Cellular and molecular biology最新文献

Pathological cardiac hypertrophy (CH) may lead to heart failure and sudden death. MicroRNAs (miRNAs) have been documented to play crucial parts in CH. The objective of this research was to discuss the potential along with molecule mechanism of miR-495-3p in CH. In vivo CH model was induced by aortic banding (AB) in rats. Cellular hypertrophy in H9c2 rat cardiomyocytes was stimulated by angiotensin II (Ang II) treatment. Haematoxylin and eosin (HE), echocardiography and immunofluorescence staining were used to examine the alterations in cardiac function. The outcomes showed that miR-495-3p expression was high in rat model as well as in Ang II-stimulated cardiomyocytes. Besides, silenced miR-495-3p attenuated CH both in vitro and in vivo. Mechanically, miR-495-3p bound to pumilio RNA binding family member 2 (Pum2) 3'UTR and silenced its expression. Rescue assays further notarized that Pum2 silence abrogated the inhibitory impacts of miR-495-3p inhibitor on CH. In a word, the present research uncovered that miR-495-3p promoted CH by targeting Pum2. Therefore, miR-495-3p may be a novel therapeutic molecule for this disease.

Oral infections can activate local and systemic inflammation. The inflammatory response plays a main role in atherosclerosis. several studies have reported a relation between oral pathogen infection and Atherosclerosis. Recently it was indicated that some oral microbiome has a significant role in triggering atherosclerosis. Denaturing Gradient Gel Electrophoresis (DGGE) is an acceptable assay for identification of uncultivable bacteria. Therefore, we compared the bacterial population diversity in the oral microbiota between atherosclerosis patients and healthy people. Oral microbiota profiling was performed for 139 individuals including 89 patients with CAD and 50 healthy individuals. After DNA extracted from saliva, PCR products were examined and evaluated using DGGE assay. We found that significant relationship between the increased risk of atherosclerosis and the presence of Actinomyces oris, Enterococcus faecalis, Bacterium strain sulresv, Bacterium Culaenoe, NC4, NC7, and NC5 in atherosclerosis patients and healthy individuals. There was also a significant relationship between reducing the risk of atherosclerosis in the presence of NC3 and Entreococcus munotii in atherosclerosis patients and healthy individuals.  In conclusion, presence of some oral microbiota increases the risk of atherosclerosis and the presence of some oral microbiota reduces the risk, so the oral microbiota should be further examined to determine its potential as a biomarker for atherosclerosis.

Multi-drug resistance (MDR) might be acquired by the cancer cells during chemotherapy, and ATP-binding cassette (ABC) transporters play a significant role in MDR. Interferon-γ (IFN-γ) and IFN-β can inhibit cancer cell proliferation; however, the effects and mechanism of these cytokines on the growth and MDR are still unclear. To investigate the effects of IFN-γ and IFN-β, alone or in combination, on viability, resistance, and the expression of ABC transporters of the MDA-MB-231 breast cancer cell line. Using the MDA-MB-231 cell line, we assessed the effects of 20, 100, and 500 IU/ml of IFN-γ and IFN-β, alone or in combination, on cell viability by methyl thiazolyl tetrazolium (MTT) assay; and then we performed the Uptake and Efflux experiment to evaluate the effect of these IFNs on the cell resistance. Then, using quantitative real-time PCR, we evaluated changes in the expression of ABCB1, ABCC1, and ABCG2 mRNA levels. We discovered that IFN-γ and IFN-β might both reduce viability, either alone or in combination. The combination of IFNs also displayed synergistic responses, particularly when utilizing equivalent dosages of 500 or 100 IU/ml. The combination of IFN-γ and IFN-β resulted in a significant increase in Doxorubicin accumulation and down-regulation of the ABCC1 gene at the mRNA level. Our study suggested that equal doses of IFN-γ and IFN-β in combination might result in potentiated responses against cancer, especially, along with chemotherapy agents.

Oxidative stress caused by hyperglycemia can lead to the intensification of hyperglycemia and an increased risk of diabetes complications. Spirulina platensis is a potent free-radical scavenger; it has the potential to be used as a substrate for fermentation by lactic acid bacteria. This study aimed to formulate two functional foods with antioxidant capacity (yogurt containing S. platensis powder / fermented S. platensis powder) for Type 2 Diabetes Mellitus (T2DM) patients and compare the antioxidant effects in diabetic subjects. In this article, for the first time, the antioxidant effect of fermented and non-fermented Spirulina was compared in a clinical study in 'T2DM' patients. By blood sampling, clinical parameters such as FBS, GSH, FRAP, MDA, and CRP before and after each treatment were measured and results were compared between two groups of intervention. Both products as functional foods have a positive effect on the health of diabetic patients by reducing FBS and increasing total antioxidant capacity, and this positive effect is more obvious when yogurt contains fermented lactic acid S. platensis is consumed by T2DM patients.

Congenital heart disease (CHD) is one of the most significant birth defects leading to infant mortality worldwide. Circulating microRNAs (miRNAs) are emerging as novel biomarkers for the detection of cardiovascular diseases. In this study, we aimed to investigate the role of maternal serum miRNAs expression as biomarkers in the diagnosis and prediction of children with CHD. High-throughput sequencing of peripheral blood from pregnant women with abnormal and normal fetal hearts identified 1939 differentially expressed miRNAs, the first 11 of which were selected as predictive biomarkers of CHD. The expression of miRNAs in more clinical samples was then quantitatively verified by reverse transcriptase polymerase chain reaction and the correlation between abnormal miRNAs and CHD was analyzed. Two miRNAs (hsa-miR-3195 and hsa-miR-122-5p) were found to be significantly down-regulated in pregnant women with fetal CHD. By further bioinformatics analysis, we predicted that hsa-miR-3195 and hsa-miR-122-5p could induce CHD by influencing biometabolic processes. hsa-miR-3195 and hsa-miR-122-5p may serve as novel non-invasive biomarkers for prenatal detection of fetal CHD.

Rift Valley Fever Virus (RVFV) is an arbovirus that circulates among animals and can be transmitted to humans. Mosquitoes are the primary vectors that allow RVFV to spread vertically and horizontally. Egypt was exposed to frequent outbreaks with devastating economic consequences. RVFV has a high incidence of worldwide dissemination and no specific vaccine or therapy. Linear Human Cathelicidin (LL-37), is a natural antimicrobial peptide with antiviral activity against numerous viruses. In addition to immunomodulatory effects, LL-37 directly influences viral encapsulation. This study aimed to evaluate the antiviral activity of LL-37 against RVFV in vitro. The post-entry and pre-incubation of LL-37 within Vero cells were assessed in the absence and presence of RVFV. LL-37 activity was assessed using a TCID50 endpoint test, qRT-PCR, and a western blot. When genomic RVFV was quantified, it resulted in a 48% direct inactivation of the viral envelope and a 36% reduction when the virus was pre-incubated with LL-37 before infection. LL-37 decreased viral infection by 75% and protected Vero cells against RVFV infection by 47% at a 1.25 µg/ml dosage. These findings imply that LL-37 exerts antiviral efficacy against RVFV by restricting virus entrance through direct disruption of the virus envelope and indirectly by triggering an immunological response. The effect of LL-37 is time-dependent. As a result, LL-37 may provide rapid and affordable therapies for RVFV infection in Egypt, both during outbreaks and as a preventive strategy.

The diagnosis of familial Mediterranean fever (FMF) is primarily based on clinical standards. The purpose of this study was to investigate the relevance of Mediterranean fever (MEFV) genetic testing in the diagnosis of FMF as well as to identify the most frequent variant alleles and their relationship to clinical symptoms in Egyptian patients. Egyptian patients with a clinical suspicion of having FMF were studied in order to determine MEFV genotypes. Each patient was meticulously evaluated through an extensive collection of their medical history, a thorough clinical examination, and a series of laboratory tests, encompassing CBC, ESR, and CRP measurements. The MEFV variant screening procedure included the use of reverse dot blot hybridization. The average age of our patients when they were given a diagnosis was 22.8 ± 1.404 years old. The predominant clinical manifestations identified were abdominal pain, fever, and arthralgia.  Molecular interrogation of the MEFV gene unveiled that a significant proportion of the cohort, constituting 72 individuals (60%), displayed heterozygosity, whereas a smaller fraction, comprising 12 subjects (10%), demonstrated homozygosity and an equivalent number (10%) exhibited compound heterozygosity. Pertaining to the distribution of allele variants, E148Q emerged as the most prevalent, succeeded by M694I, accounting for 12.5% of the cases, and M680I (G/A), representing 10.41%. This notable prevalence of heterozygous genotypes among the Egyptian demographic, preliminarily identified as potential FMF cases, underscores the imperative for molecular diagnostics to enhance the precision of FMF identification.

Globally, there is a growing concern about tree mortality due to harsh climates and changes in pest and disease patterns. However, experimental studies on the interactions between biotic and abiotic stresses in plants are relatively scarce. In this study, we investigated the interaction between Fusarium solani and water-stressed Dalbergia sissoo saplings. We postulated that under drought conditions, sissoo plants would become more susceptible to dieback infestation. Five fungi, including Fusarium oxysporum, Curvularia lunata, Cladophialophora carrionii, Alternaria alternaria, and Fusarium solani, were isolated from an old shisham tree showing advanced symptoms of dieback infestation. These fungi were identified based on their ITS sequence homology and spore characteristics. Dieback development was more pronounced in plants experiencing water stress, regardless of their predisposition or whether it occurred simultaneously. Lesions were more noticeable and longer in predisposed saplings (3.8cm), followed by simultaneous (2.4cm) and much smaller lesions in seedlings that were inoculated and well-watered (0.24cm). Progressive browning of the upper leaves, which lowers sapling height in predisposed, simultaneous, and well-watered inoculated saplings to 8.09 inches, 5.93 inches, and 17.42 inches, are typical dieback symptoms. Water stress causes the loss of chlorophyll a, b, and carotenoids, which reduces stomatal conductance, transpiration rate, and photosynthetic activity, leading to poor development and mortality. Similarly, predisposed, simultaneous, and well-watered inoculated seedlings expressed increased activity of CAT (22.57, 18.148, and 9.714 U/mg) and POD (3.0, 4.848, 1.246 U/mg), to reduce the damage caused by elevated levels of H2O2 expression. It is concluded that water stress is the main cause of dieback in shisham saplings that subsequently disposed of infected seedlings to secondary agents such as fungi and insects in the advanced stages of the dieback with prolonged drought stress. The lack of dieback in native populations is attributed to the absence of several ecological stresses, including water stress, extended droughts, waterlogging, and salinity. This study emphasizes the need for additional research into the effects of abiotic factors linked with fungal diseases on the long-term production and management of D. sissoo in Pakistan.

Cerebrovascular disease, one of the high-risk diseases worldwide, is high in morbidity, disability, mortality, and recurrence rates, which brings many harms to human beings such as physical and mental harm, economic losses, and impairment of social relations. Cerebral ischemia-reperfusion injury (CIRI) is one of the most common pathological manifestations, with mild hypothermia therapy being the most commonly used treatment in clinical practice. In this study, the research team established a CIRI animal model and found that the neuronal apoptosis rate was significantly increased, accompanied by significant ferroptosis, increased inflammation and oxidative stress damage in brain tissue, and obviously inhibited SIRT1/AMPK pathway. However, after mild hypothermia treatment, the pathological changes of CIRI rats were significantly reversed, and the SIRT1/AMPK pathway was reactivated. Therefore, mild hypothermia may achieve the purpose of CIRI repair by activating the SIRT1/AMPK signaling pathway, and targeted regulation of the SIRT1/AMPK signaling pathway may be a research direction for optimizing mild hypothermia therapy or developing new treatment plans for CIRI.

The mechanism of target interaction involving high-intensity interval training (HIIT) in improving prognosis of myocardial infarction (MI) remains unclear. This study aimed to establish a visual network of "HIIT-target-disease" by referring to the methods of pharmacological disease and drug bioinformatic analysis, to explore the potential targets, and key targets and predict the potential biological mechanism of high-intensity intermittent exercise in preventing and treating myocardial infarction. Public data resources such as OMIM, NCBI and GeneCards were used to find potential targets of high-intensity intermittent exercise and myocardial infarction. Key targets of overlap between exercise and disease were determined according to the Relevance score values analyzed by GeneCards. The visual network diagram of "HIIT - Multi-target-disease" was constructed by Cytoscape. A total of 4820 disease targets and 528 high-intensity intermittent exercise targets were screened out, and 444 overlapped targets were obtained, including 425 protein targets. Five core protein targets were selected: IL10, PPARA, TNF, IL6, and STAT3. It may pass PI3K-AKT signaling pathway, Insulin resistance pathway, T-cell signaling pathway, TNF signaling pathway, and JAX-STAT signaling pathway and other pathways play a role. Our study comprehensively elucidated the potential targets, key targets and molecular mechanisms of high-intensity intermittent exercise in improving the prognosis of myocardial infarction, and proved that high-intensity intermittent exercise can act on multiple targets and multiple pathways to play a good preventive and therapeutic effect on myocardial infarction, providing scientific theoretical basis for revealing the mechanism of high-intensity intermittent exercise in the prevention and treatment of cardiovascular disease.