects of curcuminoids on serum pro- and anti-inflammatory cytokines and quality of life in patients with colorectal cancer undergoing chemotherapy. MATERIAL AND METHODS: This study was a double-blind placebo-controlled trial in patients with CRC (stage 3) aged ≥20 years, who had chemotherapy after the surgery and were referred to Baqiyatallah Oncology Clinic. Patients were randomly assigned to the treatment group receiving curcuminoids capsules (500 mg/day) (n = 36), or the control group taking placebo capsules (n = 36) for 8 weeks. Erythrocyte sedimentation rate (ESR) and serum levels of C-reactive protein (CRP) and 12 pro- and anti-inflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1α (IL-1α), IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP-1), interferon γ (IFN-γ), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF)] were measured at baseline and at the end of the intervention. The EORTC-QLQ-C30 instrument was used to assess the quality of life before and after the intervention. Statistical analyses were performed using SPSS software. RESULTS: A total of 67 subjects completed the study as three and two subjects were lost to follow-up in the curcuminoid and placebo groups, respectively. A significant change in CRP (p = 0.002) and ESR (p = 0.0001) was observed in patients supplemented with curcuminoids at the end of 8 weeks compared to placebo. Moreover, IL-1α showed a decreasing trend after curcuminoid supplementation compared to placebo (p = 0.077). A significant improvement in functional (p = 0.002) and global quality of life (p = 0.020) scales was observed in the curcuminoid group. CONCLUSIONS: The results showed that curcuminoids supplementation for a period of 8 weeks (500 mg/day) can improve ESR and serum levels of CRP in stage-3 CRC subjects and improve the global quality of life and functional scales compared to placebo.
Assuntos
Neoplasias Colorretais , Qualidade de Vida , Neoplasias Colorretais/tratamento farmacológico , Diarileptanoides , Método Duplo-Cego , Feminino , Humanos , Inflamação/tratamento farmacológico , Irã (Geográfico) , Masculino , Fator A de Crescimento do Endotélio VascularRESUMO
OBJECTIVE: To evaluate the safety and efficacy of dietary lentil capsules in patients suffering from dry eye symptoms. METHODS: A randomized, triple-blind, interventional, placebo-controlled study was done. Sixty patients were randomized in two groups to receive either one capsule containing 500 mg of lentil powder or placebo daily for 3 months. UCVA, tear film breakup time (TBUT), Schirmer's test, tear film osmolarity, and OSDI score were recorded at baseline and 3 months after intervention. Data analysis was performed using IBM SPSS for Windows version 20 (SPSS, Chicago, IL, USA). RESULTS: In the lentil group, at baseline, the mean UCVA (LogMAR), OSDI, TBUT (S), tear film osmolarity (mOsm/L), and Schirmer (mm) scores were 0.104 (0.026), 22.66 (19.40), 10.31 (5.32), 301.07 (15.57), and 8.22 (6.87), respectively. These values were 0.101 (0.026), 20.85 (19.44), 13.04 (7.11), 299.81 (11.60), and 9.87 (10.11). In the placebo group, these values were 0.084 (0.027), 25.35 (20.08), 10.56 (4.95), 299.77 (15.09), and 9.35 (8.06) at baseline and 3 months later were 0.077 (0.027), 23.32 (22.90), 13.62 (6.30), 297.54 (12.08), and 8.64 (9.60), respectively. Three patients (one in the lentil group and two in the placebo group) experienced severe gastrointestinal symptoms. CONCLUSION: Although consumption of 500 mg of lentil is safe, this amount is not sufficient for reduction of dry eye syndrome in 3 months. For more validation, a clinical study with increased dosage of lentil is proposed.
Assuntos
Síndromes do Olho Seco , Lens (Planta) , Preparações de Plantas/uso terapêutico , Suplementos Nutricionais , Síndromes do Olho Seco/tratamento farmacológico , Humanos , Concentração Osmolar , LágrimasRESUMO
Anti-arrhythmic agents, like amiodarone, interfere at different stages of the ischemic stroke. However, amiodarone was accompanied with immunological pulmonary complications and adverse neurological effects. We hypothesize that magnesium sulfate in combination with amiodarone holds promise for stroke treatment. Thirty-six patients with confirmed diagnosis of ischemic stroke and atrial fibrillation who received bolus amiodarone were randomly assigned to magnesium sulfate every 24 h or similar volume of normal saline (as placebo) for 5 days. Various severity test scores were used to evaluate the symptoms. Routing biochemistry were also measured at days 1 and 5. Treatment with MgSO4 results in a significant reduction in serum levels of NGAL, Hb, T.Bill, IL-6, IL-8, SNSE, S100B, EGF, PAF, CRP and IgG. Also, MgSO4 treatment significantly improved the RASS, Candida, SOFA, NIHSS and APACHE scores. Moreover, reduction of IL-6, IL-8, SNSE, EGF and APACHE score and increase in RASS score were significantly higher in MgSO4 group compared with placebo. Intravenous administration of MgSO4 in amiodarone-treated stroke patients improved the inflammatory, immunological and neurological indicators and reduced disability in ICU-admitted AIS patients, suggesting that this treatment scheme may prevent amiodarone-induced complications in these patients.
Assuntos
Amiodarona , Acidente Vascular Cerebral , Administração Intravenosa , Antiarrítmicos/uso terapêutico , Humanos , Sulfato de Magnésio/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Curcumin, the active ingredient of the spice turmeric, has been shown to have anticancer activities in several preclinical and clinical studies. The prophylactic effect of curcumin against chemotherapy-induced damage and side effects was evaluated in a double-blind, placebo-controlled randomized trial. Eighty cancer patients on standard chemotherapy regimens were randomly assigned to receive curcumin as adjuvant therapy (500 mg per 12 hours) and matched control group to receive placebo for 9 weeks. Pre- and post-intervention, the changes in the health-related quality-of-Life (QoL) score (based on the University of Washington Quality-of-Life (UW-QoL) questionnaire, version 3), clinical symptoms, and hematological and biochemical parameters were assessed. Comparison between groups based on total QoL score showed that curcumin supplementation was not associated with improved QoL (P = 0.102). Hematological and biochemical analysis showed no statistical differences between the groups at the end of the trial (P > 0.05). However, during the trial, significant differences were observed in hemoglobin (Hb), hematocrit (HCT), lactic acid dehydrogenase (LDH), serum glutamic-oxaloacetic transaminase (SGOT), and anaplastic lymphoma kinase (ALK) between the groups (P < 0.05). Future studies in a larger homogenous population of cancer patients are required to confirm the adjuvant effect of curcumin on chemotherapy-induced QoL.
Assuntos
Antineoplásicos , Curcumina , Antineoplásicos/efeitos adversos , Curcumina/efeitos adversos , Método Duplo-Cego , Humanos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
AIM: We aimed to describe the epidemiological and clinical characteristics of Iranian patients with COVID-19. METHODS: In this single-center and retrospective study, patients with confirmed COVID-19 infections were enrolled. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with outcomes. RESULTS: Of 179 patients with confirmed COVID-19 infection, 12 remained hospitalized at the end of the study and 167 were included in the final analysis. Of these, 153 (91.6%) were discharged and 14 (8.38%) died in hospital. Approximately half (50.9%) of patients suffered from a comorbidity, with diabetes or coronary heart disease being the most common in 20 patients. The most common symptoms on admission were fever, dyspnea, and cough. The mean durations from first symptoms to hospital admission was 8.64 ± 4.14 days, whereas the mean hospitalization time to discharge or death was 5.19 ± 2.42 and 4.35 ± 2.70 days, respectively. There was a significantly higher age in non-survivor patients compared with survivor patients. Multivariate regression showed increasing odds ratio (OR) of in-hospital death associated with respiratory rates >20 breaths/min (OR: 5.14, 95% CI: 1.19-22.15, p = 0.028) and blood urea nitrogen (BUN) >19 mg/dL (OR: 4.54, 95% CI: 1.30-15.85, p = 0.017) on admission. In addition, higher respiratory rate was associated with continuous fever (OR: 4.08, 95% CI: 1.18-14.08, p = 0.026) and other clinical symptoms (OR: 3.52, 95% CI: 1.05-11.87, p = 0.04). CONCLUSION: The potential risk factors including high respiratory rate and BUN levels could help to identify COVID-19 patients with poor prognosis at an early stage in the Iranian population.
Assuntos
COVID-19 , Comorbidade , Hospitalização , Humanos , Irã (Geográfico)/epidemiologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
Autophagy is a self-degradative process that plays a pivotal role in several medical conditions associated with infection, cancer, neurodegeneration, aging, and metabolic disorders. Its interplay with cancer development and treatment resistance is complicated and paramount for drug design since an autophagic response can lead to tumor suppression by enhancing cellular integrity and tumorigenesis by improving tumor cell survival. In addition, autophagy denotes the cellular ability of adapting to stress though it may end up in apoptosis activation when cells are exposed to a very powerful stress. Induction of autophagy is a therapeutic option in cancer and many anticancer drugs have been developed to this aim. Curcumin as a hydrophobic polyphenol compound extracted from the known spice turmeric has different pharmacological effects in both in vitro and in vivo models. Many reports exist reporting that curcumin is capable of triggering autophagy in several cancer cells. In this review, we will focus on how curcumin can target autophagy in different cellular settings that may extend our understanding of new pharmacological agents to overcome relevant diseases.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Autofagia/efeitos dos fármacos , Curcumina/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de SinaisRESUMO
Curcumin, a natural polyphenolic and yellow pigment obtained from the spice turmeric, has strong antioxidative, anti-inflammatory, and antibacterial properties. Due to these properties, curcumin has been used as a remedy for the prevention and treatment of skin aging and disorders such as psoriasis, infection, acne, skin inflammation, and skin cancer. Curcumin has protective effects against skin damage caused by chronic ultraviolet B radiation. One of the challenges in maximizing the therapeutic potential of curcumin is its low bioavailability, limited aqueous solubility, and chemical instability. In this regard, the present review is focused on recent studies concerning the use of curcumin for the treatment of skin diseases, as well as offering new and efficient strategies to optimize its pharmacokinetic profile and increase its bioavailability.
Assuntos
Curcumina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Animais , Disponibilidade Biológica , Curcumina/efeitos adversos , Curcumina/análogos & derivados , Curcumina/farmacocinética , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacocinética , Humanos , Pele/metabolismo , Pele/patologia , Dermatopatias/metabolismo , Dermatopatias/patologia , Resultado do TratamentoRESUMO
Multiple sclerosis (MS) is a disease that has shown a considerable increase in prevalence in recent centuries. Current knowledge about its etiology is incomplete, and therefore it cannot be managed optimally utilizing targeted therapeutic regimens at each stage of the disease. MS progresses in different stages, beginning with a cascade of inflammation. The pivotal spark to initiate this cascade seems to be the migration of Th17 into the central nervous system across the blood-brain barrier (BBB) through the disrupted tight junctions. Coupling of interleukin (IL)-17 and IL-22 to their receptors in the BBB layer facilitates this migration. Subsequently, axon degeneration and the various manifestations of nerve-muscle disorders appear. Curcumin, a major component of turmeric, is derived from Curcuma longa, which belongs to the Zingiberaceae family. Numerous properties of curcumin have been identified recently, some of which can be effective in the treatment of MS, particularly the anti-inflammatory properties via inhibition of secretion of proinflammatory cytokines. In this paper, we will review the various properties and key effects of curcumin for the treatment of MS.
Assuntos
Curcumina/farmacologia , Curcumina/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Curcuma/química , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Esclerose Múltipla/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
BACKGROUND: The discovery of gene- and cell-based strategies has opened a new area to investigate novel approaches for the treatment of many conditions caused by cardiac cell failure. The TBX18 (T-box 18) transcription factor is considered as a prominent factor in the sinoatrial node (SAN) formation during the embryonic development. In this in vitro study, the effect of TBX18 gene expression on human-induced pluripotent-stem-cell-derived cardiomyocytes (hiPS-CMs) to induce pacemaker-like cells was examined. METHODS: The human-dermal-fibroblast-derived iPSCs were transfected using chemical, physical, and Lentiviral methods of TBX18 gene delivery during differentiation into cardiomyocytes (CMs). After the differentiation process through small-molecule-based temporal modulation of the Wnt signaling pathway, the hiPSC-CMs were analyzed using the real-time polymerase chain reaction, immunocytochemistry, immunofluorescence, whole-cell patch-clamp recording, and western blotting to investigate the accuracy of differentiation and identify the effect exerted by TBX18. RESULTS: The hiPS-CMs showed spontaneous beating and expressed specific markers of cardiac cells. The lentiviral-mediated TBX18 delivery was the most efficient method for transfection. The results showed the increment in Connexin 43 expression among untransfected hiPS-CMs, whereas this protein was significantly downregulated followed by TBX18 overexpression. TBX18-hiPSCMs were detected with pacemaker cell features. CONCLUSIONS: It was demonstrated that the TBX18 gene is able to conduct hiPSCs to differentiate into pacemaker-like cells. The TBX18 gene delivery seems to have the potential for the development of biological pacemakers; however, more investigations are still needed to assess its usefulness to fix arrhythmic conditions with SAN failure basis.
Assuntos
Potenciais de Ação , Relógios Biológicos , Diferenciação Celular , Frequência Cardíaca , Células-Tronco Pluripotentes Induzidas/metabolismo , Nó Sinoatrial/metabolismo , Proteínas com Domínio T/metabolismo , Células Cultivadas , Humanos , Fenótipo , Nó Sinoatrial/citologia , Proteínas com Domínio T/genética , Fatores de Tempo , Regulação para Cima , Via de Sinalização WntRESUMO
It is proven that oxidative stress has a pivotal role in the process of neurodegeneration. The use of antioxidants is an attractive method to prevent the incidence of neurodegenerative diseases. We searched major databases (PubMed, Medline, and Google Scholar) using the keywords of neurodegeneration, oxidative stress, and antioxidant for both review and original studies, which have reported the various beneficial effects of antioxidants. About 70 studies were identified for this review. Among various antioxidants, nine antioxidants with the most applications in research investigations were selected and the major findings concerning their protective effects were reviewed. It is concluded that antioxidants can modify and readjust the oxidative stress in the biological milieu, elicit neuroprotective effects, and positively impact the management of neurodegenerative processes.
Assuntos
Antioxidantes/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Antioxidantes/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Keratoconus is a progressive bilateral corneal protrusion that leads to irregular astigmatism and impairment of vision. Keratoconus is an etiologically heterogeneous corneal dystrophy and both environmental and genetic factors play a role in its etiopathogenesis. In this analytical review, we have studied all the genes that are structurally associated with keratoconus and have tried to explain the function of each gene and its association with other eye disorders in a concise way. In addition, using gene set enrichment analysis, it was attempted to find the most important impaired metabolic pathways in keratoconus. Several genetic studies have been carried out on keratoconus and several genes have been identified as risk factors involved in the etiology of the disease. In the current study, 16 studies, including nine association studies, five genome-wide association studies, one linkage study, and one meta-analysis, were reviewed and based on the 19 genes found, enrichment was performed and the most important metabolic pathways involved in the disease were identified. The enrichment results indicated that the two pathways, interleukin 1 processing and assembly of collagen fibrils, are significantly associated with the disease. Obviously, the results of this study, in addition to providing information about the genes involved in the disease, can provide an integrated insight into the gene-based etiology of keratoconus and therapeutic opportunities thereof.
Assuntos
Ceratocone/genética , Transdução de Sinais/genética , Animais , Humanos , Ceratocone/metabolismo , Ceratocone/patologia , Fatores de RiscoRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) as a prevalent hepatic disease is associated with an increased risk of morbidity and mortality related to the liver and cardiovascular disease (CVD). Lifestyle modification and good metabolic control is the first line of treatment, but not always efficacious in reversing NAFLD pathogenesis. Curcumin is a dietary phytochemical with hepatoprotective activities, though its low bioavailability is considered as a major challenge for clinical applications. Therefore, in this study, in order to improve the bioavailability of curcumin, it was coadministered with piperine and we investigated the effects of this bioavailability-enhanced curcumin on serum hepatic enzymes, lipid profile, and glycemic indices in patients with NAFLD. METHODS: In this randomized controlled parallel-group trial, 70 subjects with ultrasound-determined NAFLD were randomized to either 500 mg curcuminoids coadministered with 5 mg piperine daily or placebo for 12 weeks. NAFLD severity (on the basis of sonography) and hepatic function was assessed at baseline and at the study end. RESULTS: Seventy subjects completed the study. Supplementation with curcuminoids plus piperine significantly reduced the hematocrit (P = 0.027), erythrocyte sedimentation rate (P = 0.048) and the serum concentrations of alanine aminotransferase (P = 0.035), aspartate aminotransferase (P = 0.042), alkaline phosphatase (P = 0.004), cholesterol (P < 0.016), low-density lipoprotein cholesterol (P < 0.017), Iron (P = 0.026), and Hemoglobin (P = 0.025) and increased total iron-binding capacity (P = 0.003). However, except albumin, changes in other parameters were not statistically different between groups. In addition, administration of curcuminoids plus piperine significantly improved NAFLD severity (P < 0.001), which was statistically different compared with the placebo group (P = 0.022). Also, the percentage of improved patients was marginally higher in the curcuminoids plus piperine group when compared with the placebo group (P = 0.058). CONCLUSION: This study suggested beneficial effects of combined curcuminoids and piperine supplementation on disease severity in patients with NAFLD.