Regression of ovarian cancer xenografts by depleting or inhibiting RLIP.

Ovarian cancer (OC) is the most prevalent and deadly cancer of the female reproductive system. Women will continue to be impacted by OC-related morbidity and mortality. Despite the fact that chemotherapy with cisplatin is the main component as the first-line anticancer treatment for OC, chemoresistance and unfavorable side effects are important obstacles to effective treatment. Targets for effective cancer therapy are required for cancer cells but not for non-malignant cells because they are expressed differently in cancer cells compared to normal cells. Targets for cancer therapy should preferably be components that already exist in biochemical and signalling frameworks and that significantly contribute to the development of cancer or regulate the response to therapy. RLIP is an important mercapturic acid pathway transporter that is crucial for survival and therapy resistance in cancers, therefore, we examined the role of RLIP in regulating essential signalling proteins involved in relaying the inputs from upstream survival pathways and mechanisms contributing to chemo-radiotherapy resistance in OC. The findings of our research offer insight into a novel anticancer effect of RLIP depletion/inhibition on OC and might open up new therapeutic avenues for OC therapy.

Synthesis of a Cd-MOF Fluorescence Sensor and Its Detection of Fe3+, Fluazinam, TNP, and Sulfasalazine Enteric-Coated Tablets in Aqueous Solution.

A Cd-based metal-organic framework (Cd-MOF), named after {[Cd(ttc)(H2O)]·H2O}n (ttc = 1-imidazole-1-yl-2,4,6-benzene-tricarboxylic acid), was synthesized using the solvothermal reaction. The single-crystal structure was determined by single X-ray diffraction analysis, and crystalline characteristics and composition were confirmed by powder X-ray diffraction (PXRD) and thermogravimetric analysis (TG), respectively. Structural analysis showed that the Cd2+ ion is in the seven-coordinated mode, in which ttc2- ion adopts the µ4-η1-η1-η2-η2 coordination mode. It is worth noting that the Cd2+ ion is connected to ttc2- to form a 2D network, and the adjacent 2D network is expanded into a 3D supramolecular network structure through weak hydrogen bonds. The fluorescence sensing experiments indicated that Cd-MOF could not only be used as a fluorescence sensor for Fe3+, fluazinam (FLU), and 2,4,6-trinitrophenolol (TNP) but also for sulfasalazine detection in aqueous solution. To verify the sensitivity of the fluorescent probe, we calculated its detection limit: 5.34 × 10-8 M (Fe3+), 7.8 × 10-8 M (FLU), 1.21 × 10-7 M (TNP), and 2.67 × 10-7 M (SECT). In addition, the quenching mechanism was thoroughly studied.

MOFs-based Fe@YAU-101/GCE electrochemical sensor platform for highly selective detecting trace multiplex heavy metal ions.

The construction of sensors with specific recognition functions can easily, sensitively and efficiently detect heavy metal ions, which is a demand in the field of electrochemical sensing and an important topic in the detection of environmental pollutants. An electrochemical sensor based on MOFs composites was developed for sensing of multiplex metal ions. The large surface area, adjustable porosities and channels in MOFs facilitate successful loading of sufficient quantities highly active units. The active units and pore structures of MOFs are regulated and synergetic with each other to enhance the electrochemical activity of MOFs composites. Thus, the selectivity, sensitivity and reproducibility of MOFs composites have been improved. Fortunately, after characterization, Fe@YAU-101/GCE sensor with strong signal was successfully constructed. In the presence of target metal ions in solution, the Fe@YAU-101/GCE can efficiently and synchronously identify Hg2+, Pb2+, and Cd2+. The detection limits (LOD) are 6.67 × 10-10 M(Cd2+), 3.33 × 10-10 M(Pb2+) and 1.33 × 10-8 M (Hg2+), and are superior to the permissible limits set by the National Environmental Protection Agency. The electrochemical sensor is simple without sophisticated instrumentation and testing processes, hence promising for practical applications.

A Scoring System to Select the Candidates for Adjuvant Chemotherapy Alone in High-Risk Early-Stage Cervical Cancer Patients With Pelvic Lymph Node Metastases After Surgery.

BACKGROUND: The aim was to build a risk scoring system to guide the adjuvant treatment for early-stage cervical cancer patients with pelvic lymph node (LN) metastases after surgery. METHODS: A cohort of 1213 early-stage cervical cancer patients with pelvic LN metastases (T1-2aN1M0) were selected from the NCI SEER database, of which 1040 patients received adjuvant external beam radiotherapy concurrent with chemotherapy (EBRT+Chemo) and 173 patients received adjuvant chemotherapy alone. The Cox regression analysis was applied to identify the risk factors associated with worse survival. The exp (ß) of each independent risk factors from multivariate analysis was assigned to develop the risk scoring system. The total cohort was divided into different risk subgroups accordingly and the efficacy of different adjuvant modalities in each risk subgroups was compared. RESULTS: The patients were divided into 3 risk subgroups (Low-risk: total score <7.20, Middle-risk:7.20≤ total score≤ 8.40, High-risk: total score<8.40) based on the scoring system incorporating 5 independent risk factors. The survival analysis suggested that low-risk (hazard ratio [HR]=1.046, 95% CI: 0.586-1.867; P= 0.879) and middle-risk patients (HR=0.709, 95% CI: 0.459-1.096; P =0.122) could not benefit more from EBRT+Chemo than Chemo alone. However, EBRT+Chemo remained the superiority to Chemo alone in the high-risk subgroup (HR=0.482, 95% CI: 0.294-0.791; P =0.003). CONCLUSION: A risk scoring system has been built to direct the adjuvant treatment for early-stage cervical cancer patients with pelvic LN metastases after surgery, where Chemo alone was totally enough for low-risk and middle-risk patients stratified by the model while EBRT+Chemo was still recommended for patients in the high-risk subgroup.

Postoperative Pain Management Outcomes at a Chinese Hospital: A Cross-Sectional Survey.

PURPOSE: Postoperative pain is one of the most common postoperative complications, and improper management not only adds to patient suffering but also affects patients' recovery. In this study, we measured patients' postoperative pain to understand the status of patients after surgery and to identify factors influencing postoperative pain. DESIGN: A descriptive and cross-sectional study METHODS: This survey was conducted at a large tertiary hospital in Chengdu, Sichuan Province. A total of 655 postoperative inpatients were included. The survey was conducted using the Chinese version of the Houston Pain Outcome Instrument. General patient data, pain management-related factors, and the pain management index were used to survey risk factors. We used t-tests and ANOVA for univariate analysis of each pain outcome category to explore the association with the predictor variables. Then, those variables with a significance level of 0.05 on univariate analysis were entered into multivariable regression analysis to identify parsimonious subsets of independent risk factors. FINDINGS: In this survey, 58.7% of patients experienced moderate to severe pain in the 24-hour postoperative period, and 33.6% of patients had moderate to severe average pain over the 24-hour postoperative period. The postoperative pain impact scores on patient mood, somatic function, patient satisfaction with postoperative pain management, and pain education were 3.5 ± 2.1, 4.3 ± 3.1, 8.9 ± 1.4 and 8.2 ± 1.8, respectively. The pain management index, surgery type, insurance, and pain assessment of nurse were influential factors of postoperative pain intensity. Age, ethnicity, insurance, surgery type, patents' knowledge of pain, and pain assessment of the nurse affected the patients' postoperative physiological function (F = 3.822, R2 = 0.065, P = .000). In addition, area of residence and physician attitudes affected the outcomes of patient satisfaction with pain management (F = 26.652, R2 = 0.259, P = .000). CONCLUSIONS: The incidence of moderate to severe pain in post-surgical patients remains high, and postoperative pain affects patients physically and psychologically. Special attention should be given to patients with lower income and literacy levels.

Water-Stable Cd-MOF with fluorescent sensing of Tetracycline, Pyrimethanil, abamectin benzoate and construction of logic gate.

Due to the indiscriminate abuse of pesticides and antibiotics has caused serious threats to the environment and human and animal bodies, the detection of antibiotics and pesticides has attracted widespread attention in recent years. Herein, a novel 2D Cd (II)-MOF, [Cd(L)0.5(1,2-bimb)] (Cd-L-1,2-bimb), [H4L = 1, 1'-ethylbiphenyl -3, 3', 5, 5'- tetracarboxylic acid, 1, 2-bimb = 1, 2-bis[(1H-imidazol-1-yl) methyl] benzene] is synthesized. Cd-L-1,2-bimb has excellent stability in different organic solvents and in the range of pH 1.1-12.5. Cd-L-1,2-bimb exhibits high selectivity, high sensitivity, and fast luminescent response to pesticides [pyrimethanil (PTH, LOD = 2.2 µM) and abamectin benzoate (AMB, LOD = 2.39 µM)] and antibiotic contaminants tetracycline (TET, LOD = 0.13 µM). Cd-L-1,2-bimb displays discriminative fluorescence when detecting AMB and PTH, and is an implication logic gate. Finally, the possible detection mechanism of Cd-L-1,2-bimb toward different pollutants is also further investigated. This MOF-based multifunctional sensor opens up new prospects for environmental monitors.

A population-based risk scoring system to individualize adjuvant treatment for stage IIIC endometrial cancer patients after surgery.

BACKGROUND: To develop a risk scoring system to tailor the adjuvant treatment for stage IIIC EC patients after surgery. METHODS: Data source was from the Surveillance, Epidemiology, and End Results (SEER) registry, where 3251 post-operative stage IIIC EC patients with different adjuvant treatment were included. Cox regression analysis was used to identify risk factors. The exp (ß) of each independent risk factors generating from the cox analysis was used to construct the risk scoring system, which was further utilized to divide the patients into different risk subgroups and the efficacy of different adjuvant modalities in each risk subgroups would be compared accordingly. RESULTS: Six independent risk factors were identified to develop the scoring system, which further divided the patients into three risk subgroups based on the total risk score (Low-risk≤8.46, 8.47 ≤ Middle-risk≤9.94, High-risk≥9.95). This study revealed that CRT was not superior to RT alone (HR:1.208, 95%CI: 0.852-1.741; P = 0.289) or CT alone (HR:1.260, 95%CI: 0.750-2.116; P = 0.382) in Low-risk subgroup. We also observed that CRT had a survival advantage over other treatment modalities in the Middle-risk subgroup (All P < 0.001), but CRT and CT alone to be superimposable in the High-risk subgroup (HR: 1.395, 95%CI: 0.878-2.216; P = 0.159). CONCLUSION: A risk scoring system has been developed to tailor the adjuvant treatment for stage IIIC EC patients after surgery, where RT or CT alone could be a substitute for CRT in Low-risk patients and CT alone was a potential alternative for High-risk patients while CRT remained to be the optimal choice for the Middle-risk patients.

Translation and validation of M.D. Anderson Symptom Inventory-Thyroid Cancer module in Chinese thyroid cancer patients: a cross-sectional and methodological study.

AIM: To translate and validate the Chinese version of the MDASI-THY among thyroid cancer patients. BACKGROUND: The M.D. Anderson Symptom Inventory-Thyroid Cancer module (MDASI-THY) is one of well-validated instruments for thyroid-specific symptom assessment. To date, the instrument has not been used in China. METHODS: After standard forward- and back-translation procedures, two instruments, the Chinese version of MDASI-THY and the European Organization for Research and Treatment of Cancer QLQ C30, were answered by 309 thyroid patients. The content, convergent discriminant validity and reliability of the MDASI-THY were evaluated. RESULTS: The scale of content validity index (S-CVI) and the item of content validity index (I-CVI) of the instrument were over 0.80. There were significant relationships between MDASI-THY and EORTC QLQ-C30 (r range, 0.139 ~ 0.766, -0.759 ~ -0.461, p < 0.001). Symptoms were severer for patients underwent surgical treatment (Z = -9.999, p < 0.001). The Cronbach's alpha was 0.966 (between 0.954 and 0.827 for subscales). Most symptom items had moderate to high interitem correlations (r range, 0.297 ~ 0.773). CONCLUSIONS: The Chinese version of MDASI-THY demonstrated favorable validity and reliability. It can be used in development of symptom management program in thyroid cancer patients in China. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers can apply this instrument to assess Chinese thyroid cancer patients to increase the understanding of their symptom experience, resulting in a better symptom management.

OsLHY is involved in regulating flowering through the Hd1- and Ehd1- mediated pathways in rice (Oryza sativa L.).

Flowering time (or heading date in crops) is a critical agronomic trait for rice reproduction and adaptation. The circadian clock is an endogenous oscillator that is involved in controlling photoperiodic flowering. The rice LATE ELONGATED HYPOCOTYL (OsLHY), the core oscillator component of circadian clock, is a homolog of the LHY/CCA1 in Arabidopsis. Here we showed that CRISPR/Cas9-engineered mutations in OsLHY caused late flowering in rice only under natural long-day (nLD) and short-day (nSD) conditions, but not artificial SD (10 h light/14 h dark) conditions. In the oslhy mutant, the diurnal expression of circadian clock-related genes was seriously affected under both LD and SD conditions. Furthermore, the expression of the flowering activators Ehd1, Hd3a and RFT1 was down-regulated and flowering repressors Hd1 and Ghd7 was up-regulated in the oslhy mutant under LD conditions. While the transcripts of flowering-related genes were not dramatically influenced under SD conditions. Dual-luciferase assays showed that OsLHY repressed the transcription of OsGI, Hd1, Ghd7, Hd3a, RFT1 and OsELF3, and activated the transcription of Ehd1. Moreover, the yeast one hybrid assay and electrophoretic mobility shift assay confirmed that OsLHY directly repressed OsGI, RFT1 and OsELF3 by binding to their promoters, which is consistent with that in Arabidopsis. These results suggested that the OsLHY can promote rice flowering mainly through regulating Hd1 and Ehd1.

Highly selective detecting Aspartic acid, detecting Ornidazole and information encryption and decryption supported by a heterometallic anionic Cd (II)-K (I)-MOF.

A highly stable heterometallic MOF, {[(Me2NH2)2]·[Cd2K2(L)2(H2O)]}n (H4L = terphenyl-2, 2', 4, 4'-tetracarboxylic acid) (1), was synthesized. 1 featuring one-dimensional channels can efficiently detect Aspartic acid with a low limit of detection (LOD) value (2.5 µM). More interestingly, 1 can encapsulate Eu3+ and sensitize the visible-emitting characteristic fluorescence of Eu3+ in aqueous solution. Then, Eu3+@CdK-MOF is found to be an excellent fluorescence sensor for the detection of Ornidazole (ODZ) and the portable ODZ test paper is also successfully designed. Eu3+@CdK-MOF can also be used as fluorescent ink to write some words. The words can be hidden when treated with acid vapor and then the words can be restored when treated with alkaline vapor. More importantly, the hidden information can be read repeatedly. Therefore, this reversible light-emitting and reusable property have great potential for development in information encryption and decryption and information storage.

Information encryption, highly sensitive detection of nitrobenzene, tetracycline based on a stable luminescent Cd-MOF.

A stable luminescent Cd-MOF, formulated as [Cd(L)0.5(4, 4'-bpy)0.5]·H2O (1), (H4L = 1, 1'-ethylbiphenyl -3, 3', 5, 5'- tetracarboxylic acid, 4, 4' -bpy = 4, 4'-bipyridine), is acquired under solvothermal conditions. 1 exhibits stability in the pH range from 1.5 to 12.2 and in different organic solvents. 1 can detect tetracycline and nitrobenzene by fluorescence quenching with high sensitivity and selectivity. The detection limits are 0.14 µM and 14 nM, respectively. Interestingly, 1 can encapsulate Tb3+ and sensitize its characteristic peaks. Moreover, the fluorescent ink is prepared by using the luminescent properties of the Tb3+@Cd-MOF. The light of the fluorescent ink disappears in an acid gas HCl atmosphere and then reappears in an alkaline gas ammonia atmosphere. This phenomenon can be repeated and the reason for this phenomenon is also explained in the article. Therefore, Tb3+@Cd-MOF has huge application potential in information encryption.

Ibrutinib ameliorates cerebral ischemia/reperfusion injury through autophagy activation and PI3K/Akt/mTOR signaling pathway in diabetic mice.

Bruton's tyrosine kinase (BTK) is involved in the diabetogenic process and cerebral ischemic injury. However, it remained unclear whether BTK inhibition has remedial effects on ischemia/reperfusion (I/R) injury complicated with diabetes. We aim to investigate the regulatory role and potential mechanism of ibrutinib, a selective inhibitor of BTK, in cerebral I/R injured diabetic mice. The cytotoxicity and cell vitality tests were performed to evaluate the toxic and protective effects of ibrutinib at different incubating concentrations on normal PC12 cells or which were exposed to high glucose for 24 h, followed by hypoxia and reoxygenation (H/R), respectively. Streptozotocin (STZ) stimulation-induced diabetic mice were subjected to 1 h ischemia and then reperfusion. Then the diabetic mice received different dosages of ibrutinib or vehicle immediately and 24 h after the middle cerebral artery occlusion (MCAO). The behavioral, histopathological, and molecular biological tests were then performed to demonstrate the neuroprotective effects and mechanism in I/R injured diabetic mice. Consequently, Ibrutinib improved the decreased cell viability and attenuated oxidative stress in the high glucose incubated PC12 cells which subjected to H/R injury. In the I/R injured diabetic mice, ibrutinib reduced the cerebral infarct volume, improved neurological deficits, ameliorated pathological changes, and improved autophagy in a slightly dose-dependent manner. Furthermore, the expression of PI3K/AKT/mTOR pathway-related proteins were significantly upregulated by ibrutinib treatment. In summary, our finding collectively demonstrated that Ibrutinib could effectively ameliorate cerebral ischemia/reperfusion injury via ameliorating inflammatory response, oxidative stress, and improving autophagy through PI3K/Akt/mTOR signaling pathway in diabetic mice.

Extensively Current Activity of Transposable Elements in Natural Rice Accessions Revealed by Singleton Insertions.

Active transposable elements (TEs) have drawn more attention as they continue to create new insertions and contribute to genetic diversity of the genome. However, only a few have been discovered in rice up to now, and their activities are mostly induced by artificial treatments (e.g., tissue culture, hybridization etc.) rather than under normal growth conditions. To systematically survey the current activity of TEs in natural rice accessions and identify rice accessions carrying highly active TEs, the transposon insertion polymorphisms (TIPs) profile was used to identify singleton insertions, which were unique to a single accession and represented the new insertion of TEs in the genome. As a result, 10,924 high-confidence singletons from 251 TE families were obtained, covering all investigated TE types. The number of singletons varied substantially among different superfamilies/families, perhaps reflecting distinct current activity. Particularly, eight TE families maintained potentially higher activity in 3,000 natural rice accessions. Sixty percent of rice accessions were detected to contain singletons, indicating the extensive activity of TEs in natural rice accessions. Thirty-five TE families exhibited potentially high activity in at least one rice accession, and the majority of them showed variable activity among different rice groups/subgroups. These naturally active TEs would be ideal candidates for elucidating the molecular mechanisms underlying the transposition and activation of TEs, as well as investigating the interactions between TEs and the host genome.

Targeting CA-125 Transcription by Development of a Conditionally Replicative Adenovirus for Ovarian Cancer Treatment.

CA-125, encoded by the MUC16 gene, is highly expressed in most ovarian cancer cells and thus serves as a tumor marker for monitoring disease progression or treatment response in ovarian cancer patients. However, targeting MUC16/CA-125 for ovarian cancer treatment has not been successful to date. In the current study, we performed multiple steps of high-fidelity PCR and obtained a 5 kb DNA fragment upstream of the human MUC16 gene. Reporter assays indicate that this DNA fragment possesses transactivation activity in CA-125-high cancer cells, but not in CA-125-low cancer cells, indicating that the DNA fragment contains the transactivation region that controls specific expression of the MUC16 gene in ovarian cancer cells. We further refined the promoter and found a 1040 bp fragment with similar transcriptional activity and specificity. We used this refined MUC16 promoter to replace the E1A promoter in the adenovirus type 5 genome DNA, where E1A is an essential gene for adenovirus replication. We then generated a conditionally replicative oncolytic adenovirus (CRAd) that replicates in and lyses CA-125-high cancer cells, but not CA-125-low or -negative cancer cells. In vivo studies showed that intraperitoneal virus injection prolonged the survival of NSG mice inoculated intraperitoneally (ip) with selected ovarian cancer cell lines. Furthermore, the CRAd replicates in and lyses primary ovarian cancer cells, but not normal cells, collected from ovarian cancer patients. Collectively, these data indicate that targeting MUC16 transactivation utilizing CRAd is a feasible approach for ovarian cancer treatment that warrants further investigation.

Natural variation and evolutionary dynamics of transposable elements in Brassica oleracea based on next-generation sequencing data.

Brassica oleracea comprises various economically important vegetables and presents extremely diverse morphological variations. They provide a rich source of nutrition for human health and have been used as a model system for studying polyploidization. Transposable elements (TEs) account for nearly 40% of the B. oleracea genome and contribute greatly to genetic diversity and genome evolution. Although the proliferation of TEs has led to a large expansion of the B. oleracea genome, little is known about the population dynamics and evolutionary activity of TEs. A comprehensive mobilome profile of 45,737 TE loci was obtained from resequencing data from 121 diverse accessions across nine B. oleracea morphotypes. Approximately 70% (32,195) of the loci showed insertion polymorphisms between or within morphotypes. In particular, up to 1221 loci were differentially fixed among morphotypes. Further analysis revealed that the distribution of the population frequency of TE loci was highly variable across different TE superfamilies and families, implying a diverse expansion history during host genome evolution. These findings provide better insight into the evolutionary dynamics and genetic diversity of B. oleracea genomes and will potentially serve as a valuable resource for molecular markers and association studies between TE-based genomic variations and morphotype-specific phenotypic differentiation.

Repositioning Quinacrine Toward Treatment of Ovarian Cancer by Rational Combination With TRAIL.

Quinacrine has been identified as a potent DR5-inducing agent that sensitizes cancer cells to TRAIL-induced apoptosis. In the current study, we found that quinacrine increased DR5 mRNA levels significantly in ovarian cancer cell lines regardless of p53 status. Further study showed the half-life of DR5 in quinacrine-treated cells was significantly prolonged, indicating that DR5 protein degradation was inhibited by quinacrine. We tested if the combination of TRAIL and quinacrine could be effective in ovarian cancer treatment in vitro and in ovarian cancer xenograft mouse models. We found that quinacrine enhanced TRAIL sensitivity or reversed TRAIL resistance in all the ovarian cancer cell lines tested. Mice treated with quinacrine and TRAIL remained disease-free for up to 20 weeks, however, mice treated with TRAIL or quinacrine alone and in control group died within ~8 weeks after treatment. Intraperitoneal delivery of quinacrine and TRAIL is rational and practical with extraordinary synergistic anti-cancer effects in preclinical models of ovarian cancer. Clinical investigation of combining quinacrine with TRAIL for ovarian cancer treatment is warranted.

Anthocyanin Protects Cardiac Function and Cardiac Fibroblasts From High-Glucose Induced Inflammation and Myocardial Fibrosis by Inhibiting IL-17.

Diabetic cardiomyopathy (DCM) is one of the major causes of death in diabetic patients. Its pathogenesis involves inflammation and fibrosis that damages the heart tissue and impairs cardiac function. Interleukin (IL)-17, a pro-inflammatory cytokine that plays an important role in a variety of chronic inflammatory processes can serve as an attractive therapeutic target. Anthocyanin, a water-soluble natural pigment, possesses impressive anti-inflammatory activity. However, its role in DCM is unclear. Hence, we investigated the protective effect of anthocyanin on the cardiovascular complications of diabetes using a mouse type 1 diabetes mellitus model induced by streptozotocin. Cardiac function and structural alterations in diabetic mice were tested by echocardiography, hematoxylin and eosin staining, and Masson trichrome staining. Immunohistochemistry was performed to evaluate the distribution and deposition of IL-17 and collagen I and III from the left ventricular tissues of diabetic mice. Cell viability was measured using the methyl thiazolyl tetrazolium assay. Protein levels of IL-17, tumor necrosis factor α, IL-1ß, and IL-6 were determined using enzyme-linked immunosorbent assay. IL-17 and collagen I and III were detected by western blotting and immunofluorescence, and their mRNA levels were quantified using quantitative reverse transcription PCR. We observed that anthocyanin lowered blood glucose, improved cardiac function, and alleviated inflammation and fibrosis in the heart tissue of diabetic mice. Meanwhile, anthocyanin reduced the expression of IL-17 in high-glucose-treated cardiac fibroblasts and exhibited an anti-inflammatory effect. Deposition of collagen I and III was also decreased by anthocyanin, suggesting that anthocyanin contributes to alleviating myocardial fibrosis. In summary, anthocyanin could protect cardiac function and inhibit IL-17-related inflammation and fibrosis, which indicates its therapeutic potential in the treatment of diabetes mellitus-related complications.

Delayed diagnosis of prosopagnosia following a hemorrhagic stroke in an elderly man: A case report.

BACKGROUND: Acquired prosopagnosia is a rare condition characterized by the loss of familiarity with previously known faces and the inability to recognize new ones. It usually occurs after the onset of brain lesions such as in a stroke. The initial identification of prosopagnosia generally relies on a patient's self-report, which can be challenging if it lacks an associated chief complaint. There were few cases of prosopagnosia presenting purely as eye symptoms in the previous literature confirmed by functional magnetic resonance imaging (MRI). CASE SUMMARY: We present a case of delayed diagnosis of prosopagnosia after a right hemisphere stroke in an elderly man whose chief complaint was persistent and progressive "blurred vision" without facial recognition impairment. Ophthalmic tests revealed a homonymous left upper quadrantanopia, with normal visual acuity. He was found by accident to barely recognize familiar faces. The patient showed severe deficit in face recognition and perception tests, and mild memory loss in neuropsychological assessments. Further functional MRI revealed the visual recognition deficits were face-specific. After behavioral intervention, the patient started to rely on other cues to compensate for poor facial recognition. His prosopagnosia showed no obvious improvement eight months after the stroke, which had negative impact on his social network. CONCLUSION: Our case demonstrates that the presentation of prosopagnosia can be atypical, and visual difficulties might be a clinical manifestation solely of prosopagnosia, which emphasizes the importance of routinely considering face recognition impairment among elderly patients with brain lesions.

MiR-135b protects cardiomyocytes from infarction through restraining the NLRP3/caspase-1/IL-1ß pathway.

BACKGROUND: Myocardial infarction (MI) is the most common cause of cardiovascular morbidity and mortality worldwide. Despite the identification of many pathogenic genes associated with MI, the underlying molecular mechanisms remain poorly understood. MicroRNAs (miRNAs, miRs), which regulate target genes at the post-transcriptional level, play a significant role in the regulation of cardiovascular diseases such as MI. Pyroptosis is a caspase-1-dependent pro-inflammatory programmed cell death (PCD) mechanism. The role of pyroptosis in several diseases associated with various miRNAs has been studied extensively. Meanwhile, the role of NOD-like receptor-containing pyrin 3 (NLRP3)/caspase-1/interleukin-1ß (IL-1ß) pathway in cardiac diseases has also been more recognized. METHODS: We established a mice MI model which ligated with the left anterior descending coronary artery and a cardiomyocytes injury model treated by hydrogen peroxide (H2O2) to detect the expressions of miR-135b and NLRP3/caspase-1/IL-1ß pathway. Then miR-135b mimic, agomir-135b, and α-MHC-miR-135b transgenic mice were used to evaluate the effects of miR-135b overexpression. RESULT: We demonstrated that miR-135b was downregulated after cardiomyocytes injury both in vivo and in vitro. Pyroptosis pathway was also activated. MiR-135b overexpression remarkably restored impaired cardiac function and attenuated the upregulation of NLRP3/caspase-1/IL-1ß pathway. CONCLUSIONS: The present findings shed light on the protective role of miR-135b in MI mediated by the inhibition of the NLRP3/caspase-1/IL-1ß pathway.

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting α v integrin/FAK/Src signaling in oral squamous cell carcinoma cells.

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), αv integrin is a crucial mediator of multicellular clustering and collective movement in vitro; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent in vitro. Firstly, we found marked enrichment of αv integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of αv integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed αv integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro. Overall, these results suggest that PEP06 polypeptide 30 inhibiting αv integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.