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BACKGROUND: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. METHODS: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. RESULTS: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 × 10-8 M (45.36 µg/ml) to 6.71 × 10-8 M (26.66 µg/ml) and Ifosfamide from 12.52 × 10-5 M (32.7 µg/ml) to 8.206 × 10-5 M (21.43 µg/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combination treatment. qRT-PCR analysis showed decreased expression of stemness-related genes CD44 and Nanog, and migration-related genes MMP2 and CXCL8 in the combination groups. Apoptosis-related genes Casp-3, Casp-9, and pP53 showed increased expression following combination therapy, while BAX expression increased and BCL2 expression decreased relative to the control. CONCLUSION: The study demonstrates that combining E5-siRNA with Oxaliplatin or Ifosfamide enhances the efficacy of chemotherapy in HPV-16 positive cervical cancer cells. This synergistic approach effectively targets multiple aspects of cancer cell behavior, including proliferation, apoptosis, migration, and stemness. The findings suggest that this combination strategy could potentially allow for lower chemotherapy doses, thereby reducing toxicity while maintaining therapeutic efficacy. This research provides valuable insights into targeting HPV E5 as a complementary approach to existing therapies focused on E6 and E7 oncoproteins, opening new avenues for combination therapies in cervical cancer treatment.
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Apoptosis , Papillomavirus Humano 16 , Ifosfamida , Oxaliplatino , ARN Interferente Pequeño , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Oxaliplatino/farmacología , Femenino , ARN Interferente Pequeño/genética , Línea Celular Tumoral , Ifosfamida/farmacología , Apoptosis/efectos de los fármacos , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Supervivencia Celular/efectos de los fármacos , Proteínas Oncogénicas Virales/genética , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
BACKGROUND: Gastric cancer (GC) is a highly chemoresistant malignancy with a poor prognosis. Paclitaxel's low response rate as second-line chemotherapy for advanced GC has prompted intensive research into its molecular basis and prospective targeted therapies to enhance its therapeutic efficacy. The objective of this study was to investigate the synergistic effects of NRF2 silencing in combination with paclitaxel treatment on GC cell viability, apoptosis, proliferation, autophagy, and migration. METHODS: \After the siRNA-mediated silencing of NRF2 in AGS cells, the transfection efficacy was evaluated by qRT-PCR. The MTT assay was then applied to assess cell viability, followed by flow cytometry analysis for apoptosis, proliferation, and autophagy in AGS cells treated with NRF2 siRNA, paclitaxel, or their combination. Thereafter, the migration of cells was measured using a wound-healing assay. Ultimately, the relative gene expression levels of apoptotic (Bax, Caspase-3, and Caspase-9), anti-apoptotic (Bcl-2), metastatic (MMP-2), and cell cycle (P53) genes were measured by qRT-PCR in all experiment groups to further assess the molecular basis for the combination therapy. RESULTS: NRF2 siRNA transfection significantly enhanced paclitaxel-induced apoptosis and sensitized AGS cells to paclitaxel via modulating the expression of apoptosis-related genes including Bcl-2, Bax, Caspase-3, and Caspase-9. Besides, NRF2 siRNA and paclitaxel synergistically induced cell cycle arrest at the G2 phase, promoted autophagy activation, and inhibited AGS cell migration via MMP-2 downregulation. Additionally, P53, a key regulator of cell growth, was significantly upregulated in the treated groups compared to the control group. CONCLUSIONS: Our findings suggest that paclitaxel combined with siRNA-mediated silencing of NRF2 might represent a promising therapeutic strategy for GC, however further translational and clinical research are warranted.
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BACKGROUND: We sought to conduct this comprehensive systematic review and meta-analysis to assess the prevalence of depression, anxiety, and sleep disturbance in Iranian medical students and resident physicians. METHODS: A systematic search was conducted on 23 December 2023 in PubMed/MEDLINE, Web of Science, Scopus, and Iranian national databases. We pooled the prevalence of individual studies using the random effect model. RESULTS: Our systematic search showed 36 articles that meet the eligibility criteria. Most included studies were cross-sectional. The most used questionnaire to assess depression, anxiety, and sleep disturbance were Beck Depression Inventory (BDI), The Depression, Anxiety and Stress Scale-21 Items (DASS-21), and The Pittsburgh Sleep Quality Index (PSQI), respectively. The overall prevalence of depression, anxiety, and sleep disturbance among Iranian medical students were 43% (95%CI: 33%-53%%, I2 = 98%), 44% (95%CI: 31%-58%%, I2 = 99%), 48% (95%CI: 39%-56%%, I2 = 97%), respectively. The results of subgroup and meta-regression analyses showed questionnaires used and the place of the medical school were significantly associated with the prevalence of aforementioned outcomes. Funnel plot and Begg's regression test did not show a significant source of funnel plot asymmetry for depression, anxiety, and sleep disturbance. CONCLUSION: In conclusion, our study showed that nearly half of the medical students had some type of depression, anxiety, and sleep disturbance problems. To address this serious national public health issue, efficient preventive measures, routine screenings, and prompt interventions are required.
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Ansiedad , Depresión , Trastornos del Sueño-Vigilia , Estudiantes de Medicina , Humanos , Ansiedad/epidemiología , Depresión/epidemiología , Internado y Residencia/estadística & datos numéricos , Irán/epidemiología , Médicos/psicología , Prevalencia , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/psicología , Estudiantes de Medicina/psicología , Encuestas y CuestionariosRESUMEN
Gastric cancer remains a significant health challenge despite advancements in diagnosis and treatment. Early detection is critical to reducing mortality, necessitating the investigation of molecular mechanisms underlying gastric cancer progression. This study focuses on BRD4 expression and its correlation with miR-26a-3p, DLG5-AS1, and JMJD1C-AS1 lncRNAs in gastric cancer. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed significant upregulation of BRD4 in gastric cancer tissues compared to normal tissues, correlating negatively with miR-26a-3p and positively with DLG5-AS1 and JMJD1C-AS1 lncRNAs. Quantitative RT-PCR confirmed these findings in 25 gastric cancer tissue samples and 25 normal samples. BRD4's overexpression was associated with reduced survival rates and older patient age. MiR-26a-3p, a known tumor suppressor, showed decreased expression in gastric cancer tissues, with ROC analysis suggesting it, alongside BRD4, as a potential diagnostic biomarker. Additionally, bioinformatics predicted miR-26a-3p's interaction with BRD4 mRNA. Upregulated lncRNAs DLG5-AS1 and JMJD1C-AS1 likely act as competing endogenous RNAs, sponging miR-26a-3p, thus promoting BRD4 dysregulation. These lncRNAs have not been previously studied in gastric cancer. The findings propose a novel BRD4/lncRNA/miRNA regulatory axis in gastric cancer, highlighting the potential of BRD4, DLG5-AS1, and JMJD1C-AS1 as biomarkers for early diagnosis. Further studies with larger sample sizes and in vivo and in vitro experiments are needed to elucidate this regulatory mechanism's role in gastric cancer progression.
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AIM: To assess the safety and efficacy of a local skin substitute product in the treatment of chronic diabetic foot ulcers (DFUs). MATERIALS AND METHODS: Five patients were evaluated over 6 months. Skin substitutes were applied twice at 2-week intervals. Patients were monitored for any possible adverse effects and wound improvement. RESULTS: The results indicated the overall safety of the skin substitute, with only few adverse effects unrelated to this product. Significant reduction in wound size was observed in four patients during the initial 12-week treatment phase, with complete closure in two patients at 24 weeks. CONCLUSIONS: The application of a bi-layered allogeneic keratinocyte and fibroblast skin substitute in patients with chronic DFU was safe and associated with favourable wound healing results. Adherence to standard treatment protocols, including optimal offloading, is essential to maximize the likelihood of successful wound healing.
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Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.
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Cryoprotective agents play a critical role in minimizing cell damage caused by ice formation during cryopreservation. However, high concentrations of CPAs are toxic to cells and tissues. Required concentrations of CPAs can be reduced by utilizing higher cooling and warming rates, but insight into the thermophysical properties of biological solutions in the vitrification method is necessary for the development of cryopreservation protocols. Most studies on thermophysical properties under ultra-rapid cooling conditions have been qualitatively based on visualization. Differential scanning calorimetry methods are ideal for studying the behavior of biomaterials in various freezing conditions quantitatively and accurately, though previous studies have been predominantly restricted to slower cooling rates. Here, we developed an ultra-rapid cooling method for DSC that can achieve minimal cooling rates exceeding 2000 °C/min. We investigated the thermophysical vitrification behavior of ternary solutions of phosphate buffer saline (1X), dimethyl sulfoxide or glycerol and ice blocking polymers (X-1000 or Z-1000). We quantified the impact of solute concentration on ice crystal formation during rapid cooling. Our findings support the expectation that increasing the solute concentration reduces the amount of ice formation, including devitrification. Devitrification increases from 0 % to 40 % (v/v) Me2SO and then reduces significantly. The relative amounts of devitrification to the total ice formation are 0 %, 60 %, 0 % in 20 %, 40 %, 60 % (v/v) Me2SO, and 2 %, 48 %, 49 % in 20 %, 40 %, 60 % (v/v) glycerol, respectively. The results suggest that at low concentrations, such as below 20 % (v/v) for Me2SO or glycerol, increasing the warming rate after ultra-rapid freezing is not essential to eliminate devitrification. Furthermore, ice blocking polymers do not reduce ice formation substantially and cannot eliminate devitrification under ultra-rapid cooling conditions. In conclusion, our results provide insights into the impact of solute concentration on ice formation and devitrification during rapid cooling, which can be practical for optimizing cryopreservation protocols.
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Rastreo Diferencial de Calorimetría , Criopreservación , Crioprotectores , Dimetilsulfóxido , Glicerol , Vitrificación , Criopreservación/métodos , Crioprotectores/química , Crioprotectores/farmacología , Dimetilsulfóxido/química , Glicerol/química , Glicerol/farmacología , Congelación , HieloRESUMEN
The Hippo signaling pathway has a regulatory function in the organogenesis process and cellular homeostasis, switching the cascade reactions of crucial kinases acts to turn off/on the Hippo pathway, altering the downstream gene expression and thereby regulating proliferation, apoptosis, or stemness. Disruption of this pathway can lead to the occurrence of various disorders and different types of cancer. Recent findings highlight the importance of ncRNAs, such as microRNA, circular RNA, and lncRNAs, in modulating the Hippo pathway. Defects in ncRNAs can disrupt Hippo pathway balance, increasing tumor cells, tumorigenesis, and chemotherapeutic resistance. This review summarizes ncRNAs' inhibitory or stimulatory role in - Hippo pathway regulation in cancer and stem cells. Identifying the relation between ncRNAs and the components of this pathway could pave the way for developing new biomarkers in the treatment and diagnosis of cancers.
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As an aggressive malignancy, glioblastoma multiforme (GBM) is the most common type of brain tumor. The existing treatments have shown limited achievement in increasing the overall survival of patients. Therefore, identifying the key molecules involved in GBM will provide new potential therapeutic targets. Carmustine is an alkylating agent used as a supplementary therapeutic option for GBM. However, the extensive use of carmustine has been limited by uncertainty about its efficacy. MicroRNAs (miRNAs) are essential in post-transcriptional gene regulation. Many aberrantly expressed miRNAs have been detected in various types of human cancer, including GBM. In this study, we evaluated the potential therapeutic effect of miR-143 in combination with carmustine on GBM cells. A172 cells were transfected with miR-143 mimics and then treated with carmustine. To assess the cell viability, apoptosis induction, and cell cycle progression, the MTT assay, Annexin V/PI apoptosis assay, and flow cytometry were used, respectively. Furthermore, qRT-PCR assay was applied to evaluate the expression level of genes related to apoptosis. The obtained results evidenced that miR-143 transfection could promote the sensitivity of A172 cells to carmustine and enhance carmustine-induced apoptosis via modulating the expression levels of Caspase-3, Caspase-9, Bax, and Bcl-2. Also, our results revealed that combination therapy could effectively diminish cell cycle progression in A172 cells. In conclusion, these results confirmed that miR-143 could enhance carmustine-mediated suppression of cell proliferation and improve the chemosensitivity of A172 cells to this chemotherapeutic agent. Therefore, miR-143 combination therapy may be a promising GBM treatment approach.
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OBJECTIVE: This meta-analysis aimed to investigate the effect of dexmedetomidine on brain-derived neurotrophic factor (BDNF) levels in individuals undergoing various medical procedures. We systematically searched electronic databases and manually identified relevant articles to assess the impact of dexmedetomidine on BDNF levels in surgical patients. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Embase, and Web of Science databases with no language restrictions. Studies that examined the effects of dexmedetomidine administration on BDNF levels in surgical patients were included. RESULTS: The overall analysis revealed a statistically significant increase in BDNF levels in individuals receiving dexmedetomidine compared to controls (Standardized Mean Difference SMD = 1.65, 95% CI: 1.02 to 2.28; I2: 89%). Subgroup analyses based on the anesthesia method (p < 0.01), and the type of surgery (p < 0.01) showed significant between-group differences (Fig. 3). The results of the sensitivity analyses indicated that individual studies did not significantly affect the overall results. CONCLUSION: This meta-analysis indicates that dexmedetomidine administration is associated with a significant increase in BDNF levels in individuals undergoing surgical procedures. These findings highlight the potential role of dexmedetomidine in modulating BDNF levels, which may have implications for optimizing perioperative neuroprotective strategies and improving patient outcomes.
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Factor Neurotrófico Derivado del Encéfalo , Dexmedetomidina , Dexmedetomidina/administración & dosificación , Humanos , Factor Neurotrófico Derivado del Encéfalo/sangre , Nootrópicos/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Procedimientos Quirúrgicos OperativosRESUMEN
OBJECTIVE: The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials (RCTs) to evaluate the effectiveness of GC on leptin levels. METHODS: A thorough literature search was carried out using different online databases, including Scopus, Web of Science, PubMed, and Google Scholar, until May 25, 2024. Using random effects, weighted mean differences (WMDs) and corresponding 95 % confidence intervals (CIs) were computed. Standard procedures were followed to account for publication bias, study quality, and statistical heterogeneity. RESULTS: In this meta-analysis, a total of eight eligible trials with 330 participants were ultimately included. Quality assessment showed that half of the included trials were considered to have fair quality, while the other half were deemed to have poor quality. Our analysis, with no indication of publication bias, showed a significantly decreased effect of GC on leptin compared with the placebo (WMD: -5.01 ng/ml; 95 % CI: -9.22 to -0.80, p = 0.02). However, significant heterogeneity was detected between studies (I2 =93.5 %, p < 0.001). The Hartung-Knapp adjustment did not affect our results. Subgroup analysis revealed that GC consumption represents the most effects in trials with sample size ≥ 50 (WMD: -3.63 ng/ml; 95 % CI [-5.51, -1.76], p < 0.001), and mean age of participants ≥ 30 years (WMD: -7.43 ng/ml; 95 % CI [-9.31, -5.56], p < 0.001). CONCLUSIONS: The findings of the present study showed that leptin levels might decline following GC administration. REGISTRATION NUMBER: CRD42023486370.
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Garcinia cambogia , Leptina , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Leptina/sangre , Citratos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
BACKGROUND: A systematic review and meta-analysis have been conducted to evaluate the efficacy of alkalinization for COVID-19 patients based on current evidence to determine the impact of alkalinization on COVID-19 outcomes. METHODS: We searched MEDLINE (Pubmed), Web of Science, Cochrane Library, and Clinicaltrials.gov for studies evaluating the efficacy of alkalinization up to 30 April 2023. Based on the PRISMA 2020 statement criteria a systematic review and meta-analysis of studies were performed. RESULTS: The results of our meta-analysis showed a significant reduction in mortality rate in the alkalinization group compared to controls (RR 0.73, 95% CI: 0.56-0.95; I2 = 0%). However, our subgroup analysis showed no significant improvement in RCT-only studies (RR 0.78, 95% CI: 0.59-1.05; I2 = 0%), the recovery rate was significantly higher in the alkalinization group (RR 2.13, 95% CI: 1.39-3.26; I2 = 0%), duration of recovery also has improved in alkalinization group (SMD 0.76, 95% CI: 0.33-1.18; I2 = 0%). The results of our meta-analysis showed a significant reduction in the duration of hospitalization in the alkalinization group compared to controls with very low certainty of evidence (SMD -0.66, 95% CI: -0.97 to -0.35; I2 = 36%). CONCLUSION: With low certainty of evidence, alkalinization (by sodium bicarbonate) can be an efficient and safe adjuvant treatment for COVID-19 patients. Future randomized controlled trials are needed to strengthen the available evidence.
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COVID-19 , Bicarbonato de Sodio , Humanos , Bicarbonato de Sodio/uso terapéutico , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Resultado del TratamientoRESUMEN
While mortality caused by sepsis remains an unsolved problem, studies showed conflicting results about effectiveness of monoclonal and polyclonal antibodies in patients suffering sepsis. For this reason, this current study provides an update of review clinical randomized trial studies until March 2024. The main object of this study is to determine effects of monoclonal and polyclonal antibodies on mortality rate and hospitalization of patients suffering sepsis. Search of Scopus, Web of science, EMBASE, PubMed and Cochrane were performed and randomized controlled trials which conducted in patients with septic shock or bacterial sepsis were included. Two reviewers assessed all searched trials for eligibility according to already defined criteria and did data collection and analyses afterwards. Present study showed monoclonal and polyclonal antibodies are a safe strategy with mild-to-moderate adverse effects. However, most studies indicate no significant change among inter-and intra-group comparison (p > 0.05) and further studies are needed, results showed an increase in survival rate, ventilator-and ICU-free days, resolve organ dysfunction, mediating inflammation related cytokines.
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Aim: Ursolic acid (UA) has an important biological role in the fight against fat accumulation, insulin resistance, obesity and inflammation. Therefore, in the current review and meta-analysis work, we investigate the effects of UA (dosage range is 50.94 to 450 mg/day) on cardiometabolic risk factors. Materials & methods: After searching the studies up to February 2023, six articles were included in the study. Results: The pooled effect size showed that UA supplementation didn't significantly change body weight, body mass index, waist circumference, body fat percentage, lean body mass, systolic blood pressure, diastolic blood pressure, fasting blood glucose, insulin, triglyceride and high-density lipoprotein compared with control groups. Conclusion: UA supplementation had no significant effect on the cardiometabolic risk factors in adults.
Cardiovascular disease (CVD) is a significant reason for morbidity and mortality. Ursolic acid (UA) has been shown to play important biological roles in the fight against fat accumulation, oxidative stress, insulin resistance via insulin-like growth factor 1, cancer, muscle atrophy, obesity and inflammation responsible for CVD. A systematic review and meta-analysis were conducted up to February 2023; six articles were included in the study and eleven cardiometabolic risk factors were identified. The pooled effect size showed that UA supplementation (dosage range is 50.94 to 450 mg/day) didn't significantly change body weight, body mass index, waist circumference, body fat percentage, lean body mass, systolic blood pressure, diastolic blood pressure, fasting blood glucose, insulin, triglyceride, and high-density lipoprotein compared with control groups.
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Factores de Riesgo Cardiometabólico , Triterpenos , Ácido Ursólico , Humanos , Índice de Masa Corporal , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Suplementos Dietéticos , Triterpenos/farmacología , Triterpenos/uso terapéuticoRESUMEN
Introduction: As the most common aggressive primary brain tumor, glioblastoma is inevitably a recurrent malignancy whose patients' prognosis is poor. miR-143 and miR-145, as tumor suppressor miRNAs, are downregulated through tumorigenesis of multiple human cancers, including glioblastoma. These two miRNAs regulate numerous cellular processes, such as proliferation and migration. This research was intended to explore the simultaneous replacement effect of miR-143, and miR-145 on in vitro tumorgenicity of U87 glioblastoma cells. Methods: U87 cells were cultured, and transfected with miR-143-5p and miR-145-5p. Afterward, the changes in cell viability, and apoptosis induction were determined by MTT assay and Annexin V/PI staining. The accumulation of cells at the cell cycle phases was assessed using the flow cytometry. Wound healing and colony formation assays were performed to study cell migration. qRT-PCR and western blot techniques were utilized to quantify gene expression levels. Results: Our results showed that miR-143-5p and 145-5p exogenous upregulation cooperatively diminished cell viability, and enhanced U-87 cell apoptosis by modulating Caspase-3/8/9, Bax, and Bcl-2 protein expression. The combination therapy increased accumulation of cells at the sub-G1 phase by modulating CDK1, Cyclin D1, and P53 protein expression. miR-143/145-5p significantly decreased cell migration, and reduced colony formation ability by the downregulation of c-Myc and CD44 gene expression. Furthermore, the results showed the combination therapy of these miRNAs could remarkably downregulate phosphorylated-AKT expression levels. Conclusion: In conclusion, miR-143 and miR-145 were indicated to show cooperative anti- cancer effects on glioblastoma cells via modulating AKT signaling as a new therapeutic approach.
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BACKGROUND: Uropathogenic Escherichia coli (UPEC) isolates, have a wide variety of virulence factors to promote colonization and survival in the urinary tract. This study aimed to evaluate adhesin genes, biofilm formation ability, antibiotic resistance profiles of UPEC strains, and the related risk factors in patients with UTIs caused by drug-resistant UPEC. METHODOLOGY: A total of 105 UPEC isolates were evaluated for biofilm formation using 96-well microtiter plates, the presence of adhesin genes by PCR assay and the antimicrobial susceptibility pattern using the disk diffusion method. Demographic and clinical characteristics of patients were investigated to identify predisposing factors for drug-resistant isolates. RESULTS: Out of 105 UPEC isolates, 84.8% were positive for biofilm formation. Biofilm-producing isolates exhibited a significantly higher prevalence of fimH, kpsMTII, csgA, afa/draBC, and pap adhesin genes compared to non-biofilm-producing strains (p < 0.05). The results also revealed that 52.4% of the isolates were ESBL-producing, and 84.8% were multidrug-resistant (MDR). Further analysis of antibiotic susceptibility among ESBL-producing strains showed the highest resistance rates to ampicillin, ciprofloxacin, and trimethoprim-sulfamethoxazole. Conversely, the highest susceptibility, in addition to carbapenems, was observed for fosfomycin, amikacin, cefoxitin, and nitrofurantoin. We identified hypertension as a potential risk factor for infection with ESBL-producing UPEC strains. CONCLUSIONS: Our results revealed a significant rate of drug resistance among UPEC isolates obtained from UTIs in our region. This underscores the importance of monitoring the empirical use of antibiotics and identifying specific risk factors in our geographical area to guide the selection of appropriate empirical treatment for UTIs.
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Biopelículas , Infecciones por Escherichia coli , Infecciones Urinarias , Escherichia coli Uropatógena , Humanos , Irán/epidemiología , Escherichia coli Uropatógena/genética , Escherichia coli Uropatógena/efectos de los fármacos , Infecciones Urinarias/microbiología , Infecciones Urinarias/epidemiología , Femenino , Factores de Riesgo , Masculino , Biopelículas/crecimiento & desarrollo , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/epidemiología , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Factores de Virulencia/genética , Adhesinas de Escherichia coli/genética , Adolescente , Niño , Adhesinas Bacterianas/genética , Anciano de 80 o más Años , Farmacorresistencia Bacteriana Múltiple/genética , Reacción en Cadena de la Polimerasa , PreescolarRESUMEN
BACKGROUND: Obesity is a global health concern, and understanding its prevalence among medical students is crucial for shaping targeted interventions. This systematic review and meta-analysis aim to comprehensively assess the prevalence of obesity and overweight among medical students. METHODS: A systematic literature search was conducted across major databases, including PubMed, Scopus, and Web of Science, in order to identify relevant studies that evaluated obesity and overweight among medical students. Inclusion criteria encompassed published and peer-reviewed studies reporting the prevalence of obesity among medical students. RESULTS: A total of 1245 studies were screened based on their titles and abstracts, and 99 studies comprised a total sample size of 47,455 medical students across diverse geographical regions were included in this study. The overall pooled prevalence of overweight among medical students was estimated at 18% (95% CI: 17%-20%), with obesity at 9% (95% CI: 7%-11%). The combined prevalence of excess weight (overweight and obesity) was calculated to be 24% (95% CI: 22%-27%). Meta-regression results indicated a significant correlation between study year and overweight/obesity prevalence (p < 0.05), with a trend towards increasing prevalence over time. Male medical students exhibited a higher pooled prevalence, increasing with the percentage of male participants. CONCLUSION: This systematic review and meta-analysis provide a comprehensive overview of the prevalence of obesity among medical students globally. In summary, obesity and overweight present a substantial worldwide health concern, especially among susceptible groups such as medical students, whose prevalence is on the rise. It is crucial to grasp the extent and contributing factors of obesity among medical students to formulate precise interventions aimed at fostering healthier habits and alleviating the adverse impacts of obesity on both physical and mental health.
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Salud Global , Obesidad , Sobrepeso , Estudiantes de Medicina , Humanos , Estudiantes de Medicina/estadística & datos numéricos , Estudiantes de Medicina/psicología , Prevalencia , Obesidad/epidemiología , Sobrepeso/epidemiología , Salud Global/estadística & datos numéricos , Masculino , FemeninoRESUMEN
Gastric cancer, as the fifth most frequent disease and the fourth foremost cause of cancer-related death worldwide, remains a main clinical challenge due to its poor prognosis, limited treatment choices, and ability to metastasize. Combining siRNAs to suppress lncRNA with chemotherapeutic medications is a novel treatment approach that eventually increases the therapeutic efficacy of the drug while lessening its adverse effects. This study was performed with the purpose of examining the impact of inhibiting DLGAP1-AS2 expression on gastric cancer cells' drug chemosensitivity. AGS cells were cultured as the study cell line and were transfected with an optimum dose of DLGAP1-AS2 siRNA and then treated with oxaliplatin. Cell viability was examined using the MTT technique. Apoptosis and cell cycle were evaluated using Annexin V/PI staining and flow cytometry. Later, the scratch test was conducted to investigate the ability of cells to migrate, and the inhibition of the stemness of AGS cells was further investigated through the colony formation method. Finally, the qRT-PCR technique was used to assess the expression of Bax, Bcl-2, Caspase-3, p53, MMP-2, and CD44 genes. The MTT test indicated the effect of gene therapy with siRNA and oxaliplatin in combination reduced the chemotherapy drug dose to 29.92 µM and increased AGS cells' sensitivity to oxaliplatin. Also, the combination therapy caused a significant increase in apoptosis. However, it reduced the stemness feature, the rate of cell viability, proliferation, and metastasis compared to the effect of each treatment alone; the results also showed the arrest of the cell cycle in the Sub G1 phase after the combined treatment and a further reduction in the number and size of the formed colonies. Suppressing the expression of lncRNA DLGAP1-AS2 by siRNA followed by treatment with oxaliplatin can be utilized as an effective and new therapeutic technique for gastric cancer therapy.
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BACKGROUND: The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in patients with T1DM, using a systematic review and meta-analysis approach. METHODS: We systematically searched multiple databases including Medline, Scopus, and others up to 10 January 2024, without language or regional restrictions. We included randomized controlled trials (RCTs) comparing teplizumab with placebo in T1DM patients. RESULTS: Our analysis incorporated 8 RCTs, predominantly involving participants aged 7-35 years, diagnosed with T1DM and treated with 14-day courses of teplizumab. The primary outcomes included insulin use, C-peptide levels, and HbA1c levels. We observed a significant reduction in insulin use in the teplizumab group standardised mean difference of -0.50 (95% Confidence Interval [CI]: -0.76 to -0.23, p < 0.001; I2 = 49%). C-peptide levels were consistently higher in the teplizumab group, indicating improved endogenous insulin production. However, no significant change was noted in HbA1c levels between the groups. Quality assessment indicated a low risk of bias in most studies. CONCLUSIONS: Teplizumab has a significant impact on reducing insulin dependence and enhancing endogenous insulin production in T1DM patients. However, its effect on long-term glycaemic control, as indicated by HbA1c levels, remains inconclusive.
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Anticuerpos Monoclonales Humanizados , Diabetes Mellitus Tipo 1 , Ensayos Clínicos Controlados Aleatorios como Asunto , Adolescente , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Pronóstico , Resultado del Tratamiento , Niño , Adulto Joven , AdultoRESUMEN
Previous studies have assessed how supplementing with policosanol affects blood sugar levels. The outcomes, nevertheless, were not constant. Multiple electronic databases were searched including ISI Web of Science, Cochrane Library, PubMed, Google Scholar, and Scopus until February 9, 2023. To assess the effects of policosanol on glucose, we employed a random-effects or fixed-effects meta-analysis approach to examine the weighted mean differences (WMDs) and associated 95 % confidence intervals (CI) before and after policosanol and placebo administration. The final analysis comprised a total of 25 trials with 2680 participants. Compared to the control group, policosanol supplementation significantly reduced blood glucose levels (WMD: -2.24 mg/dl; 95 % CI: -4.05, -0.42, P = 0.01). Findings from subgroup analysis revealed a significant reduction of policosanol supplementation on glucose levels in period of less than 24 weeks, and in individuals below 50 years of age. Additionally, the reduction was statistically significant in dosage of 10 mg/day. Our dose-response analysis indicates no evidence of a non-linear relationship between policosanol dose and duration and changes in glucose levels (P-nonlinearity = 0.52, and P-nonlinearity = 0.52, respectively). Policosanol supplementation might improve blood glucose. Further trials with more complex designs are required to confirm the findings.