LINC00511 promotes melanoma progression by targeting miR-610/NUCB2.

Long intergenic noncoding RNA 00511 (LINC00511) predicts poor prognosis in various malignancies and functions as an oncogene in distinct malignant tumors. The role of LINC00511 in melanoma progression was assessed. In our research, expression of LINC00511 in melanoma cells was detected by quantitative reverse transcription PCR. Colony formation and CCK8 assays were used to detect cell proliferation. Cell metastasis was evaluated by transwell and wound healing assays. Downstream target of LINC00511 was investigated by luciferase activity assay. As a results, LINC00511 was elevated in melanoma cells and tissues. Loss of LINC00511 decreased cell viability, reduced proliferation, invasion, and migration of melanoma. miR-610 was target of LINC00511, and miR-610 binds to 3'UTR of nucleobindin-2 (NUCB2). Inhibition of miR-610 attenuated LINC00511 deficiency-induced decrease of NUCB2 in melanoma cells. Loss of miR-610 weakened LINC00511 deficiency-induced decrease of cell viability, proliferation, invasion, and migration of melanoma. In conclusion, silence of LINC00511 reduced cell proliferation and metastasis of melanoma through down-regulation of miR-610-mediated NUCB2.

Low-dose topiramate and hydrochlorothiazide-associated early acute myopia and angle narrowing: A case report.

Purpose: To report a unique case of topiramate and hydrochlorothiazide associated with acute myopia and angle narrowing. Patients and methods: A 34-year-old Asian woman presented with prominent binocular visual acuity decrease 6 h after taking only one dose of 25 mg topiramate, 25 mg hydrochlorothiazide, and 22.4 mg fluoxetine to lose weight. She was subsequently diagnosed with acute bilateral myopia and angle narrowing and was started on topical therapy. Results: Initial examination revealed a decreased visual acuity of 20/100 bilaterally, an elevated intraocular pressure of 23 mmHg in the right eye and 24 mmHg in the left eye, suprachoroidal effusions, and angle narrowing. After the discontinuation of these drugs and the use of IOP-lowering medication, the patient made full recovery. Conclusion: We speculate that there is a drug-drug interaction between topiramate and hydrochlorothiazide that may lead to the angle narrowing in a short time and at a low dose. Timely discontinuation of the drug usually leads to complete recovery within days to weeks.

miRNA-633 and KAI1 as Potential Biomarkers of Malignant Melanoma with Gastric Cancer.

OBJECTIVE: Malignant melanoma with gastric cancer is one of the most malignant tumors. However, there have been no reports on the effects of KAI1 and miRNA-633 on the survival and prognosis of patients with malignant melanoma with gastric cancer. METHODS: Fifty patients with malignant melanoma and gastric cancer were collected from October 2017 to December 2019. The clinical parameters included clinical information, such as sex, age, tumor size, and tumor staging. RT-qPCR was used to detect the expression of KAI1 and miRNA- 633. The role of KAI1 and miRNA-633 on the overall survival of melanoma was explored by the Pearson chi-square test, Spearman-rho correlation test, Univariate and multivariate cox regression analyses, and Kaplan-Meier method. Furthermore, the bioinformatic analysis was used to verify the role of KAI1 and miRNA-633 on malignant melanoma with gastric cancer. RESULTS: The expression of KAI1 and miRNA-633 was significantly related with the tumor size and staging of tumor (p<0.05) based on the Pearson chi-square test. Spearman's correlation coefficient displayed that KAI1 was significantly correlated with the miRNA-633 (ρ=-0.439, p=0.001). The result of multivariate cox proportional regression analysis showed that KAI1 (HR =0.109, 95% CI: 0.031-0.375, p< 0.001), and miRNA-633 (HR = 13.315, 95% CI: 3.844-46.119, p<0.001) were significantly associated with overall survival. CONCLUSION: The low expression level of KAI1 and high expression of miRNA-633 are significantly correlated with the poor overall survival prognosis of malignant melanoma with gastric cancer, to provide a basis for KAI1 and miRNA-633 to become novel molecular targets for malignant melanoma with gastric cancer.

Degradation of tetracycline by activating persulfate using biochar-based CuFe2O4 composite.

Biochar derived from Lentinus edodes (LBC) and CuFe2O4 (CuFe2O4@LBC) composites were prepared by the hydrothermal method, and were applied to activate persulfate (PDS) for degrading tetracycline (TC) in a wide pH range. The CuFe2O4@LBC composites were characterized by XRD, FTIR, SEM, and XPS. LBC-derived biochars greatly reduced the aggregation of CuFe2O4 particles and enhanced the catalytic performance of CuFe2O4. CuFe2O4@LBC catalyst could remove 85% of tetracycline within 100 min under visible light. In addition, the removal rate of TC reached 76% after five cycles, indicating that the composite had good stability and reusability. Simple classical quenching experiments suggested that the degradation of TC could be mainly attributed to •OH and •S [Formula: see text].

Clinical Treatment Study of Secondary Multiple Squamous Cell Carcinoma with Psoriasis Vulgaris.

Dermatologic diseases are the fourth most frequent nonfatal common illness, yet they have a psychological, economical, and professional burden that is comparable to or larger than other chronic conditions. From a survey in China of 6 provinces, the overall prevalence of psoriasis with squamous cell carcinoma was 0.47%. According to the current investigation, the outburst of skin disease was not associated with gender, but mainly with the climate of the environment; that is, dry cold weather will more likely to induce psoriasis. Approximately 3% of people around the world have psoriasis, which is near the most common autoimmune skin disease in adults. By simple estimation, there are at least two hundred million psoriasis patients in the world. Therefore, it is not just a simple health problem in a country or a region but a serious global challenge. Of note, about half of the adult patients had been reported to be sick in their childhood and they mostly fell ill around 10 years old. Actinic keratosis is perhaps the most common, followed by squamous cell carcinoma and, to a lesser extent, acne vulgaris, psoriasis, and hidradenitis suppurativa, as well as dermatitis herpetiformis. 5-Fluorouracil (5-FU) 0.5 percent is used topically to treat actinic keratosis and squamous cell carcinoma with good outcomes, while it might cause significant toxicity in certain patients. Dapsone, a Valosin-containing protein, is a medication that is often used to treat inflammatory skin disorders like psoriatic arthritis, but it can occasionally cause hemolytic anemia. Furthermore, biologic medications for the treatment of moderate-to-severe psoriasis and multiple squamous cell carcinoma have proven to be successful and safe; nevertheless, a small percentage of patients do not react to biologic treatment in the long term or do not respond at all. Based on the data from the China Food and Drug Administration, the majority of chemical drugs are utilized as the topical formulations, while Chinese medicines are mainly delivered by an oral route, suggesting that the market for topical preparations of Chinese medicine to treat skin diseases like psoriasis is worth exploration. This large interindividual diversity in response could be caused by changes in genes that encode proteins implicated in the disease's pathologic environment or the medication's mechanism of action. Pharmacogenetics is the study of the association between genetic differences and medication response, which is valuable for identifying nonresponsive patients and those who are more likely to suffer toxicity as a result of treatment. This study highlights the pharmacogenetic recommendations for dermatology therapies that have the strongest evidence at this time, highlighting those that have been incorporated in clinical practice guides. Pharmacogenetic clinical guidelines for multiple squamous cell carcinoma and psoriasis vulgaris were found in this investigation. Here, for multiple squamous cell carcinoma trichohyalin-like 1 (TCHHL1), 5-fluorouracil (5-FU) 0.5% is recommended. Along with that dapsone, Valosin-containing protein can be recommended for treating the psoriasis vulgaris. We made some clinical trials over the two diseases, and from the result obtained, we hypothesize that the suggested drug may be a novel therapeutic target in treating the multiple squamous cell carcinoma with psoriasis vulgaris.

Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018.

BACKGROUND: An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported. METHODS: To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed. RESULTS: Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q → H) and 670th (E390: N → S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China. CONCLUSIONS: The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.

Prognostic and clinicopathological significance of the platelet-to-lymphocyte ratio in melanoma: A meta-analysis involving 2099 patients.

To investigate the prognostic role of the platelet-to-lymphocyte ratio (PLR) in melanoma through a meta-analytical method. The literature was searched using the PubMed, Embase, Web of Science, Cochrane Library, and Scopus electronic platforms. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and their corresponding 95% confidence intervals (CIs) were calculated. Begg's test and Egger's test were used to assess potential publication bias. A total of eight retrospective cohort studies involving 2099 patients were included in the meta-analysis. No significant association between the PLR and OS was found (HR = 1.39; 95% CI = 0.97-1.99; P = .075). There was also a nonsignificant correlation between the PLR and PFS (HR = 1.49; 95% CI = 0.98-2.27; P = .065). In addition, there was no significant association between the PLR and sex (odds ratio [OR] = 1.14; 95% CI = 0.23-5.66; P = .869) or age (OR = 0.81; 95% CI = 0.41-1.59; P = .539). No significant publication bias was found in this meta-analysis. The pooled analysis suggests that the PLR may not be a significant prognostic marker in patients with melanoma.

D-Pinitol Ameliorates Imiquimod-Induced PsoriasisLike Skin Inflammation in a Mouse Model via the NF-κB Pathway.

Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.

Silencing of HAS2-AS1 mediates PI3K/AKT signaling pathway to inhibit cell proliferation, migration, and invasion in glioma.

Hyaluronan synthase 2 (HAS2)-AS1 (natural antisense transcript of HAS2) functions as oncogenic long noncoding RNA (lncRNA) in oral squamous cell carcinoma, breast cancer, and osteosarcoma. The role of HAS2-AS1 in glioma remains unknown. In our research, HAS2-AS1 expression was elevated in glioma tissues compared with normal brain tissues. Moreover, high levels of HAS2-AS1 expression was observed in patients with glioma with high WHO grade (III-IV) or large tumor size ( > 4 cm). The survival analysis from The Cancer Genome Atlas showed glioma cases with high HAS2-AS1 expression that had shorter disease-free survival time and overall survival time than those with low HAS2-AS1 expression. In vitro studies suggested that knocking down HAS2-AS1 expression inhibited glioma cell viability, migration, and invasion through phosphoinositide 3-kinase/protein kinase B signaling pathway. In conclusion, HAS2-AS1 may be considered as a predictor for clinical outcome and a potential therapeutic target in glioma.

MicroRNA-610 inhibits tumor growth of melanoma by targeting LRP6.

Accumulating evidence showed that aberrant miRNAs expression was involved in initiation and progression of melanoma. However, the investigation of different miRNAs in melanoma remain attractive. In this research, we demonstrated that miR-610 expression was decreased in melanoma tissues and cell lines. The clinical data showed that the reduced miR-610 expression was obviously associated with adverse prognostic characteristics. Furthermore, our results suggested that miR-610 had a function of prognostic indicator for 5-year predicted-survival of melanoma patients. The ectopic overexpression of miR-610 suppressed cell proliferation, cell cycle progression and promoted apoptosis while miR-610 knockdown reversed the effect in vitro and in vivo. Additionally, miR-610 could modulate LRP6 by directly interacting to its 3'-UTR. In clinical samples of melanoma, miR-610 inversely correlated with LRP6. The biological function of miR-610 on melanoma cells was abrogated by alternation of LRP6 expression. In summary, our research indexed that miR-610 had a function of tumor suppressor in regulating the proliferation, cell cycle and apoptosis of melanoma via targeting LRP6. Hence, it may represent a novel potential therapeutic target and prognostic marker for melanoma.

Zerumbone inhibits melanoma cell proliferation and migration by altering mitochondrial functions.

It has been reported that zerumbone (ZER) has marked effects on the regulation of cell proliferation and migration in multiple types of cancer, and has anti-cancer effects on various types of malignant cell. However, the effects and underlying molecular mechanisms of treatment with ZER on melanoma cells remain unclear. In the present study, the effect of treatment with ZER on the proliferation, migration and mitochondrial function of the human melanoma cell line CHL-1 was investigated. The results of the present study indicated that treatment with ZER significantly inhibited CHL-1 cell proliferation (P<0.001). Cell migration analysis further demonstrated that ZER inhibited the migration of CHL-1 cells (P<0.001). Treatment with ZER significantly increased cellular reactive oxygen species levels (P<0.001), reduced matrix membrane potential (P<0.001), decreased ATP (P<0.001) and mitochondrial DNA (P<0.001) levels, and decreased mitochondrial transcription factor A mRNA levels (P=0.002). The results of the present study suggested that the inhibition of proliferation and migration was mediated by altered mitochondrial function. In conclusion, the results of the present study suggested that ZER has chemotherapeutic effects on human melanoma cells by altering mitochondrial function.

Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression in Non-Small Cell Lung Cancer.

Previous studies reported that elevated expression of long noncoding RNA (lncRNA) GAS5 led to the arrest of non-small cell lung cancer (NSCLC) cell growth and a promotion of apoptosis both in vitro and in vivo. However, its underlying molecular mechanism in NSCLC is still unclear. In the present study, we noted that GAS5 was downregulated in NSCLC tissues and cells and was negatively correlated with miR-23a expression. Luciferase reporter assay and qRT-PCR analysis demonstrated that GAS5 directly interacted with miR-23a and reversely regulated its expression. miR-23a overexpression markedly promoted NSCLC cell proliferation and invasion, while GAS5 overexpression dramatically inhibited NSCLC cell proliferation and invasion and promoted apoptosis. Functional analysis indicated that miR-23a overexpression significantly abolished GAS5 overexpression-induced inhibition of proliferation and invasion, as well as promotion of apoptosis in NSCLC cells. Moreover, xenograft experiments further revealed that upregulation of GAS5 notably impaired the growth of transplanted tumors by suppressing miR-23a in nude mice. These results suggested that overexpression of lncRNA GAS5 inhibits tumorigenesis of NSCLC by inhibiting miR-23a in vitro and in vivo, providing a potential therapeutic strategy for patients with NSCLC.

MicroRNA138 regulates keratin 17 protein expression to affect HaCaT cell proliferation and apoptosis by targeting hTERT in psoriasis vulgaris.

The purpose of this study is to explore the how microRNA-138 (miR-138) affects the expression of keratin 17 (K17) and psoriasis development. Twenty-eight skin lesions from patients with psoriasis vulgaris and twenty-four normal skin tissues from healthy controls were collected. The HaCaT cells were assigned into blank, negative control (NC), miR-138 mimic, miR-138 inhibitor, hTERT siRNA and miR-138 inhibitor+hTERT siRNA groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the miR-138 expression. The hTERT and K17 protein expression were testified by Western Blotting. MTT assay, flow cytometry with PI single staining and Annexin V/PI double staining were performed to detect the cell proliferation activity, cell cycle and apoptosis, respectively. Compared with the healthy skin, the expression of miR-138 decreased in the psoriatic skin, but hTERT and K17 protein expressions increased. The miR-138 mimic and hTERT siRNA groups showed significantly decreased hTERT and K17 protein expressions, inhibited cell proliferation, increased number of cells at G1 phase and elevated apoptosis rate in comparison to the rest three groups. The hTERT and K17 protein expressions in the miR-138 inhibitor group were up-regulated with promoted cell proliferation and reduced apoptosis rate as compared with the other four groups. In the miR-138 inhibitor+hTERT siRNA group, the hTERT and K17 protein expressions, cell proliferation and apoptosis were intermediate between the miR-138 inhibitor and hTERT siRNA groups. These findings indicated that the expression of miR-138 was lower in the psoriatic skin, which was negatively correlated to K17 expression. MiR-138 may regulate K17 protein expression to affect HaCaT cell proliferation and apoptosis by targeting hTERT gene.

Updated meta-analysis on HER2 polymorphisms and risk of breast cancer: evidence from 32 studies.

BACKGROUND: Several studies have been performed to investigate the association of the HER2 Ile655Val polymorphism and breast cancer risk. However, the results were inconsistent. To understand the precise relationship, a meta-analysis was here conducted. MATERIALS AND METHODS: A search of PubMed conducted to investigate links between the HER2 Ile655Val polymorphism and breast cancer, identified a total of 32 studies, of which 29, including 14,926 cases and 15,768 controls, with odds ratios (ORs) with 95% confidence intervals were used to assess any association. RESULTS: In the overall analysis, the HER2 Ile655Val polymorphism was associated with breast cancer in an additive genetic model (OR=1.136, 95% CI 1.043-1.239, p=0.004) and in a dominant genetic (OR=1.118, 95% CI 1.020-1.227, p=0.018), while no association was found in a recessive genetic model. On subgroup analysis, an association with breast cancer was noted in the additive genetic model (OR=1.111, 95% CI: 1.004-1.230, p=0.042) for the Caucasian subgroup. No significant associations were observed in Asians and Africans in any of the genetic models. CONCLUSIONS: In summary, our meta-analysis findings suggest that the HER2 Ile655Val polymorphism is marginally associated with breast cancer susceptibility in worldwide populations with additive and dominant models, but not a recessive model.

Feasibility study on repair for cranial defect of immaturity.

AIM: To evaluate use of a titanium mesh to fill cranial defects in growing animals, as a model for juvenile humans. MATERIAL AND METHODS: Thirty two-month-old Seghers pigs were evenly assigned to one of three groups: controls, a defect group (unrepaired 5 x 5 cm lesion), and a repair group (repaired 5 x 5 cm lesions). Histological evaluations and morphological measurements were conducted to compare the groups. RESULTS: Two pigs in the defect group died. New bone formation was evident in the cranial lesions of pigs in the defect and repair groups. There were no differences in histological observations (p = 0.081), brain weight (p = 0.063), or indexed brain circumference measurements (p = 0.066) between the groups. CONCLUSION: Closure of cranial defects with a titanium mesh did not limit growth of the cranium or cause abnormal central nervous system development. While there was new bone growth in the cranial defects, the bone was not sufficiently strong to withstand external trauma.