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Both c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS) play important roles in myocardial ischemia/reperfusion (I/R) injury. Our previous studies suggest that N-n-butyl haloperidol iodide (F2) exerts cardioprotection by reducing ROS production and JNK activation caused by I/R. In this study, we hypothesized that there is a JNK/Sab/Src/ROS pathway in the mitochondria in H9c2 cells following hypoxia/reoxygenation (H/R) that induces oxidative stress in the mitochondria and that F2 exerts mitochondrial protective effects during H/R injury by modulating this pathway. The results showed that H/R induced higher-level ROS in the cytoplasm on the one hand and JNK activation and translocation to the mitochondria by colocalization with Sab on the other. Moreover, H/R resulted in mitochondrial Src dephosphorylation, and subsequently, oxidative stress evidenced by the increase in ROS generation and oxidized cardiolipin in the mitochondrial membranes and by the decrease in mitochondrial superoxide dismutase activity and membrane potential. Furthermore, treatment with a JNK inhibitor or Sab small interfering RNA inhibited the mitochondrial translocation of p-JNK, decreased colocalization of p-JNK and Sab on the mitochondria, and reduced Src dephosphorylation and mitochondrial oxidative stress during H/R. In addition, Src dephosphorylation by inhibitor PP2 increased mitochondrial ROS production. F2, like inhibitors of the JNK/Sab/Src/ROS pathway, downregulated the H/R-induced mitochondrial translocation of p-JNK and the colocalization of p-JNK and Sab on the mitochondria, increased Src phosphorylation, and alleviated the above-mentioned mitochondrial oxidative stress. In conclusion, F2 could ameliorate H/R-associated oxidative stress in mitochondria in H9c2 cells through the mitochondrial JNK/Sab/Src/ROS pathway.
Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects. Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats. Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each. Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days. The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose. The blood samples were taken 24 h after the last dose of ISO. The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups. All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP. All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment. CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES) after MI. MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC. CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination. Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction.
Background: Thalassemia patients need repeated transfusion that lead to increased blood ferritin level and iron overload in the heart and liver. Because the roles of hepcidin antimicrobial peptide (HAMP) and hemocromatosis protein (HFE) in iron metabolism have been confirmed, this study investigated the effects of these gene's polymorphisms on blood ferritin levels and iron overload in the heart and liver in patients with beta thalassemia major Materials and Methods: This cross-sectional study was conducted on 91 patients referring to the Hajar Hospital in Shahrekord, Iran in 2015. After the blood samples were collected, the ferritin levels were measured, DNA was extracted from the blood cells, and the types of polymorphisms were determined using PCR-RFLP. Data of MRI T2* in the heart and liver were drawn from the patients' medical files. Data analysis was conducted by t-test, chi-square test, Fisher's exact test, and Pearson correlation coefficient. Results: There was no significant correlation between blood ferritin level and c.-582 A>G polymorphisms of hepcidin gene (p=0.58), and H63D of HFE gene (p=0.818). In addition, there was no significant association between the polymorphisms and heart and liver MRI, but there was a significant association between blood ferritin level and qualitative heart and liver MRI (r=-0.34, p=0.035 and r=-0.001, p=0.609, respectively). Conclusion: In patients with β-thalassemia major, the presence of c.-582A>G HAMP and H63D HFE polymorphisms is not effective on blood ferritin level and iron overload in the heart and liver in the studied region.
Numerous approaches have been introduced to regenerate artificial dental tissues. However, conventional approaches are limited when producing a construct with three-dimensional patient-specific shapes and compositions of heterogeneous dental tissue. In this research, bioprinting technology was applied to produce a three-dimensional dentin-pulp complex with patient-specific shapes by inducing localized differentiation of human dental pulp stem cells within a single structure. A fibrin-based bio-ink was designed for bioprinting with the human dental pulp stem cells. The effects of fibrinogen concentration within the bio-ink were investigated in terms of printability, human dental pulp stem cell compatibility, and differentiation. The results show that micro-patterns with human dental pulp stem cells could be achieved with more than 88% viability. Its odontogenic differentiation was also regulated according to the fibrinogen concentration. Based on these results, a dentin-pulp complex having patient-specific shape was produced by co-printing the human dental pulp stem cell-laden bio-inks with polycaprolactone, which is a bio-thermoplastic used for producing the overall shape. After culturing with differentiation medium for 15 days, localized differentiation of human dental pulp stem cells in the outer region of the three-dimensional cellular construct was successfully achieved with localized mineralization. This result demonstrates the possibility to produce patient-specific composite tissues for tooth tissue engineering using three-dimensional bioprinting technology.
Adult tissue stem cells have shown promise for the treatment of debilitating tendon injuries. However, few comparisons of stem cells from different tissue sources have been made to determine the optimum stem cell source for treating tendon. Moreover, it is likely that the application of tenogenic growth factors will improve tendon stem cell treatments further, and a comprehensive comparison of a number of growth factors is needed. Thus far, different types of stem cells cannot be evaluated in a high-throughput manner. To this end, we have developed an approach to culture mesenchymal stem cells isolated from bone marrow in collagen type I hydrogels with tenogenic growth factors using economical, commercially available supplies. To optimize growth factors for this assay, FGF-2, TGF-β1, IGF-1, and/or BMP-12 were tested singly and in novel combinations of (1) BMP-12 and IGF-1, (2) TGF-β1 and IGF-1, and/or (3) BMP-12 and FGF-2 over 10 days. Our data suggest that BMP-12 supplementation alone results in the strongest expression of tendon marker genes, controlled contractility of constructs, a higher degree of cell alignment, and tendon-like tissue morphology. This easy-to-use benchtop assay can be used to screen novel sources of stem cells and cell lines for tissue engineering and tendon healing applications.
Senility death is defined as natural death in the elderly who do not have a cause of death to be described otherwise and, if human life is finite, it may be one of the ultimate goals of medicine and healthcare. A recent survey in Japan reports that municipalities with a high senility death ratio have lower healthcare costs per late-elderly person. However, the causes of regional differences in senility death ratio and their biomedical determinants were unknown. In this study, we examined the relationships of the regional difference in senility death ratio with the regional differences in heart rate variability and physical activity.
Colostrum is the primary source of maternal immunoglobulin A (IgA) for the newborn. IgA participates in protection and regulation mechanisms of the immune response at the neonate's mucosa. Several studies have evaluated infectious diseases and vaccine protocols effects during pregnancy on maternal milk IgA levels, with the aim to understand lactation protecting effect on newborn. However, most of their results demonstrated that there were no differences in the total IgA levels. In humans, IgA has two subclasses (IgA1 and IgA2), they have an anatomical distribution among mucosal compartments, their levels vary after antigen stimulation and are also seen to describe differential affinities in colostrum. Although there are differences between IgA subclasses in several compartments, these studies have excluded specific colostrum IgA1 and IgA2 determination.
Sports-related concussion (SRC) is a recognised risk in road cycling and can have serious health consequences. Recent high-profile cases of professional road cyclists continuing to participate in races despite suffering obvious SRC have highlighted the difficulties in assessing SRC within road cycling.
Empowerment for people with dementia (PWD) is not well defined within the research literature and we feel that this is an important area for development. It is important to seek, consult, and co-produce such a definition with PWD who are more actively involved in their communities post diagnosis (e.g. no longer the 'long goodbye'). This study seeks to combine academic literature review methods with participatory/co-production methods in order to address this gap. We feel this approach also adds to developing methodologies in the field of co-production and user involvement.
Cancer is one of the leading cause of death of women worldwide, and breast, ovarian, endometrial and cervical cancers contribute significantly to this every year. Developing early genetic-based diagnostic tools may be an effective approach to increase the chances of survival and provide more treatment opportunities. However, the current cancer genetic studies are mainly conducted independently and, hence lack of common driver genes involved in cancers in women. To explore the potential common molecular mechanism, we integrated four comprehensive literature-based databases to explore the shared implicated genetic effects. Using a total of 460 endometrial, 2,068 ovarian, 2,308 breast and 537 cervical cancer-implicated genes, we identified 52 genes which are common in all four types of cancers in women. Furthermore, we defined their potential functional role in endogenous hormonal regulation pathways within the context of four cancers in women. For example, these genes are strongly associated with hormonal stimulation, which may facilitate rapid diagnosis and treatment management decision making. Additional mutational analyses on combined the cancer genome atlas datasets consisting of 5,919 gynaecological and breast tumor samples were conducted to identify the frequently mutated genes across cancer types. For those common implicated genes for hormonal stimulants, we found that three quarter of 5,919 samples had genomic alteration with the highest frequency in MYC (22%), followed by NDRG1 (19%), ERBB2 (14%), PTEN (13%), PTGS2 (13%) and CDH1 (11%). We also identified 38 hormone related genes, eight of which are associated with the ovulation cycle. Further systems biology approach of the shared genes identified 20 novel genes, of which 12 were involved in the hormone regulation in these four cancers in women. Identification of common driver genes for hormone stimulation provided an unique angle of involving the potential of the hormone stimulants-related genes for cancer diagnosis and prognosis.
Small heat shock proteins (sHSPs) are probably the most diverse in structure and function among the various super-families of stress proteins, and they play essential roles in various biological processes. The sweet potato whitefly, Bemisia tabaci (Gennadius), feeds in the phloem, transmits several plant viruses, and is an important pest on cotton, vegetables and ornamentals. In this research, we isolated and characterized three α-crystallin/sHSP family genes (Bthsp19.5, Bthsp19.2, and Bthsp21.3) from Bemisia tabaci. The three cDNAs encoded proteins of 171, 169, and 189 amino acids with calculated molecular weights of 19.5, 19.2, and 21.3 kDa and isoelectric points of 6.1, 6.2, and 6.0, respectively. The deduced amino acid sequences of the three genes showed strong similarity to sHSPs identified in Hemiptera and Thysanoptera insects species. All three sHSPs genes from Bemisia tabaci lacked introns. Quantitative real-time PCR analyses revealed that the three BtsHSPs genes were significantly up-regulated in Bemisia tabaci adults and pupae during high temperature stress (39, 41, 43, and 45 °C) but not in response to cold temperature stress (-6, -8, -10, and -12 °C). The expression levels of Bthsp19.2 and Bthsp21.3 in pupae was higher than adults in response to heat stress, while the expression level of Bthsp19.5 in adults was higher than pupae. In conclusion, this research results show that the sHSP genes of Bemisia tabaci had shown differential expression changes under thermal stress.
This study evaluates the reproductive toxicity of ethyl acetate and butanolic fractions from crude methanolic leaf extract of Ocimum gratissimum in male Wistar rats. Acute toxicity was assessed to determine the safety dose, Sub-chronic reproductive toxicity studies were carried out by administering daily 25, 100 and 400 mg/kg body weight doses of the fractions to respective group of animals and 1 ml of normal saline daily for the control group for 28 days. Blood, epididymis and testes were harvested for reproductive hormones, sperm parameters, and histopathologic analysis respectively. There was significant (P < 0.05) increase in serum levels of testosterone, body-weight gain, sperm count. There was also apparent increase in mean-testicular weight and preservation of testicular histology with increase spermatogenesis in both the ethyl acetate and butanolic fraction treated groups compared with control. Serum levels of luteinising hormone was however significantly (P < 0.05) decrease across the groups compared to control. These effects were more pronounced in the butanolic fraction group compared to the ethyl acetate treated group. Sperm motility was also significantly (P < 0.05) higher in the ethyl acetate treated group compared to control. Findings from this studies demonstrate that these fractions were non-toxic at the tested doses with regards to male reproduction but, rather, exhibited fertility enhancing effects which was better with the butanolic fraction. Our findings also shows that the ethyl acetate fraction may be safer than the butanolic fraction.
The histopathology department of Usmanu Danfodiyo University Teaching Hospital in Sokoto, Nigeria, conducted a total of 1435 fine needle aspiration biopsies from 1 January 2011 to 31 December 2015, constituting 30% of cytology specimens received. The most common site for the procedure was the breast (655 cases, 45.6%), and 893 cases (63.3%) were neoplastic lesions. Even in resource-poor settings, this underutilised procedure is useful for patient management.
The angiotensin-converting enzyme inhibitors (ACEIs) could improve the symptoms of diabetic nephropathy. Whether the calcium channel blockers (CCBs) could be as effective as ACEIs on treating diabetic nephropathy is controversial. Here, we aimed to compare the efficacy of ACEIs with CCBs on the treatment of diabetic nephropathy by performing a meta-analysis of randomized controlled trials (RCTs).
Specific common and rare single nucleotide variants (SNVs) increase the likelihood of developing sporadic idiopathic pulmonary fibrosis (IPF). We performed target-enriched sequencing on three loci previously identified by a genome-wide association study to gain a deeper understanding of the full spectrum of IPF genetic risk and performed a two-stage case-control association study.
The incidence of primary spontaneous pneumothorax is partly unknown. Commonly quoted estimates were published decades ago and recent large-scale epidemiological publications lack validation. We validated the pneumothorax diagnosis in a national registry and estimated the incidence of primary spontaneous pneumothorax in young patients.
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