EXPRESSION OF USP22 AND CPC IN ORAL CANCER

Oral cancer is a common cancer of the head and neck. Oral squamous cell carcinoma (OSCC) represents almost 90% of the total cases of head and neck cancer. Ubiquitin‑specific protease 22 (USP22) is a deubiquitinating hydrolase, and it is highly expressed in various types of cancer, which also typically have a poor prognosis. Aurora‑B and Survivin, which belong to the chromosomal passenger complex, are also highly expressed in a number of types of cancer. In the present study, USP22 expression and its associations with Aurora‑B and Survivin, and the clinicopathological features in OSCC were explored. USP22 is highly expressed in OSCC. Overexpression of USP22 is associated with lymph node metastasis and histological grade (P<0.01). Additionally, the expression of USP22 was positively associated with Aurora‑B (P<0.01), Survivin (P<0.01), and Ki‑67 (P<0.01). Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora‑B, Survivin and Cyclin B, together with the upregulation of cyclin‑dependent kinase inhibitor 1A (p21). These data suggest that USP22, Aurora‑B and Survivin promote the OSCC development and may represent novel targets for OSCC diagnosis and treatment in the future

Aurora Kinase Inhibitors in Head and Neck Cancer

Aurora kinases are a group of serine/threonine kinases responsible for the regulation of mitosis. In recent years, with the increase in Aurora kinase-related research, the important role of Aurora kinases in tumorigenesis has been gradually recognized. Aurora kinases have been regarded as a new target for cancer therapy, resulting in the development of Aurora kinase inhibitors. The study and application of these small-molecule inhibitors, especially in combination with chemotherapy drugs, represents a new direction in cancer treatment. This paper reviews studies on Aurora kinases from recent years, including studies of their biological function, their relationship with tumor progression, and their inhibitors

Application of 18F-FDG PET/CT imaging in gallbladder inflammatory pseudotumor with elevated CA199: a case report and review of literature

BackgroundGallbladder inflammatory pseudotumor (GIPT) is a nonspecific chronic proliferative inflammation of the gallbladder. At present, the pathogenesis is not clear, which may be related to bacterial and viral infections, congenital diseases, gallstones, chronic cholangitis and so on. GIPT is rare and the imaging examination has no obvious specificity. There are few reports on the 18F-FDG PET/CT imaging characteristics of GIPT. In this paper, 18F-FDG PET/CT findings of GIPT with elevated CA199 are reported and the literature is reviewed.Case descriptionA 69-year-old female patient presented with recurrent intermittent right upper abdominal pain for more than 1 year, followed by nausea and vomiting for 3 hours, without fever, dizziness, chest tightness and other symptoms. Complete CT, MRI, PET/CT and related laboratory tests, CEA (-), AFP (-), Ca199 224.50U/mL ↑,18F-FDG PET/CT images showed uneven thickening at the bottom of the gallbladder, slightly increased gallbladder volume, eccentric and localized thickening of the gallbladder body wall, nodular soft tissue density shadow, clear boundary, smooth gallbladder wall, presence and smooth hepatobiliary interface, increased FDG radioactivity uptake, SUVmax was 10.2.The tumor was resected after operation and was diagnosed as gallbladder inflammatory pseudotumor by postoperative pathology.Conclusion18F-FDGPET/CT imaging has a certain significance for gallbladder inflammatory pseudotumor. In patients with chronic cholecystitis, when the CA199 increases, the gallbladder wall appears localized thickening, the hepatobiliary interface exists and is smooth, and the 18F-FDG metabolism is mildly to moderately increase. Gallbladder cancer cannot be diagnosed alone, and the possibility of gallbladder inflammatory pseudotumor should also be considered. However, it should be noted that the cases with unclear diagnosis should still be actively treated with surgery, so as not to delay the treatment opportunity

Role of GABAAR in the Transition From Acute to Chronic Pain and the Analgesic Effect of Electroacupuncture on Hyperalgesic Priming Model Rats

Chronic pain is a costly health problem that impairs health-related quality of life when not effectively treated. Regulating the transition from acute to chronic pain is a new therapeutic strategy for chronic pain that presents a major clinical challenge. The underlying mechanisms of pain transition are not entirely understood, and strategies for preventing this transition are lacking. Here, a hyperalgesic priming model was used to study the potential mechanism by which γ-aminobutyric acid receptor type A (GABAAR) in the dorsal root ganglion (DRG) contributes to pain transition. Furthermore, electroacupuncture (EA), a modern method of acupuncture, was administered to regulate pain transition, and the mechanism underlying EA's regulatory effect was investigated. Hyperalgesic priming was induced by intraplanar injection of carrageenan (Car)/prostaglandin E2 (PGE2). The decrease in mechanical withdrawal threshold (MWT) induced by PGE2 returned to baseline 4 h after injection in NS + PGE2 group, and still persisted 24 h after injection in Car + PGE2 group. Lower expression of GABAAR in the lumbar DRG was observed in the model rats. Furthermore, activating or blocking GABAAR could reversed the long-lasting hyperalgesia induced by Car/PGE2 injection or produced a persistent hyperalgesia. In addition, GABAAR may be involved in Protein Kinase C epsilon (PKCε) activation in the DRG, a mark molecular of pain transition. EA considerably increased the mechanical pain thresholds of hyperalgesic priming model mammals in both the acute and chronic phases. Furthermore, EA upregulated the expression of GABAAR and inhibited the activation of PKCε in the DRG. In addition, peripheral administration of picrotoxin blocked the analgesic effect of EA on the model rats and abolished the regulatory effect of EA on PKCε activation. These findings suggested that GABAAR plays a key role in both the transition from acute to chronic pain and the analgesic effect of EA on hyperalgesic priming

PARP6 acts as a tumor suppressor via downregulating Survivin expression in colorectal cancer

Poly (ADP-ribose) polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins and are involved in a variety of biological processes. PARP6 is a novel member, and our previous findings suggest that PARP6 may act as a tumor suppressor via suppressing cell cycle progression. However, it is still unclear that PARP6 function besides growth suppression in colorectal cancer (CRC). In this study, we examined tumor suppressive roles of PAPR6 in CRC cells both in vitro and in vivo. We found that PARP6 inhibited colony formation, invasion and migration as well as cell proliferation. Moreover, ectopic overexpression of PARP6 decreased Survivin expression, which acts as an oncogene and is involved in apoptosis and mitosis. We confirmed the inverse correlation between PARP6 and Survivin expression in CRC cases by immunohistochemistry. Importantly, CRC cases with downregulation of PARP6 and upregulation of Survivin showed poor prognosis. In summary, PARP6 acts as a tumor suppressor via downregulating Survivin expression in CRC. PARP6 can be a novel diagnostic and therapeutic target together with Survivin for CRC

Electroacupuncture Regulates Pain Transition Through Inhibiting PKCε and TRPV1 Expression in Dorsal Root Ganglion

Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4-L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε-TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system

The SUMOylation of Human Cytomegalovirus Capsid Assembly Protein Precursor (UL80.5) Affects Its Interaction with Major Capsid Protein (UL86) and Viral Replication

Human Cytomegalovirus Capsid Assembly Protein Precursor (pAP, UL80.5) plays a key role in capsid assembly by forming an internal protein scaffold with Major Capsid Protein (MCP, UL86) and other capsid subunits. In this study, we revealed UL80.5 as a novel SUMOylated viral protein. We confirmed that UL80.5 interacted with the SUMO E2 ligase UBC9 (58-93aa) and could be covalently modified by SUMO1/SUMO2/SUMO3 proteins. 371Lysine located within a ψKxE consensus motif on UL80.5 carboxy-terminal was the major SUMOylation site. Interestingly, the SUMOylation of UL80.5 restrained its interaction with UL86 but had no effects on translocating UL86 into the nucleus. Furthermore, we showed that the removal of the 371lysine SUMOylation site of UL80.5 inhibited viral replication. In conclusion, our data demonstrates that SUMOylation plays an important role in regulating UL80.5 functions and viral replication

Prime Editing: An All-Rounder for Genome Editing

Prime editing (PE), as a &ldquo;search-and-replace&rdquo; genome editing technology, has shown the attractive potential of versatile genome editing ability, which is, in principle, currently superior to other well-established genome-editing technologies in the all-in-one operation scope. However, essential technological solutions of PE technology, such as the improvement of genome editing efficiency, the inhibition of potential off-targets and intended edits accounting for unexpected side-effects, and the development of effective delivery systems, are necessary to broaden its application. Since the advent of PE, many optimizations have been performed on PE systems to improve their performance, resulting in bright prospects for application in many fields. This review briefly discusses the development of PE technology, including its functional principle, noteworthy barriers restraining its application, current efforts in technical optimization, and its application directions and potential risks. This review may provide a concise and informative insight into the burgeoning field of PE, highlight the exciting prospects for this powerful tool, and provide clues for questions that may propel the field forward

Improving the estimation of canopy cover from UAV-LiDAR data using a pit-free CHM-based method

Accurate and rapid estimation of canopy cover (CC) is crucial for many ecological and environmental models and for forest management. Unmanned aerial vehicle-light detecting and ranging (UAV-LiDAR) systems represent a promising tool for CC estimation due to their high mobility, low cost, and high point density. However, the CC values from UAV-LiDAR point clouds may be underestimated due to the presence of large quantities of within-crown gaps. To alleviate the negative effects of within-crown gaps, we proposed a pit-free CHM-based method for estimating CC, in which a cloth simulation method was used to fill the within-crown gaps. To evaluate the effect of CC values and within-crown gap proportions on the proposed method, the performance of the proposed method was tested on 18 samples with different CC values (40−70%) and 6 samples with different within-crown gap proportions (10−60%). The results showed that the CC accuracy of the proposed method was higher than that of the method without filling within-crown gaps (R2 = 0.99 vs 0.98; RMSE = 1.49% vs 2.2%). The proposed method was insensitive to within-crown gap proportions, although the CC accuracy decreased slightly with the increase in within-crown gap proportions

Exploring the diversity, bioactivity of endophytes, and metabolome in Synsepalum dulcificum

Synsepalum dulcificum exhibits high edible and medicinal value; however, there have been no reports on the exploration of its endophyte resources. Here, we conducted analyses encompassing plant metabolomics, microbial diversity, and the biological activities of endophytic metabolites in S. dulcificum. High-throughput sequencing identified 4,913 endophytic fungal amplicon sequence variants (ASVs) and 1,703 endophytic bacterial ASVs from the roots, stems, leaves, flowers, and fruits of S. dulcificum. Fungi were classified into 5 phyla, 24 classes, 75 orders, 170 families, and 313 genera, while bacteria belonged to 21 phyla, 47 classes, 93 orders, 145 families, and 232 genera. Furthermore, there were significant differences in the composition and content of metabolites in different tissues of S. dulcificum. Spearman’s correlation analysis of the differential metabolites and endophytes revealed that the community composition of the endophytes correlated with plant-rich metabolites. The internal transcribed spacer sequences of 105 isolates were determined, and phylogenetic analyses revealed that these fungi were distributed into three phyla (Ascomycota, Basidiomycota, and Mucoromycota) and 20 genera. Moreover, 16S rDNA sequencing of 46 bacteria revealed they were distributed in 16 genera in three phyla: Actinobacteria, Proteobacteria, and Firmicutes. The antimicrobial activities (filter paper method) and antioxidant activity (DPPH and ABTS assays) of crude extracts obtained from 68 fungal and 20 bacterial strains cultured in different media were evaluated. Additionally, the α-glucosidase inhibitory activity of the fungal extracts was examined. The results showed that 88.6% of the strains exhibited antimicrobial activity, 55.7% exhibited antioxidant activity, and 85% of the fungi exhibited α-glucosidase inhibitory activity. The research suggested that the endophytes of S. dulcificum are highly diverse and have the potential to produce bioactive metabolites, providing abundant species resources for developing antibiotics, antioxidants and hypoglycemic drugs