ROS-mediated ITGB5 promotes tongue squamous cell carcinoma metastasis through epithelial mesenchymal transition and cell adhesion signal pathway.

PURPOSE: Integrin ß5 (ITGB5) is an integrin ß subunit member widely expressed in the human bodies, especially in cancer cells and tissues, which is a key factor in promoting tumor metastasis. In this study we investigated the differential expression of ITGB5 in tongue squamous cell carcinoma (TSCC), especially in those with lymph node metastasis, and revealed the possible mechanism. METHODS: The expression of ITGB5 in TSCC was analyzed by database and verified by immunohistochemistry through 135 TSCC patients' tissue sections from Sun Yat-sen Memorial Hospital and Guangzhou First People's Hospital. The relationship between ITGB5 and lymph node metastasis or prognosis was analyzed retrospectively. The effects of ITGB5 on TSCC cells were examined through knocking down or overexpression and its possible regulator and signal pathway were explored. RESULTS: The expression of ITGB5 in TSCC was higher than that in adjacent tissue, and the expression in patients with lymph node metastasis was higher than that in patients without lymph node metastasis. The high expression of ITGB5 predicted a worse prognosis. Knock down of ITGB5 suppressed invasion and migration of TSCC cells, while overexpression of ITGB5 contributed to invasion and migration. Reactive oxygen species (ROS) regulated epithelial mesenchymal transition (EMT), and we further verified that ROS enhanced the expression of ITGB5 to promote the metastasis of TSCC. Mechanistically, ITGB5 functions through cell adhesion signal pathway. CONCLUSION: The increased expression of ITGB5 in tongue squamous cell carcinoma with lymph node metastasis may be a potential target for evaluating lymph node metastasis and worse prognosis of tongue squamous cell carcinoma. Scavenge of ROS or knock down of ITGB5 may be the strategies to overcome metastasis of TSCC.

Adalimumab induced exacerbation of psoriasis in patients with combined pemphigus: A case report.

RATIONALE: Psoriasis is an immune-related disease caused by genetic factors, abnormalities in the immune system and environmental factors, while pemphigus is an autoimmune disease caused by the autoimmune system attacking the skin and mucosal tissues. Herein, we aimed to report a rare case of adalimumab induced exacerbation of psoriasis patients with pemphigus. The rare disease causes considerable challenges for clinical diagnosis and treatment. PATIENT CONCERNS: The patient was a 43-year-old man with intermittent erythema and scaling all over the body for more than 20 years, and blisters and vesicles on the trunk and limbs for 1 month. Half a year ago, the patient had blisters on the limbs, and was diagnosed with deciduous pemphigus in a hospital, and the blisters subsided after being given traditional Chinese medicine orally. Half a month ago, the erythema area was enlarged, and adalimumab 80 mg intramuscular injection was given for 1 time after consultation in the hospital. On the following day, the area of erythema and scales was suddenly enlarged obviously compared with the previous 1, and obvious blisters and vesicles appeared on the limbs, neck, and trunk, which were aggravated progressively and accompanied by obvious itching and pain. DIAGNOSES: The patient was diagnosed with psoriasis in patients with combined pemphigus. INTERVENTION: After combined treatment with methylprednisolone and cyclosporine, the skin lesions have basically recovered. OUTCOMES: The skin lesions have basically healed. Follow up for 6 months without recurrence. LESSONS: Methylprednisolone combined with cyclosporine may be an option in treating patients with psoriasis patients with pemphigus.

Chemical Comparison and Identification of Xanthine Oxidase Inhibitors of Dioscoreae Hypoglaucae Rhizoma and Dioscoreae Spongiosae Rhizoma by Chemometric Analysis and Spectrum-Effect Relationship.

Dioscoreae hypoglaucae Rhizoma (DH) and Dioscoreae spongiosae Rhizoma (DS) are two similar Chinese herbal medicines derived from the Dioscorea family. DH and DS have been used as medicines in China and other Asian countries for a long time, but study on their phytochemicals and bioactive composition is limited. This present study aimed to compare the chemical compositions of DH and DS, and explore the anti-xanthine oxidase components based on chemometric analysis and spectrum-effect relationship. Firstly, an HPLC method was used to establish the chemical fingerprints of DH and DS samples, and nine common peaks were selected. Then, hierarchical clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were employed to compare and discriminate DH and DS samples based on the fingerprints data, and four steroidal saponins compounds (protodioscin, protogracillin, dioscin, gracillin) could be chemical markers responsible for the differences between DH and DS. Meanwhile, the anti-xanthine oxidase activities of these two herbal medicines were evaluated by xanthine oxidase inhibitory assay in vitro. Pearson correlation analysis and partial least squares regression analysis were subsequently used to investigate the spectrum-effect relationship between chemical fingerprints and xanthine oxidase inhibitory activities. The results showed that four steroidal saponins, including protodioscin, protogracillin, methyl protodioscin and pseudoprogracillin could be potential anti-xanthine oxidase compounds in DH and DS. Furthermore, the xanthine oxidase inhibitory activities of the four selected inhibitors were validated by anti-xanthine oxidase inhibitory assessment and molecular docking experiments. The present work provided evidence for understanding of the chemical differences and the discovery of the anti-xanthine oxidase constituent of DH and DS, which could be useful for quality evaluation and bioactive components screening of these two herbal medicines.

Ultrasonographic classification of 26 cases of fetal umbilical-portal-systemic venous shunts and the correlations with fetal chromosomal abnormalities.

OBJECTIVE: To investigate the ultrasonographic classification of fetal umbilical-portal-systemic venous shunts (UPSVS) and the correlations with fetal chromosomal abnormalities. METHODS: We retrospectively analyzed the ultrasound characteristics and the corresponding chromosomal abnormalities of 26 cases of fetal UPSVS prenatally diagnosed. RESULTS: A total of 26 fetuses diagnosed as UPSVS were included, including four cases of type I UPSVS, ten of type II, three of type IIIA, and nine of type IIIB. Four cases of type I were all complicated by fetal heart enlargement and heart insufficiency, of which one case had multiple malformations, and all four cases terminated pregnancies. Six of ten cases of type II terminated pregnancies, including four of Down's syndrome, one of twin reversed arterial perfusion sequence, one of fetal edema but with normal copy number variation (CNV) by chorionic villus sampling. The other four of ten cases were isolated type II with normal chromosomes, which were delivered at full term and were normal in growth and development when followed up 34 months after birth. Three cases of type IIIA all terminated pregnancies, of which one had multiple malformations, one had right multicystic dysplastic kidney, and one had fetal heart enlargement and heart failure. Among nine of type IIIB, seven with chromosomal abnormalities and/ or complicated malformations terminated pregnancies, and two with isolated type IIIB and normal chromosomes were delivered at full term, and were normal in growth and development (one was followed up to 33 months after birth and the other 20 months after birth). CONCLUSION: Fetal UPSVS can be clearly diagnosed and typed by prenatal ultrasonography. Fetal prognosis is determined by the types of UPSVS and complicated malformations and/ or chromosomal abnormalities. The probability of fetal chromosomal abnormalities in UPSVS fetuses is related to the ultrasonographic classification.

Performance of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Scedosporium, Acremonium-Like, Scopulariopsis, and Microascus Species.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a powerful microorganism identification tool. Research on MALDI-TOF MS identification of rare filamentous fungi is still lacking. This study aimed to evaluate the performance of MALDI-TOF MS in the identification of Scedosporium, Acremonium-like, Scopulariopsis, and Microascus species. Sabouraud broth cultivation and formic acid/acetonitrile protein extraction were used for MALDI-TOF MS identification by a Bruker Biotyper system. An in-house database containing 29 isolates of Scedosporium, Acremonium-like, Scopulariopsis, and Microascus spp. was constructed. A total of 52 clinical isolates were identified using the Bruker Filamentous Fungi Library v1.0 (FFL v1.0) alone, and Filamentous Fungi Library v1.0 plus the in-house library, respectively. The mass spectrum profile (MSP) dendrograms of the 28 Scedosporium isolates, 26 Acremonium-like isolates, and 27 Scopulariopsis and Microascus isolates were constructed by MALDI Biotyper OC 4.0 software, respectively. The correct species identification rate significantly improved when using the combined databases compared with that when using FFL v1.0 alone (Scedosporium spp., 75% versus 0%; Acremonium-like spp., 100% versus 0%; Scopulariopsis and Microascus spp., 100% versus 62.5%). The MSP dendrograms differentiated Acremonium-like species, Scopulariopsis and Microascus species clearly, but cannot distinguish species in the Scedosporium apiospermum complex. In conclusion, with an expanded database, MALDI-TOF MS is an effective tool for the identification of Scedosporium, Acremonium-like, Scopulariopsis, and Microascus species.

[Exploration and practice of blended teaching in "Introduction to Life Sciences" for non-biology students].

In the era of Internet +, teaching models in universities are undergoing changes due to the rapid development of information technology. Blended teaching, combining online with offline teaching, is being implemented and developed in universities. In order to reform teaching mode and improve teaching effect, the curriculum team carried out the exploration of blended teaching reform for the "Introduction to Life Sciences" for non-biology students. The course combined high-level MOOC (Massive Open Online Course), small class teaching, diversified platform and multi-dimensional teaching mode, built a multi-disciplinary collaborative teaching team, formed a multi-dimensional evaluation system focusing on process and ability, practiced the education concept of combining knowledge teaching and value leading, gained valuable practical experience, and achieved the expected teaching results. It can provide reference for the reform and construction of similar courses in other colleges and universities. The development of blended teaching expands the breadth and depth of teaching, stimulates students' interest and potential for learning, opens up students' thinking and perspective, cultivates students' scientific literacy and comprehensive ability, and plays a positive role in the cultivation of innovative and inter-disciplinary talents.

Evaluation and Comparison of Bioactive Constituents of Artemisiae argyi Folium Collected at Different Developmental Stages.

BACKGROUND: Artemisiae argyi Folium (AF) has been used as herbal medicine and a food supplement in China and other Asian countries. There is no report about whether the different developmental stages can influence the bioactive compositions of AF. OBJECTIVE: To investigate the dynamic changes of bioactive constituents of AF collected at different developmental stages. METHOD: The volatile and nonvolatile bioactive components in AF collected at six different developmental stages were analyzed by gas chromatography-mass spectrometry and (GC-MS) high-performance liquid chromatography (HPLC). Chemometrics analysis, including principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA), were further performed to compare and discriminate the AF samples based on the analysis results. RESULTS: The results indicated the bioactive compositions in AF underwent obvious changes during the period of growth. The volatile compositions of AF collected at different stages were the same, while their relative contents were different. Six volatile compounds could be regarded as chemical markers, which were responsible for the intergroup differences. The phenolic profiles of AF at different stages indicated a similar composition when the content levels of the main phenolic compounds were variated. CONCLUSIONS: The comparative results will facilitate better understanding of dynamic changes of bioactive constituents of AF samples collected at different stages and will provide useful information for cultivation and utilization of this herbal medicine. HIGHLIGHTS: The volatile and nonvolatile bioactive components in AF collected at different developmental stages were evaluated and compared for the first time.

The High Diversity and Variable Susceptibility of Clinically Relevant Acremonium-Like Species in China.

Acremonium-like fungi are emerging as important opportunistic pathogens in cutaneous, subcutaneous and serious invasive infections, especially in immunocompromised and debilitated individuals, and Acremonium infections are usually resistant to antifungal therapy. Several molecular studies have demonstrated that many species in the genus Acremonium are polyphyletic, and currently, the genus is restricted to the family Bionectriaceae (Hypocreales). Molecular identification and in vitro antifungal susceptibility tests of Acremonium-like fungi isolated from human clinical specimens in China were performed in this study. Three genetic loci: the large subunit ribosomal RNA gene (LSU), ribosomal internal transcribed spacer and elongation factor 1-α (EF1-α), were used to assess their taxonomic position for correct identification among various species. The multilocus study of twenty-eight strains showed that these strains were distributed in three main lineages: egyptiacum, Cordycipitaceae and Sarocladium; Acremonium egyptiacum and Sarocladium kiliense were the main species of these strains, and three isolates were too phylogenetically distant to be considered undescribed species. Relatively low minimum inhibitory concentrations (MICs) of 0.25-2 and 0.031-0.5 µg/mL were found for voriconazole and terbinafine for most species, respectively. Varied antifungal activities of ciclopirox olamine, amorolfine and posaconazole were found in our study. However, no antifungal effect of sertaconazole, itraconazole or fluconazole was observed against most strains. This is the first study on Acremonium-like species diversity by multilocus sequence analyses and antifungal susceptibility of clinically relevant isolates in China.

Population differentiation and genetic diversity of Trichophyton rubrum as revealed by highly discriminatory microsatellites.

Little is known regarding the population information of Trichophyton rubrum due to a lack of strains with clear sampling information and molecular markers with high discriminatory power. In the present study, we developed a set of microsatellite markers that have a cumulative discriminatory power was 0.993. Using these microsatellites loci, 243 strains T. rubrum that had clear sampling information were analysed. Three genetic diversity indices (Shannon's Information Index, Nei's unbiased gene diversity and allelic richness) were shown to be related to the human population size of the sampling city rather than mean annual temperature or humidity. Population structure analyses revealed that T. rubrum can be separated into two clusters. AMOVA results indicated that genetic variation was more significant between these two clusters than among geographical populations. Our work is the first to reveal population information of T. rubrum using highly discriminatory molecular markers, and suggest that T. rubrum populations in cities with larger population size might have better adaptability due to higher genetic diversity under selective pressures (such as antifungal agents).

Molecular taxonomy of scopulariopsis-like fungi with description of new clinical and environmental species.

The taxonomy of scopulariopsis-like fungi, comprising numerous human opportunistic species, has recently been reassessed with delineation of the genera Microascus, Pithoascus, Pseudoscopulariopsis, and Scopulariopsis, using morphological data and multilocus sequence analysis based on four loci (ITS, LSU, EF-1α, and TUB). In this study, the same genetic markers were used to investigate a set of clinical and environmental isolates, morphologically identified as Microascus and Scopulariopsis spp. The ingroups of the concatenated phylogenetic tree resolved 41 species clades, with isolates distributed in four main lineages corresponding to the genera Microascus, Pithoascus, Scopulariopsis, and newly established genus Fuscoannellis, typified by Scopulariopsis carbonaria. The new species Microascus chinensis, Microascus onychoides, Microascus pseudolongirostris, Pithoascus lunatus, and Scopulariopsis macurae were described. Microascus trigonosporus var. terreus and Scopulariopsis alboflavescens were found different from M. trigonosporus and Scopulariopsis brevicaulis, respectively. All the species identified in the study, except Fuscoannellis carbonaria and S. macurae, originated from clinical samples, suggesting their potential role in human disease. The use of a four marker combination was demonstrated an efficient and reliable approach to infer phylogenetic relationships among the scopulariopsis-like fungi. Yet, the only genetic marker able to discriminate all species was EF-1α, therefore proposed as a secondary barcode for the identification of these fungi.

In Vitro Triple Combination of Antifungal Drugs against Clinical Scopulariopsis and Microascus Species.

Broth microdilution checkerboard techniques based on the methodology of the Clinical and Laboratory Standards Institute (CLSI) were employed to study the triple antifungal combination of caspofungin, posaconazole, and terbinafine against 27 clinical isolates of Scopulariopsis and Microascus species. Synergy was observed for 26 isolates, whereas antagonism was observed for Scopulariopsis candida in this study.

Polymorphisms of transforming growth factor beta 1 (RS#1800468 and RS#1800471) and esophageal squamous cell carcinoma among Zhuangese population, China.

Epidemiological evidence has shown two polymorphisms (namely RS#1800468G>A and RS#1800471G>C) of transforming growth factor-beta 1 (TGF-ß1) gene may be involved in the cancer development. However, their role in the carcinogenic process of esophageal squamous cell carcinoma (ESCC) has been less well elaborated. We conducted a hospital-based case-control study including 391 ESCC cases and 508 controls without any evidence of tumors to evaluate the association between these two polymorphisms and ESCC risk and prognosis for Zhuangese population by means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS)-PCR techniques. We found that individuals with the genotypes with RS#1800471 C allele (namely RS#1800471-GC or -CC) had an increased risk of ESCC than those without above genotypes (namely RS#1800471-GG, adjusted odds ratio 3.26 and 5.65, respectively). Further stratification analysis showed that this polymorphism was correlated with tumor histological grades and TNM (tumor, node, and metastasis) stage, and modified the serum levels of TGF-ß1. Additionally, RS#1800471 polymorphism affected ESCC prognosis (hazard ratio, 3.40), especially under high serum levels of TGF-ß1 conditions. However, RS#1800468 polymorphism was not significantly related to ESCC risk. These findings indicated that TGF-ß1 RS#1800471G>C polymorphism may be a genetic modifier for developing ESCC in Zhuangese population.