Byrdshea2767

Adenosine deaminase acting on RNA 3 (ADAR3) was known as a prognosis factor in gliomas, while its function on neuropathic pain (NP) is barely investigated. Therefore, our present study concentrated on the potential role of ADAR3 in NP.

The chronic constriction injury (CCI) mouse model was established to induce NP in vivo. Behavioral experiments were carried out to analyze mechanical allodynia and thermal hyperalgesia. RT-qPCR and western blotting assays were used to detect the mRNA and protein expressions. The ADAR3-overexpressed adenovirus was injected into the CCI mice through an intrathecal catheter. ELISA was used to detect the contents of IL (interleukin)-6, IL-10, TNF (tumor necrosis factor)-α, IL-1β and IL-18. NLR Family Pyrin Domain Containing 3 (NLRP3) was predicted to be the target gene of ADAR3 using Starbase. The interaction between ADAR3 and NLRP3 was verified via RNA pull-down, RNA immunoprecipitation and Pearson's correlation coefficient assays. Immunohistochemical staining assay visualized the expressions of NLRP3 and caspase1.

Allodynia and hyperalgesia were exacerbated in the CCI mice, which implied a successful establishment of the NP model, while ADAR3 expression level was suppressed. After injecting ADAR3-overexpressed adenovirus into the CCI mice, allodynia, hyperalgesia and inflammation were all restrained. Moreover, NLRP3 was verified to negatively correlated with ADAR3. Additionally, the pyroptosis-related protein NLRP3, ASC, caspase1, IL-1β, IL-18 and GSDMD expressions were all decreased by ADAR3.

In conclusion, ADAR3 alleviated inflammation and pyroptosis of NP through targeting NLRP3, which suggested a therapeutical target for NP.

In conclusion, ADAR3 alleviated inflammation and pyroptosis of NP through targeting NLRP3, which suggested a therapeutical target for NP.Ethylene is an important regulatory phytohormone for sex differentiation and flower development. As the rate-limiting enzyme encoding genes in ethylene biosynthesis, ACS gene family has been well studied in cucumber; however, little is known in other cucurbit crops, such as melon and watermelon, which show diverse sex types in the field. Here, we identified and characterized eight ACS genes each in the genomes of melon and watermelon. According to the conserved serine residues at C-terminal, all the ACS genes could be characterized into three groups, which were supported by the exon-intron organizations and conserved motif distributions. ACS genes displayed diverse tissue-specific expression patterns among four melon and three watermelon sex types. Furthermore, a comparative expression analysis in the shoot apex identified orthologous pairs with potential functions in sex determination, e.g., ACS1s and ACS6s. All ACS orthologs in melon and watermelon exhibited similar expression patterns in monoecious and gynoecious genotypes, except for ACS11s and ACS12s. As expected, the majority of ACS genes were responsive to exogenous ethephon; however, some orthologs exhibited opposite expression patterns, such as ACS1s, ACS9s, and ACS10s. Collectively, our findings provide valuable ACS candidates related to flower development in various sex types of melon and watermelon.

Late radiation toxicity is a major dose-limiting factor in curative cancer radiation therapy. Previous studies identified several risk factors for late radiation toxicity, including both dose-volume factors and genetic predisposition. Herein, we investigated the contribution of genetic predisposition, particularly compared with dose-volume factors, to the risk of late radiation toxicity in patients treated with highly conformal radiation therapy.

We included 179 patients with prostate cancer who underwent treatment with curative external beam radiation therapy between 2009 and 2013. Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.0. compound library chemical Transcriptional responsiveness of homologous recombination repair genes and γ-H2AX foci decay ratios (FDRs) were determined in ex vivo irradiated lymphocytes in a previous analysis. Dose-volume parameters were retrieved by delineating the organs at risk (OARs) on CT planning images. Associations between risk factors and grade ≥2 urts suggest that impaired DNA double-strand break repair in lymphocytes, as quantified by γ-H2AX FDR, is the most critical determining factor of late radiation toxicity. The limited influence of dose-volume parameters could be due to the use of increasingly conformal techniques, leading to improved dose-volume parameters of the organs at risk.

Heart dose and heart disease increase risk for RT-associated cardiac toxicity. We hypothesized that CT coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease.

We analyzed the cumulative incidence of cardiac events in patients with Stage III non-small-cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CT's using MIM (130 HU threshold). Calcifications were defined "None," "Low," and "High," with median volume dividing Low and High.

Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) post-RT. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CT's, 64 (59%) had coronary calcifications with median volume 0.2 cc (range 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3/45), 29% (9/31), and 42% (14/33) of patients with No, Low, and High calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (Low vs. None HR 5.0, p=0.015, High vs. None HR 8.1, p<0.001) and multivariate analyses (Low vs. None HR 7.0, p=0.005, High vs. None HR 10.6, p<0.001, heart mean dose HR 1.1/Gy, p<0.001). Four-year competing risk-adjusted event rates for No, Low, and High calcifications were 4%, 23%, and 34%, respectively.

Coronary calcifications can be considered a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians prior to potentially cardiotoxic cancer treatments.

Coronary calcifications can be considered a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians prior to potentially cardiotoxic cancer treatments.

To test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer.

In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m

weekly), followed by brachytherapy. The phase II component non-randomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT vs. IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association betweenment group.

PET-BMS-IMRT significantly reduced acute grade ≥ 3 neutropenia, but not treatment-related lymphopenia, compared to standard IMRT. We found no evidence that PET-BMS-IMRT impacted chemotherapy delivery or long-term outcomes, and weak evidence of an association between pre-treatment ALC and OS.

PET-BMS-IMRT significantly reduced acute grade ≥ 3 neutropenia, but not treatment-related lymphopenia, compared to standard IMRT. We found no evidence that PET-BMS-IMRT impacted chemotherapy delivery or long-term outcomes, and weak evidence of an association between pre-treatment ALC and OS.Wound is defined as any injury to the body such as damage to the epidermis of the skin and disturbance to its normal anatomy and function. Since ancient times, the importance of wound healing has been recognized, and many efforts have been made to develop novel wound dressings made of the best material for rapid and effective wound healing. Medicinal plants play a great role in the wound healing process. In recent decades, many studies have focused on the development of novel wound dressings that incorporate medicinal plant extracts or their purified active compounds, which are potential alternatives to conventional wound dressings. Several studies have also investigated the mechanism of action of various herbal medicines in wound healing process. This paper attempts to highlight and review the mechanistic perspective of wound healing mediated by plant-based natural products. The findings showed that herbal medicines act through multiple mechanisms and are involved in various stages of wound healing. Some herbal medicines increase the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) which play important role in stimulation of re-epithelialization, angiogenesis, formation of granulation tissue, and collagen fiber deposition. Some other wound dressing containing herbal medicines act as inhibitor of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) protein expression thereby inducing antioxidant and anti-inflammatory properties in various phases of the wound healing process. Besides the growing public interest in traditional and alternative medicine, the use of herbal medicine and natural products for wound healing has many advantages over conventional medicines, including greater effectiveness due to diverse mechanisms of action, antibacterial activity, and safety in long-term wound dressing usage.The ontogeny programs are highly conserved across all vertebrates, although there are significant temporal variations in interspecies developmental processes. Changing the timing and rate of developmental processes could affect subsequent organogenesis profoundly and may also have been critical factors in evolutionary diversity. However, despite their potential importance, the cellular and molecular mechanisms that control interspecies differences in developmental timescale remain unclear. This review highlights recent advances in the experimental models to compare interspecies differences in neurodevelopmental processes, neurogenesis, and neuronal maturation and discusses the possible mechanisms that could generate species-specific timescales.The natural product Huperzine A isolated from Huperzia serrata is a targeted inhibitor of acetylcholinesterase that has been approved for clinical use in the treatment of Alzheimer's disease. Given the large demand for natural sources of Huperzine A, efforts have been made to explore whether Huperzine A (Hup. A) is also produced by endophytic fungi from H. serrata and, if so, identify its biosynthetic pathway. These studies have indicated that endophytic fungi from H. serrata represent a huge and largely untapped resource for natural products (including Hup. A) with chemical structures that have been optimized by evolution for biological and ecological relevance. To date, more than three hundred endophytic fungi have been isolated from H. serrata, of which 9 strains can produce Hup. A, whilst more than 20 strains produce other important metabolites, such as polyketones, xanthones, alkaloids, steroids, triterpenoids, furanone derivatives, tremulane sesquitepenes and diterpenoids. In total, 200 secondary metabolites have been characterized in endophytic fungi from H.