Mosquitoes pose a major threat to human health as they spread many deadly diseases like malaria, dengue, chikungunya, filariasis, Japanese encephalitis and Zika. Identification and use of novel molecular tools are essential to combat the spread of vector borne diseases. Genome editing tools have been used for the precise alterations of the gene of interest for producing the desirable trait in mosquitoes. Deletion of functional genes or insertion of toxic genes in vector mosquitoes will produce either knock-out or knock-in mutants that will check the spread of vector-borne diseases. Presently, three types of genome editing tools viz., zinc finger nuclease (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (Cas9) are widely used for the editing of the genomes of diverse organisms. These tools are also applied in vector mosquitoes to control the spread of vector-borne diseases. A few studies have been carried out on genome editing to control the diseases spread by vector mosquitoes and more studies need to be performed with the utilization of more recently invented tools like CRISPR/Cas9 to combat the spread of deadly diseases by vector mosquitoes. The high specificity and flexibility of CRISPR/Cas9 system may offer possibilities for novel genome editing for the control of important diseases spread by vector mosquitoes. In this review, we present the current status of genome editing research on vector mosquitoes and also discuss the future applications of vector mosquito genome editing to control the spread of vectorborne diseases.
Over the past few decades, researchers have paid considerable attention to the relationship between estrogen and bone metabolism. Nevertheless, few studies have examined the potential role of chemokines in estrogen regulation of bone metabolism. Chemokines are members of a superfamily of low-molecular-weight chemoattractant cytokines. Various chemokines and their corresponding transmembrane G protein-coupled receptors play distinct roles in the functional regulation and homeostasis of the immune and skeletal systems. This review summarizes the evidence that chemokines and estrogen display cooperative behavior in the skeletal system, with a focus on the mechanisms by which estrogen regulates the chemotactic factors that affect bone metabolism. Chemokines appear to represent a novel area for further examination in order to develop new therapeutics to treat disorders of bone metabolism.
Anemia is one of the most important complications of HIV infection. In China, the prevalence, risk factors, and association between anemia and prognosis in HIV-infected patients are poorly elucidated. We analyzed data from 3452 HIV-infected patients not yet on combined antiretroviral therapy (cART) attending Beijing Ditan Hospital from June, 2003 to December, 2015. The overall prevalence of anemia was 9.8% (7.6% mild, 1.9% moderate, and 0.2% severe anemia). Female sex (odds ratio [OR] = 3.71, 95% confidence interval [CI]: 1.46-6.51, p = 0.003), age 40-59 years (OR = 2.54, 95% CI: 1.59-4.05, p < 0.001), body mass index < 18.5 kg/m2 (OR = 2.23, 95% CI: 1.31-3.79, p = 0.003), baseline HIV RNA CI: 1.32-5.99, p = 0.007) were risk factors for anemia. Age 40-59 years (adjusted hazard ratio [AHR] = 5.76, 95% CI: 1.62-20.55, p = 0.007), and anemia ‒ mild (AHR = 7.46, 95% CI: 1.48-37.50, p = 0.015), moderate (AHR = 9.89, CI: 1.35-72.38, p = 0.024), and severe (AHR = 28.29, 95% CI: 2.75-290.54, p = 0.005) anemia ‒ were associated with an increased hazard of death. In this cohort, mild anemia was most common. Anemia was associated with female sex, older age, lower body mass index, lower baseline CD4 count, and higher viral load. Moreover, anemia was associated with an increased risk of death. These findings should promote awareness among physicians to make a timely diagnosis of HIV and to help physicians prioritize prevention and intervention strategies for anemia in HIV-infected patients.
Skin senescence is induced by various factors including intrinsic aging and extrinsic aging. The current study compared the expression of microRNAs in young facial skin and senescent facial skin, and this study identified skin aging-related microRNAs. According to the results from a microRNA PCR Array, miR-124 was the microRNA that increased the most in senescent skin compared to young skin. Real-time PCR with a greater number of samples indicated that the increase in miR-124 levels in senescent facial skin was statistically significant. In situ hybridization was performed, and results indicated that the signal for miR-124 was evident in keratinocytes of senescent skin but not in those of young skin. The morphology of cultured normal human epidermal keratinocytes (NHEKs) transfected with a miR-124 mimic changed to an enlarged and irregular shape. In addition, the number of NHEKs positive for senescence-associated β-galactosidase (SA-β-gal) increased significantly as a result of the overexpression of the miR-124 mimic. The expression of miR-124 increased in UVB-irradiated NHEKs compared to controls in a dose-dependent manner. Expression of miR-124 in A431, a human cutaneous squamous cell carcinoma (SCC) cell line, decreased significantly compared to that in NHEKs. Forced overexpression of miR-124 as a result of the transfection of a miR-124 mimic in A431 resulted in the significant suppression of the proportion of cancer cells. The current results indicated that miR-124 increases as a result of cell senescence and that it decreases during tumorigenesis. The effect of supplementation of miR-124 in an SCC cell line suggests that senescence induction therapy with microRNA may be a new therapeutic approach for treatment of SCC.
Spinal cord injuries (SCIs) can induce primary and secondary injury, resulting in severe neurological damage and dysfunction in patients. Studies have reported that signal transducer and activator of transcription 3 (STAT3) plays an important role in the inflammatory immune response and neural stem cell differentiation. In order to examine whether a STAT3 inhibitor can prevent worsening of an SCI and promote neural stem cell differentiation, a rat model of surgically induced SCI was created and rats were treated with the STAT3 inhibitor S31-201. Tissue from the injured region was harvested and fixed in formalin and paraffin. H&E staining was used to look for morphological changes. The Basso, Beattie, and Bresnahan locomotor scale (BBB score), somatosensory evoked potentials (SEP), and motor evoked potentials (MEP) were examined. Western blotting was used to detect the expression of β-tubulin ш, vimentin, GFAP, NF-200, and OX-42 protein. Results indicated that the STAT3 inhibitor S31-201 reduces the extent of SCI and it promotes neural stem cell differentiation.
The fruit of Evodia rutaecarpa (Juss.) Benth has been used widely in traditional medicine therapy. Although it has been shown to possess many pharmacological activities, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated. In the present study, we investigated the pro-apoptotic effects of an ethanol extract isolated from immature fruits of E. rutaecarpa (EEER) in HeLa human cervical cancer cells. EEER treatment decreased the cell viability of HeLa cells in a concentration-dependent manner, which was related to apoptotic cell death resulting from apoptotic body formation, DNA fragmentation, and an increased population of annexin V+-positive cells. EEER treatment significantly suppressed anti-apoptotic Bcl-2 expression, leading to subsequent loss of mitochondrial membrane potential (MMP), while it did not change expression levels of death receptor (DR)-related proteins. EEER treatment increased activity of caspase-3 and -9 but not caspase-8, and pretreatment of a caspase-3 inhibitor markedly attenuated EEER-induced apoptosis. Furthermore, EEER activated the AMP-activated protein kinase (AMPK) signaling pathway; however, inhibition of AMPK markedly abrogated EEER-induced apoptosis. Overall, the results suggest that the apoptotic activity of EEER may be associated with a caspase-dependent cascade through activation of the intrinsic signaling pathway connected with AMPK activation. E. rutaecarpa could be a prospective clinical application to treat human cervical cancer.
Human DNA is the main unit that shapes human characteristics and features such as behavior. Thus, it is expected that changes in DNA (DNA mutation) influence human characteristics and features. Face is one of the human features which is unique and also dependent on his gen. In this paper, for the first time we analyze the variations of human DNA and face simultaneously. We do this job by analyzing the fractal dimension of DNA walk and face during human aging. The results of this study show the human DNA and face get more complex by aging. These complexities are mapped on fractal exponents of DNA walk and human face. The method discussed in this paper can be further developed in order to investigate the direct influence of DNA mutation on the face variations during aging, and accordingly making a model between human face fractality and the complexity of DNA walk.
Previous studies demonstrated that miR-15a-5p was probably associated with human hepatocellular carcinoma, while the function of miR-15a-5p in OA (Osteoarthritis) still remains unknown. Here, we uncovered the potential role of miR-15a-5p on OA pathogenesis and confirmed its predicted target VEGFA (Vascular Endothelial Growth Factor A). Measured by RT-PCR, miR-15a-5p expression increased remarkably while VEGFA expression was significantly decreased in OA chondrocytes compared with normal conditions. According to Luciferase activity assay, miR-15a-5p directly targeted the 3'-UTR of VEGFA to inhibit its expression. Functional analysis including CCK-8 assay and flow cytometry revealed that overexpression of VEGFA or inhibition of miR-15a-5p promoted cell proliferation, suppressed cell apoptosis and reduced matrix degradation in OA chondrocytes. Moreover, rescue assays carried out with both expression of VEGFA and miR-15a-5p demonstrated that miR-15a-5p contributes to cell apoptosis and matrix degradation via inhibiting VEGFA. We further provided evidence that multiple proteins related to matrix synthesis were regulated by miR-15a-5p and VEGFA using Western blot and ELISA assays. Taken together, our findings elucidated an underlying mechanism by which miR-15a-5p regulates viability and matrix degradation of OA and indicated a new target for OA diagnosis and therapy.
Recent evidence suggests that the endoplasmic reticulum stress (ERS)-thioredoxin-interacting protein (TXNIP)-inflammation chain contributes to diabetic renal injury. The aim of the current study was to investigate whether total glucosides of peony (TGP) could inhibit ERS and attenuate up-regulation of TXNIP in the kidneys of rats with streptozotocin-induced diabetes. TGP was orally administered daily at a dose of 50, 100, or 200 mg/kg for 8 weeks. The expression of glucose-regulated protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (p-PERK), phosphor- eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), and TXNIP was assessed. Results indicated that TGP significantly decreased diabetes-induced albuminuria and it acted by down-regulating activation of the ERS-TXNIP-inflammation chain in the kidneys of diabetic rats. These findings indicate that renoprotection from TGP in diabetic rats possibly contributed to inhibition of ERS and decreased expression of TXNIP. These findings also offer a new perspective from which to study the molecular mechanisms of diabetic nephropathy and prevent its progression.
Management of recurrent hepatitis C following liver transplantation still remains a challenge. Here, we report five patients who achieved viral responses following combined treatment with ledipasvir and sofosbuvir. All the patients received tacrolimus for immunosuppression. No dose adjustment was made before the ledipasvir and sofosbuvir therapy. All completed the intended 12-week treatment course with the full dose of ledipasvir and sofosbuvir. There were no significant adverse events greater than grade 2. During the study period, no acute rejection episodes were detected. The trough levels of tacrolimus were maintained stably. Hepatitis C virus RNA was not detected at week 12 in any of the patients. Based on the findings from this pilot study, combined ledipasvir and sofosbuvir therapy for 12 weeks is effective and safe for living - donor liver transplantation recipients with recurrence of hepatitis C virus.
Retinal pericytes play an important role in the maintenance of retinal microvascular homeostasis. We performed a secretory peptidome of primary human retinal pericytes. Using liquid chromatography-tandem mass spectrometry analysis in the culture medium of retinal pericytes, we identified 256 peptides derived from 114 proteins, and identified a novel partial fragment Leu163-His183 (termed ΔADT) of adrenotensin (ADT). To elucidate the role of ΔADT as a soluble mediator of pericyte-endothelial cell interactions, we investigated the bioactivity of ΔADT in human retinal microvascular endothelial cells (HRMVECs). The cell proliferation assay indicated that the proliferation of HRMVECs was promoted by ADT or ΔADT. Moreover, ΔADT had a greater growth promoting effect than ADT in HRMVECs and induced migration and tube formation of HRMVECs. We also observed actin reorganization and that the levels of phosphorylated focal adhesion kinase in ΔADT stimulated HRMVECs. These results showed that ΔADT induces profound actin reorganization and increases the levels of phosphorylated focal adhesion kinase. Collectively, our study showed that ΔADT has an angiogenic activity, and suggested that ΔADT is a novel angiogenic peptide.
Non-invasive ampullary tumors, may be treated with endoscopic (EA) or surgical ampullectomy (SA). However, evidence on the morbidity of these techniques remains limited. This pilot study aimed to assess and compare morbidity of EA and SA. Patients undergoing EA or SA for non-invasive ampullary tumors were retrospectively analyzed and compared. Outcomes were postoperative complications graded with Clavien Classification and Comprehensive Complication Index (CCI), and length of stay (LoS). A review of the literature was performed to propose an evidence-based algorithm to treat ampullary tumors. A total of 11 EA and 19 SA were identified and analyzed. EA was associated with shorter intervention (51 vs. 191 min, p < 0.001) and decreased blood loss (0 vs. 100 mL, p < 0.001). Postoperative complications were more frequent after surgery compared to endoscopy (9% vs. 68%, p = 0.002). Surgical patients showed a higher CCI (0 vs. 8.7, p < 0.001). LoS was reduced in patients undergoing endoscopy (0 vs. 14 days, p < 0.001), with comparable readmissions rates (p = 0.126). Necessity of subsequent treatment was more frequent after endoscopic, compared to SA (5 vs. 1, p = 0.016). EA was associated with lower morbidity than SA and appeared as an appropriate first-line treatment for non-invasive ampullary tumors. SA remains a valuable alternative after EA failure.